Detection Rate Of Colorectal Cancer Research Articles

Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial

Barium enema (BE) is widely available for diagnosis of colorectal cancer despite concerns about its accuracy and acceptability. Computed tomographic colonography (CTC) might be a more sensitive and acceptable alternative. We aimed to compare CTC and BE for diagnosis of colorectal cancer or large polyps in symptomatic patients in clinical practice. This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for radiological investigation of the colon. Patients were randomly assigned (2:1) to BE or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-diagnosis of colorectal cancer or large (≥10 mm) polyps-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. 3838 patients were randomly assigned to receive either BE (n=2553) or CTC (n=1285). 34 patients withdrew consent, leaving for analysis 2527 assigned to BE and 1277 assigned to CTC. The detection rate of colorectal cancer or large polyps was significantly higher in patients assigned to CTC than in those assigned to BE (93 [7.3%] of 1277 vs 141 [5.6%] of 2527, relative risk 1.31, 95% CI 1.01-1.68; p=0.0390). CTC missed three of 45 colorectal cancers and BE missed 12 of 85. The rate of additional colonic investigation was higher after CTC than after BE (283 [23.5%] of 1206 CTC patients had additional investigation vs 422 [18.3%] of 2300 BE patients; p=0.0003), due mainly to a higher polyp detection rate. Serious adverse events were rare. CTC is a more sensitive test than BE. Our results suggest that CTC should be the preferred radiological test for patients with symptoms suggestive of colorectal cancer. NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomised trial

Colonoscopy is the gold-standard test for investigation of symptoms suggestive of colorectal cancer; computed tomographic colonography (CTC) is an alternative, less invasive test. However, additional investigation after CTC is needed to confirm suspected colonic lesions, and this is an important factor in establishing the feasibility of CTC as an alternative to colonoscopy. We aimed to compare rates of additional colonic investigation after CTC or colonoscopy for detection of colorectal cancer or large (≥10 mm) polyps in symptomatic patients in clinical practice. This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for colonoscopy. Patients were randomly assigned (2:1) to colonoscopy or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-the rate of additional colonic investigation-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. 1610 patients were randomly assigned to receive either colonoscopy (n=1072) or CTC (n=538). 30 patients withdrew consent, leaving for analysis 1047 assigned to colonoscopy and 533 assigned to CTC. 160 (30.0%) patients in the CTC group had additional colonic investigation compared with 86 (8.2%) in the colonoscopy group (relative risk 3.65, 95% CI 2.87-4.65; p<0.0001). Almost half the referrals after CTC were for small (<10 mm) polyps or clinical uncertainty, with low predictive value for large polyps or cancer. Detection rates of colorectal cancer or large polyps in the trial cohort were 11% for both procedures. CTC missed 1 of 29 colorectal cancers and colonoscopy missed none (of 55). Serious adverse events were rare. Guidelines are needed to reduce the referral rate after CTC. For most patients, however, CTC provides a similarly sensitive, less invasive alternative to colonoscopy. NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

Excellent performance of Hemoccult Sensa in organised colorectal cancer screening

BackgroundFaecal occult blood (FOB) testing is the most commonly chosen approach in organised population-based colorectal cancer screening programmes throughout the world. Several FOB tests are available which differ in their test qualities. While immunological tests are gaining popularity due to their lower labour intensive analysis and higher standardisation, they are heat labile and more expensive. We studied the real-life experience of a large population-based, organised, screening programme in Israel which employs FOB testing with Hemoccult Sensa, a guaiac test with increased sensitivity that is similar to that of the immunological tests for cancer. MethodsClalit Health Services is the largest health care provider in Israel. All eligible insurees are actively invited to perform a free-of-charge, home-based, faecal occult blood test, using Hemoccult Sensa. All tests with positive results are followed up and information on colonoscopy, surgical procedures and pathology findings is collected. ResultsDuring an 18month period (July 2007–December 2008) 382,792 FOBT tests (in 325,851 people) were performed by the target population, of them 85% Jews and 15% Arabs. Seven hundred and eighteen colorectal cancers and 2652 adenomas were detected. The overall test positivity rate in repeatedly-tested people was 4.2%. The overall detection rate of colorectal cancer in the subsequent tests was 1.7/1000 reflecting 91% of the expected period-incidence of CRC. 70% of the cancers were detected at stages Duke’s B2 and lower. Left-sided cancers were detected at a significantly better stage than right-sided cancers (P<0.001). Detection rates among Arabs were somewhat lower than among Jews but the screening programme led to a meaningful increase in national incidence rate in this subgroup by detecting tumours that were otherwise asymptomatic. ConclusionThe Clalit organised colorectal cancer screening programme, using low cost Hemoccult Sensa, has reached the targets of very high detection rate of cancers, most of them at low stage while keeping a low positivity rate. This approach demonstrates an efficient field-tested alternative to other, more costly, screening options.

Referral proformas improve compliance to national colorectal 2‐week wait targets: does this affect cancer detection rates?

To facilitate implementation of National Institute for Health and Clinical Excellence (NICE) guidelines for urgent colorectal cancer referral, local cancer networks have promoted the use of standardized proformas in primary care. This clinical audit assessed use of the proforma within the Thames Valley Cancer Network (TVCN) to see whether increased proforma use was associated with higher compliance to NICE guidelines and higher cancer detection rates. All 2-week wait referrals for lower bowel cancer to the six Acute NHS Trusts in the TVCN received during the month of June 2010 were identified, anonymized and analysed in relation to colorectal cancer detection rates. Of the 586 referrals audited, proforma usage varied significantly across the six Acute NHS Trusts from 18% to 96%. Referral letters from primary care had NICE compliance ranging from 30 to 50%. In those which received a referral protocol, 50-90% were NICE compliant. Proforma use was associated with higher cancer detection rates (P = 0.03). These results have wide-ranging implications since they suggest that the adoption of a simple proforma in primary care can improve the effectiveness of referral for suspected cancer.

Screening Colonoscopy from a Large Single Center of Thailand - Something Needs to be Changed?

Results of screening colonoscopy from Western countries reported adenoma detection rates (ADRs) of 30-40% while those from Asia had ADR as low as 10%. There have been limited data regarding screening colonoscopy in Thailand. The objectives of this study were therefore to determine polyp and adenoma detection rates in Thai people, to evaluate the incidence of colorectal cancer detected during screening colonoscopy and to determine the endoscopic findings of the polyps which might have some impact on endoscopists to perform polypectomy. This study was a retrospective electronic chart review of asymptomatic Thai adults who underwent screening colonoscopy in our endoscopic center from June 2007 to October 2010. A total of 1,594 cases were reviewed. The patients had an average age of 58.3 ± 10.5 years (range 27-82) and 55.5% were female. Most of the cases (83.8%) were handled by staff who were endoscopists. A total of 488 patients (30.6%) were reported to have colonic polyps. Left-sided colon was the most common site (45.1%), followed by right-sided colon (36.5%) and the rectum (18%). Those polyps were removed in 97.5% of cases and 88.5 % of the polyps were sent for histopathology (data lost 11.5%). Two hundred and sixty three cases had adenomatous polyps, accounting for 16.5 % ADR. Advanced adenomas were detected in 43 cases (2.6%). Hyperplastic polyps were mainly located distal to the splenic flexure of the colon whereas adenomas were found throughout the large intestine. Ten cases (0.6%) were found to have colorectal cancer. Four advanced adenomas and two malignant polyps were reported in lesions ≤ 5 mm. The polyp detection rate, adenoma detection rate, advanced adenoma detection rate and colorectal cancer detection rate in the screening colonoscopy of Thai adults were 30.9%, 16.5%, 2.6% and 0.6% respectively. Malignant transformation was detected regardless of the size and location of the polyps. Therefore, new technology would play an important role indistinguishing polyps.

Positivity rates and performances of immunochemical faecal occult blood tests at different cut-off levels within a colorectal cancer screening programme

BackgroundImmunochemical faecal occult blood tests have greater sensitivity for colorectal cancer screening than guaiac-based tests; however the number of positive tests required is still under discussion. MethodsA direct comparison of Hemoccult II with two immunochemical quantitative tests (OC-Sensor and FOB-Gold) using a 2-sample strategy was performed in over 30,000 patients undergoing colorectal cancer screening in France. ResultsPositivity ratio between immunochemical tests and Hemoccult II varied between 2.2 (OC-Sensor) and 2.4 (FOB-Gold) for the lowest cut-off value and 1.5–1.4 for the highest cut-off value. The positive predictive value for colorectal cancer was similar for immunochemical tests and Hemoccult II, and significantly higher for immunochemical tests for advanced adenomas. The detection rate of both colorectal cancer and advanced adenomas was higher with immunochemical tests than with Hemoccult II. With the 2-sample strategy and the lowest cut-off value the detection rate of colorectal cancer almost doubled and for advanced adenomas quadrupled. ConclusionFor colorectal cancer screening with immunochemical faecal occult blood tests, an acceptable strategy would be 2-day sampling with at least one positive test at a cut-off between 150 and 200ng/mL (OC-Sensor) and 176 and 234ng/mL (FOB-Gold). Data on the ease of test interpretation and cost-effectiveness now necessary to make definitive choices.

Abstract 3572: Methylated gene marker levels in stool: effects of demographic, drug, and body mass and other patient characteristics

Abstract Aberrantly methylated genes represent attractive and broadly informative markers for colorectal cancer (CRC). As demographics, numerous ingestants, environmental exposures, and obesity variably influence both gene methylation rates and CRC incidence, it is important to understand the effects of such covariates on the clinical performance of CRC screening tests that incorporate assay of methylated gene markers. Based on a recent multicenter study (Ahlquist et al. Gastroenterology 2012 (in press)), stool assay of carefully selected methylated gene marker candidates (NDRG4, BMP3, vimentin, TFPI2), alone or in combination, yield high detection rates of both CRC and large adenomas. Aim: To assess the impact of demographic, exposure, body mass, and other patient variables on stool levels of the above 4 methylated gene markers. Methods: We studied buffered stools collected within 3 years of a normal colonoscopy from 500 patients undergoing average-risk screening or polyp surveillance (median age 64 (range 44-85); 53% women). Upon receipt, stools were promptly homogenized, aliquoted, and frozen at –80°C. On supernatants from thawed/spun aliquots, target genes were purified by hybrid capture, bisulfite treated, and assayed using the analytically-sensitive QuARTS method (quantitative allele-specific real-time target and signal amplification), as described (above citation). The reference gene β-actin was assayed along with methylation of NDRG4, BMP3, vimentin, TFPI2. Log-converted data were normalized to allow comparison of effects between markers, and effect size was expressed as % change relative to standard deviation for each marker (standardized relative change (SRβ)). Results: The only patient characteristic that significantly influenced all methylated marker levels in stool was age (p&amp;lt;0.0001 for each marker); SRΔ was greatest with TFPI2 at +91.3 (p&amp;lt;0.001 vs other markers), least with BMP3 at +29.7 (p&amp;lt;0.001 vs others), and intermediate with vimentin at +46.0 and NDRG4 at +45.1. In contrast to methylation markers, levels of β-actin did not change across age. The other demographic variables of sex, race, and geographic residence had no effect on methylation markers. Marker levels were also not affected by exposure variables (smoking, alcohol consumption, or analgesic use), by family history of CRC or polyps, or by personal history of polyps. Finally, neither overweight status (n=176) nor obesity (n=148) had an effect on marker levels. Conclusions: Age significantly affects stool levels of tumor-associated methylated gene markers in colonoscopy-normal patients, and the degree of this age effect differs across markers. In contrast, other key patient variables had no effect on stool marker levels. Comment: Optimal use of these methylation markers for stool screening of CRC may require age-adjustment of normal cutoff levels to maximize test specificity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3572. doi:1538-7445.AM2012-3572

Combined Fecal Transferrin Test and Immuno Fecal Occult Blood Test for Detecting Colorectal Cancer and Advanced Adenoma in Asymptomatic and Symptomatic Populations

Recent proteomic studies identified Transferin (TF) as a potential colon cancer biomarker. A dipstick TF test similar to Immuno Fecal Occult Blood Test (IFOBT) was developed, and an initial study showed the TF test had compatible performance characteristics for detecting colon cancer and adenoma. The goal of this study was to evaluate the efficacy of the combination of TF and IFOBT for detecting advanced adenomas and cancer in asymptomatic and symptomatic populations. A total of 1,943 healthy subjects (asymptomatic group) and 201 subjects with various gastrointestinal symptoms (symptomatic group) were recruited for the study. For asymptomatic subjects, one fecal sample was collected for concurrent TF and IFOBT testing. Colonoscopy was performed for individuals positive for either TF or IFOBT. For the symptomatic subjects, each individual underwent TF, IFOBT, and colonoscopy simultaneously. For asymptomatic group, 1,737 individuals tested for TF and IFOBT, 251 subjects (14.5%) showed either TF or IFOBT positivity. Colonoscopy was performed for 193 of the 251 individuals. A total of 3 colorectal cancers and 43 advanced adenomas were detected. Combination of the two tests (either/or) significantly increased the detection rate for colorectal cancers and advanced adenomas compared to IFOBT alone (2.6% vs. 1.6%, P=0.034). In the symptomatic group, the combined test also significantly increased the sensitivity for detecting advanced adenomas and cancer than that of IFOBT alone (77.9% vs. 55.9%, P=0.006), but with decreased specificity (42.1% vs 63.9%, P=0.005). Combined TF and IFOBT test increased the detection rate of colorectal adenoma and cancer in both asymptomatic and symptomatic populations.

Audit of adherence to GI screening recommendations for Lynch Syndrome Patients

There is clear evidence documenting the morbidity and mortality benefit of regular colonoscopy surveillance in reducing the high risk of primary and metachronous colorectal cancers associated with Lynch Syndrome (LS) (Jarvinen et al. 2000). The Australian NHMRC guidelines (2005) recommend LS patients undergo a colonoscopy every 1-2 years (NHMRC 2005). At Peter Mac yearly colonoscopy screening is usually advised for LS patients. The long term adherence rate to colonoscopy in LS patients as reported in the literature is between 60-88% (Stoffel et al 2010, Wagner et al 2005). Some factors have been associated with inadequate LS patient screening adherence including lack of sedation, inappropriate advice from managing doctors, financial costs, embarrassment and lack of patient time (Bleiker et al 2005). Whilst not studied, some of these factors may also contribute to a phenomenon known as ‘screening fatigue’, whereby after one or more normal screening procedures patients begin to attend less frequently for the recommended screening procedures. At the Peter Mac patients and their managing doctors are given GI screening recommendations by the FCC when the patient receives their gene mutation results. However, it is unclear whether LS patients continue to follow the GI screening advice set out by an FCC over time and whether there is any evidence that ‘screening fatigue’ exists. Furthermore it is unknown whether differences regarding the frequency of colonoscopy offered/performed, adherence to colonoscopy or quality of endoscopy exist for patients who participate in a high risk GI management clinic versus those who are screened by endoscopists in generalist community based settings. The FCC at Peter Mac undertook an audit of the GI screening practices of 74 confirmed Lynch Syndrome gene mutation carrier patients from 2006-2010. Of these patients 27 participate in a high risk GI management clinic where they receive their GI screening. The additional 47 patients have GI screening conducted through either private endosocopy clinics or at public hospitals. This work will; ❖ Provide a clinical description of our population of LS patients ❖ Describe the rate of adherence to recommended GI screening overtime. This is assessed by comparing the screening practices undertaken with the recommendations provided by the FCC at the time of their gene test result. We will also present data about whether updates of screening recommendations by our FCC were acted upon by patients/their managing doctors. ❖ Assess for evidence of ‘screening fatigue’ ❖ Compare rates of adherence to GI screening practices between patients attending GI high risk management clinics versus patients attending for GI screening in community settings ❖ Describe the overall colorectal polyp and GI cancer detection rate ❖ Use colorectal polyp detection also a measure of quality of colonoscopy We will make some suggestions for further research particularly into interventions that may improve adherence to GI screening advice for a population of LS patients.

FIT to be Tried

FIT to be Tried

Latest Generation, Wide-Angle, High-Definition Colonoscopes Increase Adenoma Detection Rate

Improvements to endoscopy imaging technologies might improve detection rates of colorectal cancer and patient outcomes. We compared the accuracy of the latest generation of endoscopes with older generation models in detection of colorectal adenomas. We compared data from 2 prospective screening colonoscopy studies (the Berlin Colonoscopy Project 6); each study lasted approximately 6 months and included the same 6 colonoscopists, who worked in private practice. Participants in group 1 (n = 1256) were all examined by using the latest generation of wide-angle, high-definition colonoscopes that were manufactured by the same company. Individuals in group 2 (n = 1400) were examined by endoscopists who used routine equipment (a mixture of endoscopes from different companies; none of those used to examine group 1). The adenoma detection rate was calculated on the basis of the number of all adenomas/number of all patients. There were no differences in patient parameters or withdrawal time between groups (8.0 vs 8.2 minutes). The adenoma detection rate was significantly higher in group 1 (0.33) than in group 2 (0.27; P = .01); a greater number of patients with least 1 adenoma were identified in group 1 (22.1%) than in group 2 (18.2%; P = .01). A higher percentage of high-grade dysplastic adenomas were detected in group 1 (1.19%) than in group 2 (0.57%), but this difference was not statistically significant (P = .06). The latest generation of wide-angle, high-definition colonoscopes improves rates of adenoma detection by 22%, compared with mixed, older technology endoscopes used in routine private practice. These findings might affect definitions of quality control parameters for colonoscopy screening for colorectal cancer.

Colonoscopy after Streptococcus bovis Bacteremia: Do We Need More Data?

Purpose:Streptococcus bovis (SB) is a group D non- enterococcal Streptococcus; an association between SB bacteremia (SBB) and colorectal cancer (CC)/adenomatous polyps(AP) has been established and colonoscopy is considered mandatory after the diagnosis. The knowledge however about the true pathophysiologic mechanism is lacking and adenomatous polyps are frequent in general population over 50. The aim of the study was to investigate the prevalence of CC/AP in SBB patients. Methods: The study was made on 26 consecutive patients (8 women, 18 men, medium age at diagnosis 63.3 yrs, range 49-78 yrs) who had positive hemocolture for SB (Group A). Complete colonoscopy and biopsies or polypectomy were performed in all patients. In the same way colonoscopy was made on 26 consecutive asymptomatic patients(6 women, 20 men, medium age 58.1 yrs range 49-69) as a control group (Group B). Data were analysed by Fisher's exact test. Results: In Group A, 14 patients (53.8%) had neoplastic lesions (12 AP = 46.1% and 2, CC = 7.7%); in Group B 8 patients had AP (30.7%). No patient had CC. No statistical significance was found between the two groups. (p= 0.16) Conclusion: The study was made on small groups of patients and the medium age of Control Group was 5 years lower than Group A. The detection rate of CC or AP in SBB patients is higher than expected but the differences between the two groups are not statistically significant. The reasons of the association between SB infection and colon neoplasia (in particular with non ulcerated lesions) are still not clear. At the moment colonoscopy should be recommended after the diagnosis of SBB but more data might be needed.

Epidemiological study of colorectal adenoma and cancer in symptomatic patients in China between 1990 and 2009

The best cure for colorectal cancer (CRC) lies on its early diagnosis and treatment. We aimed to provide the epidemiological features of advanced colorectal adenoma (A-CRA) and CRC in symptomatic patients and to determine whether the incidences of A-CRA and CRC increased simultaneously in China between 1990 and 2009. A total of 157,943 patients who had undergone a colonoscopy from 1990 to 2009 were enrolled, of which 6,777 patients had A-CRA and 3,503 had CRC. They were compared with controls in a stratified analysis. The detection rates of A-CRA and CRC in the 1990s and 2000s were also compared. The detection rate of A-CRA increased 1.88-fold over the two decades, while that of CRC increased 0.66-fold. The percentages of patients with A-CRA and CRC who were elder than 50 years were significantly higher in the 2000s than those in the 1990s (P = 0.000). The changes of location of A-CRA and CRC during the two decades indicated a shift of lesions from the distal colon to proximal colon. There was a significant increase in detection rate of A-CRA in the 2000s, but CRC did not increase at a similar speed. Our results indicated that the early detection and removal of colorectal adenoma in symptomatic patients might decrease the incidence of CRC.

Detection of TFPI2 methylation in the serum of colorectal cancer patients

We examined whether TFPI2 methylation can be used as a molecular marker for colorectal cancers by detecting TFPI2 methylation in colorectal cancer patients’ sera by using quantitative methylation-specific polymerase chain reaction (qMSP). The qMSP analysis showed that 39 of 215 (18%) patients exhibited TFPI2 methylation in their serum DNA, suggesting that TFPI2 methylation frequently existed in colorectal cancer patients’ sera. After completion of qMSP analysis, clinicopathological data were correlated with molecular data. TFPI2 methylation was significant in the sera of patients with large ( p = 0.0022), poorly differentiated carcinoma ( p = 0.0164), deep invasion ( p = 0.0002), lymph node metastasis ( p = 0.0147), or distant metastasis ( p < 0.0001). Moreover, TFPI2 methylation was observed more frequently according to the progression of TNM stage, suggesting that serum TFPI2 methylation could be detected more easily in patients with advanced colorectal cancer. We also examined whether serum TFPI2 methylation would be useful in the detection of colorectal cancer, compared to the conventional tumor markers. Detection rates of colorectal cancer using the tumor markers TFPI2 methylation, CEA and CA19-9, in the serum were 18%, 33%, and 17%, respectively. In cases where we combined all three markers, the detection rate was 42%. High sensitivity of qMSP enables detection of smaller amounts of serum tumor DNA. In principle, the methylation status of a primary tumor is not required in advance to detect circulating tumor DNA, suggesting the potential of qMSP as a cancer screening method.

Abstract 3174: Colorectal cancer specific host response signatures achieved by next generation sequencing and multiplex RT-qPCR

Abstract Background: colorectal cancer (CRC) develops over a period of several years and is often preceded by adenoma formation. Detection rates for colorectal adenoma and early CRC, however, are unsatisfactory due to low compliance towards invasive screening procedures such as colonoscopy. There is a large unmet screening need calling for an accurate, non invasive and cost effective test to screen for early neoplastic and preneoplastic colorectal lesions. We developed a screening test aimed at detecting precancerous lesions and CRC at early stages, based on a multigene expression profiling on peripheral blood mononuclear cells (PBMC). Methods: 92 colonoscopy screened subjects served as a training set. Colonoscopy revealed 21 patients had CRC, 30 adenomas larger than 1cm and 41 had no detectable lesions. 16 mL of blood was collected from each individual and PBMC were purified using Vacutainer® CPT tubes (Becton Dickinson). Total RNA was extracted and a whole genome expression analysis by digital gene expression TAG profiling (Illumina) was performed on a subset of these 92 subjects. Deep sequencing generated on average 1.5 million reads per sample and they matched to 20288 different transcripts. Different univariate and multivariate statistical methods were then applied in order to find genes differentially expressed between control, adenoma and CRC (pvalue &amp;lt;0.05). 45 candidate genes discovered with TAG profiling were then analytically validated using a multiplex RT qPCR methodology. All candidate genes were normalized with a stable normalization strategy in order to obtain comparable results across assays. An additional set of 57 candidate genes was also added based on literature review and validated using the multiplex RT qPCR methodology. Multiple statistical methods were applied on the normalized PCR data and 43 biomarkers, with significant p-value (&amp;lt;0.01) for most of the methods, were selected. Two distinct molecular signatures were derived from the normalized biomarker combinations based on penalized logistic. Results: a validation set was defined using random resampling (bootstrapping method), leading to the separation of individuals without lesion from those with CRC (Se 70%, Sp 94%, AUC 0.89) and from those with adenoma larger than 1cm (Se 67%, Sp 87%, AUC 0.80). In addition, as a test set, the organ and disease specificity of these signatures was confirmed by means of patients with other cancer types and inflammatory bowel diseases. Conclusion: Next generation sequencing is a powerful research tool to define specific signatures for precancerous and early cancerous lesions when coupled to multiplex RT qPCR and normalized with specific reference genes. A prospective, multi-centric, pivotal study is underway in order to validate these results in a larger cohort. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3174. doi:10.1158/1538-7445.AM2011-3174

Biomarkers for Colorectal Cancer

Colorectal cancer (CRC) is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy significantly improves the detection rate of CRC, but the examination is expensive and inconvenient. Therefore, we need novel biomarkers that are non-invasive to enable us to detect CRC quite early. A number of validation studies have been conducted to evaluate genetic, epigenetic or protein markers for identification in the stool and/or serum. Currently, the fecal occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics will lead to the discovery of novel non-invasive biomarkers.

A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test, despite lower compliance rate. A prospective, controlled, feasibility study

Immunochemical fecal occult blood test (FIT) is a new colorectal cancer (CRC) screening method already recommended by the American screening guidelines. We aimed to test the feasibility of FIT as compared to guaiac fecal occult blood test (G-FOBT) in a large urban population of Tel Aviv. Average-risk persons, aged 50-75 years, were offered FIT or G-FOBT after randomization according to the socioeconomic status of their clinics. Participants with positive tests underwent colonoscopy. Participants were followed through the Cancer Registry 2 years after the study. Hemoccult SENSA™ and OC-MICRO™ (three samples, 70 ng/ml threshold) were used. FIT was offered to 4,657 persons (Group A) and G-FOBT to 7,880 persons (Group B). Participation rate was 25.9% and 28.8% in Group A and B, respectively (p < 0.001). Positivity rate in Group A and B was 12.7% and 3.9%, respectively (p < 0.001). Cancer found in six (0.49%) and eight (0.35%) patients of Group A and B, respectively (NS). Cancer registry follow-up found missed cancer in five (0.22%) cases of Group B and none in Group A (NS). The sensitivity, specificity, negative and positive predictive value for cancer in Group A and B were 100%, 85.9%, 100%, 3.9% and 61.5%, 96.4%, 99.8%, 9.1%, respectively. There was increased detection of advanced adenomatous polyp (AAP) by FIT, irrespective of age, gender, and socioeconomic status (Per Protocol: odds ratio 2.69, 95% confidence interval 1.6-4.5; Intention to Screen: odds ratio 3.16, 95% confidence interval 1.8-5.4). FIT is feasible in urban, average-risk population, which significantly improved performance for detection of AAP and CRC, despite reduced participation.

Colonoscopy for Colorectal Cancer Screening Above Age 75: Outcomes in Symptomatic African American and Hispanic Adults

US Preventive Services Task Force recommends against routine screening for colorectal cancer (CRC) in adults above 75years of age. Considerations to support screening in an individual patient are not clearly described. There is limited data to support recommendations in African American (AA) and Hispanics population. We reviewed records of 568 inpatient colonoscopies carried out at our Mt. Sinai Hospital Medical Center, Chicago during 2006-2008 for symptomatic adults ≥75years of age. Subjects with previous normal screening colonoscopies and presence of one or more "generally indicated" indications as per American Society for Gastrointestinal Endoscopy guidelines were included in the study. A total of 155 adults (mean age, 81.8years; 29% males and 71% females; 83.8% AAs and 16.1% Hispanics) met the inclusion criteria. Seventy-nine percent had one previous colonoscopy, whereas 21% of the patients had two or more previous colonoscopies. Common indications for a repeat colonoscopy were anemia 69.7%, hematochezia 39.4%, and fecal occult blood 19.4%. Colonoscopy was completed to the cecum in 65.2% of the subjects. Advanced adenomas/cancers were found in 15/155 (9.7%) colonoscopies. CRC detection rate was 14/155 (9%), of which 9/14 (75%) were staged III/IV. Two (1.3%) patients had complications which resolved conservatively. Symptomatic AAs and Hispanics ≥75 have a high incidence of CRC despite a previous normal colonoscopy. Presence of male sex, new onset anemia and hematochezia, and longer colonoscopy intervals are associated with CRC detection on colonoscopy. The detection of advanced cancer and high comorbidity/low life expectancy limit the benefit of CRC detection.

Effectiveness of the Immunofecal Occult Blood Test for Colorectal Cancer Screening in a Large Population

Guaiac tests are the most widely used tests to detect colorectal cancer (CRC). However, their sensitivity is relatively low and results may be affected by various factors. Immunofecal occult blood test (IFOBT) is specific for human hemoglobin and does not require dietary restrictions. The aim of this study was to evaluate the effectiveness of IFOBT for the screening of precancerous lesions and CRC. From July 2006 to June 2007, IFOBT was performed on 5,919 adults who received periodic health examinations in our hospital. The positive cases were examined by colonoscopy and a double-contrast barium enema. Diagnosis was confirmed by histopathological analysis. Positive IFOBT was detected in 314 of 5,919 cases (5.30%). Further examinations were made in 264 IFOBT-positive cases. Of these, 116 cases with colorectal cancer (16 cases) or precancerous lesions (94 cases with colorectal adenomatous polyps and 6 cases with active ulcerative colitis) were detected. The total detection rate of CRC and precancerous lesions was 43.94% (116/264). TNM classification of 16 CRC cases was as follows: TNM I in eight cases (50.00%), TNM II in seven cases (43.75%) and TNM III in one case (6.25%), indicating IFOBT can detect CRC in the early stages. Regular IFOBT can detect precancerous lesions and CRC in early stages and can thus reduce mortality from CRC.

Screening of high-risk group with colorectal cancer

To measure the rate of high-risk group and the detection rate of colorectal cancer (CRC) in communities in Guangdong province and to provide scientific rationales for formulating mass screening plans in high-risk group. Mass survey was conducted by questionnaire combined fecal occult blood test (FOBT) in Huizhou region, Guangdong Province, to sort out the high-risk population of CRC. Then the high-risk population was screened by colonoscopy and pathology to identify CRC. The differences were compared by direct expenditure which was used to calculate screening cost. A total of 68,953 people were surveyed. There were 940 people in high-risk group (detection rate: 1.36%), 3118 in immunity FOBT positive group (detection rate: 4.52%), Merging aforementioned two groups, there were 3870 in population at risk (detection rate: 5.61%). The CRC detection rate in high-risk group, immunity FOBT positive group, population at risk and average-risk group was 506.3/10(5), 314.3/10(5), 315.9/10(5) and 17.7/10(5) respectively. The positive predictive value of CRC screening scheme by high-risk group questionnaire-colonoscopy was 0.43% while CRC screening scheme by FOBT-colonoscopy 0.22%. In terms of direct expenditure of CRC per case in high-risk group and immunity FOBT positive group was 47,834.5 yuan and 82,303.6 yuan. The latter was 1.7 times than that of the former. The scheme of questionnaire combined FOBT for CRC is an effective way in mass survey. The scheme by high-risk group questionnaire-colonoscopy has a much better cost-effectiveness than that of the scheme by FOBT-colonoscopy so that it should be one of the preferred methods for individual screening in high-risk group.