Non-advanced Adenomas Research Articles

Expected long-term impact of the German screening colonoscopy programme on colorectal cancer prevention: Analyses based on 4,407,971 screening colonoscopies

AimEndoscopy based screening programmes for colorectal cancer (CRC) are being implemented in an increasing number of countries. In Germany, screening colonoscopy at age 55 or older has been offered since the end of 2002. We aimed to estimate the long-term impact of this offer on CRC prevention. MethodsWe estimated numbers of prevented CRC cases by expected age and year of their (prevented) occurrence over four decades (2005–2045) by four state Markov models (non-advanced adenoma, advanced adenoma, preclinical CRC, clinically manifest CRC). Estimates are based on screening colonoscopies reported to the German screening colonoscopy registry in 2003–2012 (N=4,407,971), transition rates between the four states and general population mortality rates. ResultsNumbers of prevented clinically manifest CRC cases are projected to increase from <100 in 2005 to approximately 6500 in 2015, 12,600 in 2025, 15,400 in 2035 and 16,000 in 2045, compared to approximately 58,000 incident cases observed in 2003. The annual number of prevented cases is expected to be higher among men than among women and to strongly vary by age. The vast majority of prevented cases would have occurred at age 75 or older. ConclusionsDespite modest participation rates, the German screening colonoscopy programme will lead to substantial reductions in the CRC burden. The reductions will be fully disclosed in the long run only and predominantly affect numbers of incident cases above 75years of age. Screening offers would need to start at younger ages in order to achieve more effective CRC prevention at younger ages.

783 Menopausal Hormone Therapy Is Associated With Increased Risk of Lower Gastrointestinal Bleeding

G A A b st ra ct s significant differences in adenoma detection at follow up. Methods: Data were collected prospectively in a randomized placebo controlled chemoprevention trial (Vitamin D/Calcium) from May 2004 to Nov 2008. Subjects (45-75 yrs) had at least 1 colorectal adenoma removed and none remaining after complete colonoscopy. Trial eligibility required that subjects have either 3 yr or 5 yr follow up, as determined by the endoscopist at the qualifying exam. Subjects with 1 to 2 small non-advanced adenomas on baseline were included. Data collected included patient (age, gender, race/ethnicity, family history, BMI, smoking, study center), baseline endoscopist (age, gender, specialty), and baseline and follow up exam findings. Comparisons were made between subjects with recommended follow-up of 3 vs 5 yrs. A t-test was used to compare continuous variables while Chi Square was used to compare proportions or categorical data. We fit a generalized linear model to evaluate predictors of 3 vs. 5 yr surveillance interval. We also used generalized linear models to compute risk ratios for outcome findings at the follow up exam (e.g. adenoma, advanced adenoma) comparing the recommended 5 to 3 yr intervals. Results: Of the 2259 enrolled subjects, 1560 had LRAs on baseline colonoscopy and had a follow up exam during the trial. 38.1 % (n=594) of the subjects had a 3 yr recommended follow up interval. There were no differences between the groups with regards to subject age, gender, smoking, activity level, BMI, ETOH, bowel prep, endoscopist age or gender. After adjustment for subject age, gender and clinical center, significant factors contributing to exams being recommended at a 3 vs a 5 yr interval were family history of CRC, having 2 adenomas on baseline, and having serrated lesions at baseline (Table 1). There were no significant differences in exam findings on follow up for the 3 vs 5 yr group (Table 2). Conclusions: Endoscopists frequently recommend shorter intervals for LRAs than those recommended by guidelines. Both clinical and endoscopic factors such as family history and the number of serrated lesions found appear to influence the decision making process. However neoplasia detection was similar between the two groups and thus the results support current surveillance guidelines that recommend follow up intervals of at least 5 yrs for LRAs. Table 1. Factors contributing to exam being recommended at a shorter interval (3 versus 5 years)

Multi-center colonoscopy quality measurement utilizing natural language processing.

An accurate system for tracking of colonoscopy quality and surveillance intervals could improve the effectiveness and cost-effectiveness of colorectal cancer (CRC) screening and surveillance. The purpose of this study was to create and test such a system across multiple institutions utilizing natural language processing (NLP). From 42,569 colonoscopies with pathology records from 13 centers, we randomly sampled 750 paired reports. We trained (n=250) and tested (n=500) an NLP-based program with 19 measurements that encompass colonoscopy quality measures and surveillance interval determination, using blinded, paired, annotated expert manual review as the reference standard. The remaining 41,819 nonannotated documents were processed through the NLP system without manual review to assess performance consistency. The primary outcome was system accuracy across the 19 measures. A total of 176 (23.5%) documents with 252 (1.8%) discrepant content points resulted from paired annotation. Error rate within the 500 test documents was 31.2% for NLP and 25.4% for the paired annotators (P=0.001). At the content point level within the test set, the error rate was 3.5% for NLP and 1.9% for the paired annotators (P=0.04). When eight vaguely worded documents were removed, 125 of 492 (25.4%) were incorrect by NLP and 104 of 492 (21.1%) by the initial annotator (P=0.07). Rates of pathologic findings calculated from NLP were similar to those calculated by annotation for the majority of measurements. Test set accuracy was 99.6% for CRC, 95% for advanced adenoma, 94.6% for nonadvanced adenoma, 99.8% for advanced sessile serrated polyps, 99.2% for nonadvanced sessile serrated polyps, 96.8% for large hyperplastic polyps, and 96.0% for small hyperplastic polyps. Lesion location showed high accuracy (87.0-99.8%). Accuracy for number of adenomas was 92%. NLP can accurately report adenoma detection rate and the components for determining guideline-adherent colonoscopy surveillance intervals across multiple sites that utilize different methods for reporting colonoscopy findings.

Differential expression of circulating microRNAs according to severity of colorectal neoplasia

There is a need to develop a colorectal cancer (CRC) screening test that is noninvasive, cost effective, and sensitive enough to detect preneoplastic lesions. This case-control study examined the feasibility of using circulating extracellular microRNAs (miRNAs) to differentiate a spectrum of colorectal neoplasia of various severity and hence for early detection of colorectal neoplasia. Archived serum samples of 10 normal controls and 31 cases, including 10 with nonadvanced adenoma, 10 with advanced adenoma, and 11 with CRC, were profiled for circulating miRNAs using next-generation sequencing. Multiple linear regression, adjusting for age, gender, and smoking status, compared controls and the 3 case groups for levels of 175 miRNAs that met stringent criteria for miRNA sequencing analysis. Of the 175 miRNAs, 106 miRNAs were downregulated according to severity of neoplasia and showed a relative decrease in the expression from controls to nonadvanced adenoma to advanced adenoma to CRC (Ptrend<0.05). Pairwise group comparisons showed that 39 and 80 miRNAs were differentially expressed in the advanced adenoma and CRC groups compared with the controls, respectively. Differences in miRNA levels between the nonadvanced adenoma group and controls were modest. Our study found that expression of many miRNAs in serum was inversely correlated with the severity of colorectal neoplasia, and differential miRNA profiles were apparent in preneoplastic cases with advanced lesions, suggesting circulating miRNAs could serve as potential biomarkers for CRC screening.

Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization.

Studies linking cholesterol levels to the development of colorectal neoplasia are inconsistent, and Mendelian randomization has been suggested as a way to help avoid problems with confounding and reverse causation. We genotyped individuals who received a colonoscopy at Group Health (1998-2007) for 96 of 102 single-nucleotide polymorphisms identified by the Global Lipids Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non-advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free controls. All had at least one available pre-colonoscopy lipid measurement from electronic records maintained by Group Health. Advanced adenoma cases were more likely than controls to have higher pre-colonoscopy zenith low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (odds ratio, OR per 20mg/dL LDL increase: 1.16, 95% confidence interval, CI 1.03-1.30; per 40mg/dL TG increase: 1.09, 1.03-1.16; and per 20mg/dL TC increase: 1.09, 1.02-1.18). For these traits, genotype-polyp ORs using weighted allele scores were not statistically significant (OR per increase in score scaled to a 20mg/dL LDL increase: 1.17, 0.78-1.75; a 40mg/dL TG increase: 1.12, 0.91-1.38; a 20mg/dL TC increase: 0.99, 0.71-1.38). Cholesterol levels may be associated with advanced adenomas, but larger studies are warranted to determine whether this association can be attributed to genetics.

Prevalence of advanced colorectal neoplasm after kidney transplantation: surveillance based on the results of screening colonoscopy.

The aim of this study was to determine whether the prevalence of advanced colorectal neoplasms increases in kidney transplant recipients and to define the appropriate duration for surveillance colonoscopy after kidney transplantation (TPL). Our study consisted of 248 kidney transplant patients who underwent a colonoscopy at Seoul National University Hospital from 1996 to 2008. For each patient, two or more age- and sex-matched controls were identified from a population of asymptomatic individuals. Twenty (8.1 %) patients had advanced colonic neoplasms, including colorectal cancers (four patients, 1.6 %), after kidney TPL. A case-control study showed that the odds of advanced colonic neoplasms occurring in TPL patients were 2.3 times greater than in the matched subjects. In addition, TPL patients 50 years of age or older had an approximate 5.4-fold higher risk of developing advanced neoplasms than did the matched subjects (OR 5.370; 95 % CI 2.543-11.336; P < 0.001). Age and history of advanced neoplasms were associated with an increased risk of developing advanced neoplasms after TPL. The 5-year cumulative incidence rate of advanced neoplasms was 3.6 % in the 82 patients with normal or non-advanced adenomas detected via screening colonoscopy before TPL. Colonoscopy is recommended for patients before and after kidney TPL, especially for those 50 years of age or older. Colonoscopy surveillance after TPL is warranted strictly according to the baseline risk stratification.

Escherichia coli strains of phylogenetic group B2 and D and bacteriocin production are associated with advanced colorectal neoplasia.

BackgroundColorectal cancer (CRC) is the 3rd most common cancer worldwide and the Czech Republic has the 6th highest incidence of CRC worldwide. Large intestinal microbiota play in its etiopathogenesis important role. Bacteriocins are proteins, produced by bacteria from the Enterobacteriaceae family. The aim of our prospective study was to assess the colonization of large intestinal mucosa by Escherichia coli strains and to investigate their bacteriocin production.MethodsA total of 30 consecutive patients with colorectal adenoma, CRA (17 men, 13 women, aged 39–79, mean age 63 ± 9), 30 patients with CRC (23 men, 7 women, aged 38–86, mean age 67 ± 11) and 20 healthy controls (9 men, 11 women, age 23–84, mean age 55 ± 15) were enrolled into prospective study. Mucosal biopsies were taken in the caecum, transverse colon and rectum during pancolonoscopy. Microbiological culture, isolation and identification of bacteria followed. Bacteriocin production was assessed by growth inhibition of indicator strains E. coli K12-Row, E. coli C6 (phi), and Shigella sonnei 17. Identification of bacteriocin-encoding determinants and E. coli phylogroups was performed using PCR methods.ResultsA total of 622 strains were isolated and further investigated. A significantly higher frequency of simultaneous production of colicins and microcins was revealed in the group of patients with CRC, when compared to patients with CRA, p = 0.031. A significantly higher frequency of E. coli phylogroup D was found in patients with CRC, when compared to controls, p = 0.044. A significantly higher prevalence of bacteriocinogeny was confirmed in patients with advanced adenoma when compared to patients with non-advanced adenoma, p = 0.010. Increasing bacteriocinogeny was associated with an increasing stage of CRC (assessed according to TNM classification). Either E. coli phylogroup B2 or E. coli phylogroup D were isolated in biopsies of patients with right-sided CRC. A statistically higher incidence of E. coli phylogroup B2 was found in patients with right-sided CRC when compared to patients with left-sided CRC, p = 0.028.ConclusionsLarge intestinal mucosa of patients with more advanced colorectal neoplasia is colonized with more virulent strains of E. coli and higher production of bacteriocins is observed in these patients when compared to those with less advanced colorectal neoplasia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0733-7) contains supplementary material, which is available to authorized users.

Long-term risk of colorectal cancer in individuals with serrated polyps

ObjectiveAlthough serrated polyps may be precursors of colorectal cancer (CRC), prospective data on the long-term CRC risk in individuals with serrated polyps are lacking.DesignIn a population-based randomised trial, 12 955...

Evaluation of optimized sequential screening program of colorectal cancer in current China

To evaluate the sensitivity and specificity of optimized sequential screening program of colorectal cancer, and provide evidence for the further optimization of colorectal cancer screening program. Using cluster sampling method, 4 administrative villages were selected from Jiashan county as a census district in 2011 to 2013. Volunteers of 40 to 74 years old in the census were recruited, and tested by both optimized sequential screening (including questionnaire survey and fecal occult blood test) and colonoscopy for colorectal cancer. Sensitivity and specificity of different screening methods were calculated, respectively. A total of 2 607 volunteers took both simultaneously screening and colonoscopy at the same time. 20 colorectal cancer cases, 85 advanced adenoma cases, 271 non-advanced adenomas cases, and 141 non-adenomatous polyps cases were detected. Sensitivity of optimized sequential screening for colorectal cancer, advanced adenomas, and non-advanced adenomas were 70.0% (14/20) , 57.6% (49/85) and 36.5% (99/271) , specificity was 68.7% (1 776/2 587) , 69.2% (1 746/2 522) and 68.9% (1 610/2 336) , respectively. Sensitivity of the fecal occult blood test of colorectal cancer, advanced adenomas and non-advanced adenomas were 70.0% (14/20) , 47.1% (40/85) and 26.6% (72/271), specificity was 79.4% (2 053/2 587), 79.9% (2 014/2 522) and 79.6% (1 860/2 336). The sensitivity of fecal occult blood test and those of optimized sequential screening for colorectal cancer, advanced adenomas was not significant (χ(2) = 0.00, 1.91, all P values > 0.05). Sensitivity of questionnaire survey of colorectal cancer, advanced adenomas and non-advanced adenomas were 10.0% (2/20), 14.1% (12/85), 12.9% (35/271), specificity was 87.6% (2 266/2 587), 87.7% (2 211/2 522), 87.6% (2 046/2 336). There were no significant difference between non-advanced adenomas. The sensitivity of advanced adenomas and non-advanced adenomas showed no significant decline when the following six term were removed from screening programs: chronic diarrhea, chronic constipation, mucus or bloody history, history of chronic appendicitis or appendectomy surgery, chronic cholecystitis or gallbladder surgery, adverse events in the history of life, while the sensitivity of colorectal cancer remained nearly the same 70.0% (14/20), 52.9% (45/85), 31.4% (85/271) (χ(2) = 0.38, 1.61, all P values > 0.05). Current optimized sequential screening programs for colorectal cancer in China have a high sensitivity and specificity. However, further optimization is viable and necessary.

Effects of Metabolic Syndrome and Findings From Baseline Colonoscopies on Occurrence of Colorectal Neoplasms

Metabolic syndrome is associated with increased risk of colorectal neoplasm, but little is known about its effects on the occurrence of neoplasm after colonoscopy. We investigated the effects of metabolic syndrome on the risk of advanced neoplasm after colonoscopy. We performed a prospective study of 4483 subjects age 50 years and older who underwent screening and surveillance colonoscopies as part of an annual health check-up at National Taiwan University Hospital. Baseline demographic data and colonoscopic findings were recorded. Subjects with either advanced adenoma or 3 or more adenomas detected at baseline were classified as high risk; those with fewer than 3 nonadvanced adenomas were classified as low risk; and those without any neoplastic lesions were classified as normal. The cumulative risk of detecting an advanced neoplasm during surveillance colonoscopies (3 and 5 years later) was correlated with risk group and metabolic syndrome. Hazard ratios (HRs) were calculated for occurrence of neoplasm according to baseline colonoscopic findings and clinical risk factors, including metabolic syndrome. Advanced neoplasms were detected during the surveillance colonoscopies in 1.3% of subjects in the normal group and in 2.4% of those in the low-risk group at 5 years, and in 8.5% of subjects in the high-risk group at 3 years. Subjects with metabolic syndrome had a significantly higher risk for subsequent advanced neoplasms (P < .0001). After stratification based on findings from baseline colonoscopies, the risk for neoplasm was significant in the normal (P<.001) and low-risk groups (P= .04), but not in the high-risk group (P=.48). In Cox regression analysis, metabolic syndrome had significant effects on the risk for advanced neoplasms in the normal (HR, 2.07; 95% confidence interval, 1.13-3.81) and low-risk groups (HR, 2.34; 95% confidence interval, 1.01-5.41), but not in the high-risk group. Metabolic syndrome is a significant risk factor for occurrence of an advanced adenoma after a negative or low-risk finding from a baseline colonoscopy. Metabolic syndrome should be considered in risk stratification for surveillance intervals.

Association between serrated polyps and the risk of synchronous advanced colorectal neoplasia in average‐risk individuals

Serrated polyps of the colorectum have distinct histological features and malignant potential. To assess the association between the presence of serrated polyps and synchronous advanced colorectal neoplasia. Among 4989 asymptomatic Chinese individuals aged 50-70years who underwent screening colonoscopy, 281 cases with advanced neoplasia (adenoma ≥1cm, with tubulovillous/villous histology, with high-grade dysplasia, or invasive adenocarcinoma) were compared with 4708 controls without advanced neoplasia for age, sex, smoking history, body mass index, family history of colorectal cancer and the presence of serrated polyps. Independent predictors of advanced neoplasia were determined by multivariate logistic regression analysis. The prevalence of advanced neoplasia and serrated polyps (excluding small distal hyperplastic polyps) was 5.7% and 5.6%, respectively. 3.7% and 0.4% subjects had proximal and large (≥10mm) serrated polyps, respectively. Independent predictors of synchronous advanced colorectal neoplasia were the presence of sessile serrated adenomas (OR: 4.52; 95% CI: 2.40-8.49), proximal serrated polyps (OR: 2.23, 95% CI: 1.38-3.60), large serrated polyps (OR: 59.25; 95% CI: 18.85-186.21), hyperplastic polyps (OR: 1.66; 95% CI: 1.03-2.67), three or more serrated polyps (OR: 4.86; 95% CI: 1.24-19.15) and one or more non-advanced tubular adenomas (OR: 3.58, 95% CI: 2.59-4.96). Detection of proximal, sessile and/or large serrated polyps at screening colonoscopy is independently associated with an increased risk for synchronous advanced neoplasia.

Surveillance colonoscopy in low-risk postpolypectomy patients: Is it necessary?

AimPatients who have had colorectal adenomas removed are at increased risk of developing colorectal cancer in the future. We sought to determine whether surveillance colonoscopy at 5 years in low-risk...

Rare circulating microRNAs as biomarkers of colorectal neoplasia.

BackgroundMicroRNAs (miRNAs) are regulatory RNAs, stable in circulation, and implicated in colorectal cancer (CRC) etiology and progression. Therefore they are promising as early detection biomarkers of colorectal neoplasia. However, many circulating miRNAs are highly expressed in blood cells, and therefore may not be specific to colorectal neoplasia.MethodsWe selected 7 miRNA candidates with previously reported elevated expression in adenoma tissue but low expression in blood cells (“rare” miRNAs), 2 previously proposed as adenoma biomarkers, and 3 implicated in CRC. We conducted a colonoscopy-based case-control study including 48 polyp-free controls, 43 advanced adenomas, 73 non-advanced adenomas, and 8 CRC cases. miRNAs from plasma were quantified by qRT-PCR. Correlations between miRNA expression levels, adjusted for age and sex, were assessed. We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals quantifying the association between expression levels of miRNAs and case groups. We also conducted nonparametric receiver operating characteristic (ROC) analyses and estimated area under the curve (AUC).ResultsmiRNAs with high expression levels were statistically significantly correlated with one another. No miRNAs were significantly associated with non-advanced or advanced adenomas. Strong (ORs >5) and significant associations with CRC were observed for 6 miRNA candidates, with corresponding AUCs significantly >0.5.ConclusionsThese candidate miRNAs, assayed by qRT-PCR, are probably unsuitable as blood-based adenoma biomarkers. Strong associations between miRNAs and CRC were observed, but primarily with miRNAs highly expressed in blood cells. These results suggest that rare miRNAs will require new detection methods to serve as circulating biomarkers of adenomas.

Abstract 554: GPNMB methylation: a new marker of potentially colonic adenoma in African Americans

Abstract Background: Colorectal cancer (CRC) arises from epigenetic and genetic alterations in a stepwise histological progression sequence. Aim: We examined the role of glycoprotein non-metastatic melanoma protein B (GPNMB) gene in normal, adenoma and CRC in African American (AA) patients to elucidate epigenetic drivers of colon oncogenic transformation. Patients and Methods: Methylation status of 13 CpG sites (chr7: 23287345-23287426) in GPNMB gene's promoter, selected from IHM27 array methylation profiling, was analyzed by pyrosequencing in human CRC cell lines (HCT116, SW480, and HT29) as well as paraffin embedded samples with normal (n=20), non-advanced adenoma (NA; n=20), advanced adenoma (AD; n=48), and cancer tissue (n=20). Furthermore, GPNMB expression was analyzed by immunohistochemistry (IHC). Tumor suppressor functions of GPNMB were examined by cell proliferation, migration and invasion assays in HCT116 colon cell line that was stably transfected with a GPNMB cDNA expression vector. In addition, correlations between the methylation status of GPNMB and various clinicopathological features (age, location and sex) were analyzed. Results: GPNMB methylation was lower in normal mucosa compared to CRC samples (4/20 [20%] vs. 19/20 [95%]; P&amp;lt;0.001). AD also had a significantly higher GPNMB methylation frequency than normal colon samples (45/48 [94%] vs 4/20 [20%]; P&amp;lt;0.001). GPNMB was more frequently methylated in AD than in matched normal mucosa from three patients (3/3 [100%] vs 1/3 [33.3%]; P&amp;lt;0.001). Finally, the frequency of GPNMB methylation in NA differs significantly from that in the normal mucosa (16/21 [76%] vs 4/20 [20%]; P0.5). Gender, location, and age were independent of GPNMB methylation. However, there was statistically significant correlation of higher methylation at advanced stages and lower methylation at stage 1 CRCs (P&amp;lt;0.05). In agreement with these findings, GPNMB protein expression decreased in CRC tissues compared with AD and NA colon mucosa, p&amp;lt;.05. GPNMB expression silencing through promoter methylation was evident in AD and CRC. GPNMB overexpression in HCT116 colon cancer cell line decreased cell proliferation [(24h, P=0.026), (48h, P&amp;lt;0.001), and (72h, P=0.007)], invasion (p&amp;lt;.05) and migration compared to the mock-transfected cells (p&amp;gt;.05). Conclusion: Our data indicate a high methylation profile leading to a lower GPNMB expression in adenoma and CRC samples. As such, GPNMB might be useful as a biomarker of adenomas with high carcinogenic potential in African Americans. Citation Format: Hamed Rahi, Tahmineh Haidary, Hassan Brim, Edward L. Lee, Babak Shokrani, H Zhifeng, Peter M. Siegel, Hassan Ashktorab. GPNMB methylation: a new marker of potentially colonic adenoma in African Americans. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 554. doi:10.1158/1538-7445.AM2014-554

Abstract 299: Circulating microRNAs in association with colorectal neoplasia

Abstract Purpose: MicroRNAs (miRNAs) are non-coding regulatory RNAs that are stable in circulation and implicated in the etiology of many cancers including colorectal cancer (CRC). In this study we investigated whether candidate miRNAs could serve as blood-based biomarkers of colorectal adenoma. Methods: We conducted a colonoscopy-based case-control study of men and women ages 50-79; this report includes data from 48 polyp-free controls, 43 advanced adenoma, 73 non-advanced adenomas, and 8 CRC cases. We selected 12 miRNA candidates that are highly expressed in adenoma tissue and have low expression in blood cells, in addition to miRNAs previously reported as biomarkers of adenoma. miRNAs were extracted from stored plasma samples, and copy number assessed with qRT-PCR. Odds ratios (ORs) and area-under-the-curve (AUC) from receiver-operator characteristic curves were estimated to quantify the association between plasma copy-number of these candidate miRNAs and each case group. Results: No miRNA transcripts were associated with risk of adenoma or advanced adenomas, or with an AUC significantly above 0.5 that would indicate usefulness in discriminating either category of adenoma cases from controls. In contrast, statistically significant and strong associations (ORs&amp;gt;5) with CRC were observed for 6 miRNA candidates, with corresponding AUCs significantly greater than 0.5. Conclusions: Our results suggest that these candidate miRNAs, assayed with qRT-PCR, are unlikely to have clinical utility as blood-based screening biomarkers of adenomas. However, strong associations were observed with CRC. Circulating miRNAs may therefore have promise as potential early detection biomarkers to augment current CRC screening methods, but an optimal screening biomarker would detect pre-malignant colorectal adenomas as well as frank CRC. Citation Format: Scott V. Adams, Polly A. Newcomb, Andrea N. Burnett-Hartman, Melissa P. Upton, Lee-Ching Zhu, Margaret Mandelson, John D. Potter, Karen W. Makar. Circulating microRNAs in association with colorectal neoplasia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 299. doi:10.1158/1538-7445.AM2014-299

Abstract 294: Blood lipids, colorectal adenomas, and non-adenomatous polyps: A comparison of associations from clinical measurements and Mendelian randomization

Abstract Background: Numerous studies have assessed associations between lipid levels and risk of colorectal neoplasia, but findings have been inconsistent. Recent genetic studies have identified &amp;gt;100 loci associated with lipid levels. Knowledge of the magnitude and direction of genetic effects permits evaluation of allele scores that can serve as proxies for phenotypes. Methods: We collected information on blood lipids as part of a colonoscopy study among enrollees, ages 25-79, of Group Health, a large healthcare system in Washington State. Low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) measurements were extracted from electronic medical records for 98% of participants. For each participant, we identified the highest LDL, TG, and TC measurement (zenith) and lowest HDL measurement (nadir) prior to colonoscopy. All participants were genotyped for 96 single-nucleotide polymorphisms (SNPs) identified by the Global Lipids Genetics Consortium. For each lipid trait, we estimated 3 associations: 1) phenotype-polyp odds ratios (OR) with 95% confidence intervals (CI) comparing non-advanced adenoma cases to controls, advanced adenoma cases (≥10 mm in diameter, with villous components, or high-grade dysplasia) to controls, and non-adenomatous polyp cases to controls from polytomous logistic regression; 2) genotype-phenotype associations from linear regression; and 3) genotype-polyp ORs from two-stage linear-logistic regression. Results: In total, 1,791 participants had information on phenotype and genotype (518 non-advanced adenoma cases, 139 advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free controls). Individuals with advanced adenomas were more likely than controls to have higher LDL and TG (adjusted OR per 20 mg/dL increase in zenith LDL: 1.16, CI 1.03-1.30 and OR per 40 mg/dL increase in zenith TG: 1.09, 1.03-1.16). Associations from allele scores were in the same direction (OR per increase in allele score scaled to be comparable to a 20 mg/dL LDL increase: 1.17, CI 0.78-1.75, and OR per increase in allele score scaled to be comparable to a 40 mg/dL TG increase: 1.12, 0.91-1.38). SNPs most strongly related to phenotype, however, were not associated with polyps, and SNPs that were, including variants of NAT2, MC4R, and APOE, may function through alternative pathways. Analyses among statin-naïve participants were not meaningfully different. Conclusions: Mendelian randomization estimates did not achieve statistical significance, but the direction of associations suggests that polyps are more prevalent among those with inherited susceptibility to increased LDL and TG. Results also highlight difficulties interpreting results from Mendelian randomization analyses of traits with complex biology, given that variants may be pleiotropic and not suitable for use as instrumental variables. Citation Format: Michael N. Passarelli, Polly A. Newcomb, Karen W. Makar, Andrea N. Burnett-Hartman, John D. Potter, Melissa P. Upton, Lee-Ching Zhu, Michael E. Rosenfeld, Stephen M. Schwartz, Carolyn M. Rutter. Blood lipids, colorectal adenomas, and non-adenomatous polyps: A comparison of associations from clinical measurements and Mendelian randomization. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 294. doi:10.1158/1538-7445.AM2014-294

Impact of Organised Screening Program By Fecal Occult Blood Test on the Diagnosis Rate of Colorectal Adenomas: a Population-Based Study

ABSTRACT Aim: Pilot colorectal cancer screening programs using a biennial fecal occult blood test (FOBT) started in France in 2003. A population-based Registry of adenomas, covering one of the pilot areas, gave the opportunity to describe time trends in the rate of diagnosis of colorectal adenomas, before and after the beginning of the screening program. Methods: The study relies on the only Registry which has been collecting since 1976 data on all cases of colorectal adenomas diagnosed in a well-defined administrative area (Cote-d'Or, France). This population-based study included all residents aged 50–74 years, with a first adenoma diagnosed between 01/1997 and 12/2008 and compared “pre- screening period” (1997-2002) with “post-screening period” (2003-2008). Standardized diagnosis rates were calculated by 5-year age group, gender and calendar year. Annual percentage changes were estimated using a Poisson regression model. Results: Over the study period, 4,908 men and 3,133 women were first-diagnosed with colorectal adenoma. High-risk adenomas (>1cm, villous component and/or high grade dysplasia) were found in 38.7% of them. For high-risk adenomas, age-standardized diagnosis rates were 136/100,000 before screening program and 257/100,000 after, with a percentage change of 89%. The corresponding rates for non-advanced adenomas were respectively: 235 and 392/100,000, with a percentage change of 68%. Data obtained on participation and positivity of tests for included individuals allowed to examine results according to these parameters. Conclusions: In actual conditions of clinical practice, we showed a marked increase in the rate of first adenoma diagnosis after 3 biennial colorectal cancer screening rounds, especially for high-risk adenomas. These results reinforce the interest of extending organized mass screening program. Using immunochemical FOBT, which showed better performance than guaiac-FOBT, will also improve results in the future. Disclosure: All authors have declared no conflicts of interest.

Incidental colonic focal FDG uptake on PET/CT: can the maximum standardized uptake value (SUVmax) guide us in the timing of colonoscopy?

In patients undergoing (18)F-FDG PET/CT, incidental colonic focal lesions can be indicative of inflammatory, premalignant or malignant lesions. The maximum standardized uptake value (SUVmax) of these lesions, representing the FDG uptake intensity, might be helpful in differentiating malignant from benign lesions, and thereby be helpful in determining the urgency of colonoscopy. The aim of our study was to assess the incidence and underlying pathology of incidental PET-positive colonic lesions in a large cohort of patients, and to determine the usefulness of the SUVmax in differentiating benign from malignant pathology. The electronic records of all patients who underwent FDG PET/CT from January 2010 to March 2013 in our hospital were retrospectively reviewed. The main indications for PET/CT were: characterization of an indeterminate mass on radiological imaging, suspicion or staging of malignancy, and suspicion of inflammation. In patients with incidental focal FDG uptake in the large bowel, data regarding subsequent colonoscopy were retrieved, if performed within 120 days. The final diagnosis was defined using colonoscopy findings, combined with additional histopathological assessment of the lesion, if applicable. Of 7,318 patients analysed, 359 (5 %) had 404 foci of unexpected colonic FDG uptake. In 242 of these 404 lesions (60 %), colonoscopy follow-up data were available. Final diagnoses were: adenocarcinoma in 25 (10 %), adenoma in 90 (37 %), and benign in 127 (53 %). The median [IQR] SUVmax was significantly higher in adenocarcinoma (16.6 [12 - 20.8]) than in benign lesions (8.2 [5.9 - 10.1]; p < 0.0001), non-advanced adenoma (8.3 [6.1 - 10.5]; p < 0.0001) and advanced adenoma (9.7 [7.2 - 12.6]; p < 0.001). The receiver operating characteristic curve of SUVmax for malignant versus nonmalignant lesions had an area under the curve of 0.868 (SD ± 0.038), the optimal cut-off value being 11.4 (sensitivity 80 %, specificity 82 %, positive predictive value 34 %, negative predictive value 98 %). In these patients with incidental colonic focal activity undergoing PET/CT (the largest series published to date), malignancies had significantly higher SUVmax values than all other types of lesions. However, SUVmax could not distinguish between benign lesions and adenomas. In conclusion, all incidental findings in the colon should be further evaluated and lesions with SUVmax ≥11.4 should be evaluated without delay.

Adenomatous neoplasia: postsurgical incidence after normal preoperative CT colonography findings in the colon proximal to an occlusive cancer.

To determine the postoperative incidence of adenomatous neoplasia in the colon proximal to an occlusive colorectal cancer where preoperative computed tomographic (CT) colonography findings were normal. Institutional review board approval, with a waiver of informed consent, was obtained. This observational study included patients with occlusive colorectal cancer who underwent preoperative CT colonography between April 2007 and March 2010 that revealed normal findings (ie, no lesions ≥ 6 mm) in the proximal colon and who underwent postoperative colonoscopy. The primary outcome was postoperative colonoscopic discovery of clinically relevant lesions (ie, nondiminutive [≥ 6 mm] adenomas, advanced adenomas, or cancers) in the proximal colon. The cumulative incidence of clinically relevant lesions in preoperatively normal proximal colon over the postsurgical follow-up time was analyzed by using the Kaplan-Meier method. The final cohort included 204 patients (102 men and 102 women; mean age, 57.3 years ± 11.3 [standard deviation]). At a total of 435 postoperative colonoscopies performed over a median follow-up of 29 months (range, 1-74 months), clinically relevant lesions were detected in the proximal colon in 30 patients: Nonadvanced adenomas were detected in 23 patients, and advanced adenomas were detected in seven patients. The cumulative incidence of clinically relevant adenomatous lesions in the preoperatively normal proximal colon 12 and 18 months after preoperative CT colonography was 8.1% (95% confidence interval [CI]: 3.9%, 12.2%) and 9.6% (95% CI: 5%, 14%), respectively. Clinically relevant adenomatous lesions found in the proximal colon within 18 months of preoperative CT colonography were nonadvanced adenomas in 10 of 15 patients. When the portion of the colon proximal to an occlusive cancer is devoid of nondiminutive lesions at preoperative CT colonography, colonoscopy of the proximal colon following cancer resection rarely finds clinically relevant lesions and is unlikely to reveal any lesions requiring immediate removal until routine 1-year postsurgical follow-up. Online supplemental material is available for this article .

OC-044 Predictors Of Advanced Neoplasia At Surveillance In Screening Population- A Study Of All High And Intermediate Risk Gorup Subjects In First Six Year Of Nhs Bcsp

IntroductionIn NHS BCSP, high and intermediate risk subjects with colorectal adenomas undergo surveillance colonoscopies. This guideline evidence was derived mostly from general population based studies. This study aims to evaluate...