A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy.
ABSTRACT: OBJECTIVE: This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. DESIGN: We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. RESULTS: Advanced colorectal neoplasia was detected in 2544 of the 35,918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7-8. CONCLUSIONS: Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies.
Project description:BACKGROUND:Fast-track colonoscopy to detect patients with colorectal cancer based on high-risk symptoms is associated with low sensitivity and specificity. The aim was to derive a predictive score of advanced colonic neoplasia in symptomatic patients in fast-track programs. METHODS:All patients referred for fast-track colonoscopy were evaluated. Faecal immunological haemoglobin test (3 samples; positive> 4 μg Hb/g), and a survey to register clinical variables of interest were performed. Colorectal cancer and advanced adenoma were considered as advanced colonic neoplasia. A sample size of 600 and 500 individuals were calculated for each phase 1 and phase 2 of the study, respectively (Phase 1, derivation and Phase 2, validation cohort). A Bayesian logistic regression analysis was used to derive a predictive score. RESULTS:1495 patients were included. Age (OR, 21), maximum faecal-Hb value (OR, 2.3), and number of positive samples (OR, 28) presented the highest ORs predictive of advanced colonic neoplasia. The additional significant predictive variables adjusted for age and faecal-Hb variables in Phase 1 were previous colonoscopy (last 5 years) and smoking (no, ex/active). With these variables a predictive score of advanced colonic neoplasia was derived. Applied to Phase 2, patients with a Score > 20 had an advanced colonic neoplasia probability of 66% (colorectal cancer, 32%), while those with a Score ≤ 10, a probability of 10% (colorectal cancer, 1%). Prioritizing patients with Score > 10, 49.4% of patients would be referred for fast-track colonoscopy, diagnosing 98.3% of colorectal cancers and 77% of advanced adenomas. CONCLUSIONS:A scoring system was derived and validated to prioritize fast-track colonoscopies according to risk, which was efficient, simple, and robust.
Project description:BACKGROUND:Several methods are recommended equally strongly for colorectal cancer screening in average-risk persons. Risk stratification would enable tailoring of screening within this group, with less invasive tests (sigmoidoscopy or occult blood tests) for lower-risk persons and colonoscopy for higher-risk persons. OBJECTIVE:To create a risk index for advanced neoplasia (colorectal cancer and adenomas or serrated polyps ?1.0 cm, villous histology, or high-grade dysplasia) anywhere in the colorectum, using the most common risk factors for colorectal neoplasia. DESIGN:Cross-sectional study. SETTING:Multiple endoscopy units, primarily in the Midwest. PATIENTS:Persons aged 50 to 80 years undergoing initial screening colonoscopy (December 2004 to September 2011). MEASUREMENTS:Derivation and validation of a risk index based on points from regression coefficients for age, sex, waist circumference, cigarette smoking, and family history of colorectal cancer. RESULTS:Among 2993 persons in the derivation set, prevalence of advanced neoplasia was 9.4%. Risks for advanced neoplasia in persons at very low, low, intermediate, and high risk were 1.92% (95% CI, 0.63% to 4.43%), 4.88% (CI, 3.79% to 6.18%), 9.93% (CI, 8.09% to 12.0%), and 24.9% (CI, 21.1% to 29.1%), respectively (P < 0.001). Sigmoidoscopy to the descending colon in the low-risk groups would have detected 51 of 70 (73% [CI, 61% to 83%]) advanced neoplasms. Among 1467 persons in the validation set, corresponding risks for advanced neoplasia were 1.65% (CI, 0.20% to 5.84%), 3.31% (CI, 2.08% to 4.97%), 10.9% (CI, 8.26% to 14.1%), and 22.3% (CI, 16.9% to 28.5%), respectively (P < 0.001). Sigmoidoscopy would have detected 21 of 24 (87.5% [CI, 68% to 97%]) advanced neoplasms. LIMITATIONS:Split-sample validation; results apply to first-time screening. CONCLUSION:This index stratifies risk for advanced neoplasia among average-risk persons by identifying lower-risk groups for which noncolonoscopy strategies may be effective and efficient and a higher-risk group for which colonoscopy may be preferred. PRIMARY FUNDING SOURCE:National Cancer Institute, Walther Cancer Institute, Indiana University Simon Cancer Center, and Indiana Clinical and Translational Sciences Institute.
Project description:Identification of single-nucleotide polymorphisms (SNP) associated with development of advanced colorectal adenomas.Discovery phase: 1,406 Caucasian patients (139 advanced adenoma cases and 1,267 controls) from the Adenoma Prevention with Celecoxib (APC) trial were included in a genome-wide association study (GWAS) to identify variants associated with postpolypectomy disease recurrence. Genome-wide significance was defined as false discovery rate less than 0.05, unadjusted P = 7.4 × 10(-7). Validation phase: results were further evaluated using 4,175 familial colorectal adenoma cases and 5,036 controls from patients of European ancestry [COloRectal Gene Identification consortium (CORGI), Scotland, Australia, and VQ58].Our study identified eight SNPs associated with advanced-adenoma risk in the APC trial (rs2837156, rs7278863, rs2837237, rs2837241, rs2837254, rs741864 at 21q22.2, and rs1381392 and rs17651822 at 3p24.1, at P < 10(-7) level with OR > 2). Five variants in strong pairwise linkage disequilibrium (rs7278863, rs2837237, rs741864, rs741864, and rs2837241; r(2) = 0.8-1) are in or near the coding region for the tight junction adhesion protein, IGSF5. An additional variant associated with advanced adenomas, rs1535989 [minor allele frequency, 0.11; OR, 2.09; 95% confidence interval (CI), 1.50-2.91], also predicted colorectal cancer development in a validation analysis (P = 0.019) using a series of adenoma cases or colorectal cancer (CORGI study) and 3 sets of colorectal cancer cases and controls (Scotland, VQ58, and Australia; N = 9,211).Our results suggest that common polymorphisms contribute to the risk of developing advanced adenomas and might also contribute to the risk of developing colorectal cancer. The variant at rs1535989 may identify patients whose risk for neoplasia warrants increased colonoscopic surveillance.
Project description:Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms.A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR.Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (?5 mm) than in healthy subjects.Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia.
Project description: To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis. Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries. Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events. Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria. 15 randomized controlled trials (12?234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous colorectal cancer could not be estimated. Among individuals with previous colorectal neoplasia, non-aspirin NSAIDs are the most effective agents for the prevention of advanced metachronous neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile. PROSPERO (CRD42015029598).
Project description:BACKGROUND:Colon capsule endoscopy (CCE) and CT colonography (CTC) are minimally invasive techniques for colorectal cancer (CRC) screening. Our objective is to compare CCE and CTC for the identification of patients with colorectal neoplasia among participants in a CRC screening programme with positive faecal immunochemical test (FIT). Primary outcome was to compare the performance of CCE and CTC in detecting patients with neoplastic lesions. METHODS:The VICOCA study is a prospective, single-centre, randomised trial conducted from March 2014 to May 2016; 662 individuals were invited and 349 were randomised to CCE or CTC before colonoscopy. Endoscopists were blinded to the results of CCE and CTC. RESULTS:Three hundred forty-nine individuals were included: 173 in the CCE group and 176 in the CTC group. Two hundred ninety individuals agreed to participate: 147 in the CCE group and 143 in the CTC group. In the intention-to-screen analysis, sensitivity, specificity and positive and negative predictive values for the identification of individuals with colorectal neoplasia were 98.1%, 76.6%, 93.7% and 92.0% in the CCE group and 64.9%, 95.7%, 96.8% and 57.7% in the CTC group. In terms of detecting significant neoplastic lesions, the sensitivity of CCE and CTC was 96.1% and 79.3%, respectively. Detection rate for advanced colorectal neoplasm was higher in the CCE group than in the CTC group (100% and 93.1%, respectively; RR?=?1.07; p?=?0.08). Both CCE and CTC identified all patients with cancer. CCE detected more patients with any lesion than CTC (98.6% and 81.0%, respectively; RR?=?1.22; p?=?0.002). CONCLUSION:Although both techniques seem to be similar in detecting patients with advanced colorectal neoplasms, CCE is more sensitive for the detection of any neoplastic lesion. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02081742 . Registered: September 16, 2013.
Project description:Patients with inflammatory bowel disease (IBD) colitis are at an increased risk of developing colorectal cancer and are currently recommended to undergo extensive annual or biennial colonoscopy, a costly and invasive procedure. Most surveillance colonoscopies are negative with no existing objective measures for assessing their risk of developing cancer. We have recently developed a less invasive, cost-effective and objective method to assess cancer risk by detecting the presence of colonic neoplasia via 3-dimensional (3D) nanoscale nuclear architecture mapping (nanoNAM) of normal-appearing rectal biopsies. To establish its translational relevance, we prospectively recruited 103 patients with IBD colitis undergoing surveillance colonoscopy and measured submicroscopic alterations in aberrant intrinsic nuclear architecture of epithelial cells from normal-appearing rectal biopsies with nanoNAM. The results were correlated with the histologic diagnoses from all random biopsies obtained during initial and follow-up colonoscopy within 3 years. Using nanoNAM-based structural characterization as input features into a soft margin-based ?-SVM risk classifier, we show that nanoNAM detects colonic neoplasia with AUC of 0.87 ± 0.04, sensitivity of 0.81 ± 0.09, and specificity of 0.82 ± 0.07 in the independent validation set. In addition, projecting nanoNAM features onto a 2-sphere reveals patients with low-risk and high-risk IBD colitis existing on separate hemispheres. Finally, we show that this ability to assess cancer risk translates to clinically-relevant estimation of individual-patient likelihood of being truly at risk. We demonstrate the potential of nanoNAM to identify patients with IBD at higher risk of developing cancer from normal-appearing rectum tissue, which may aid clinicians in patients with personalized IBD colitis surveillance.
Project description:BACKGROUND/AIMS:Diverticulosis and colorectal neoplasia share epidemiological trends and risk factors which are common in Western countries and incidences increase with age. However, the data on an association between diverticulosis and colorectal neoplasia are conflicting. Thus, we performed a meta-analysis to evaluate whether diverticulosis is associated with colorectal neoplasia. METHODS:A systematic literature search of PubMed, EMBASE, Cochrane Library, Web of Science, and SCOPUS was conducted to identify studies that investigated the association between diverticulosis and advanced colorectal neoplasia (advanced adenoma, colorectal cancer), adenomas, or polyps. The demographic characteristics of patients, including age, gender, indication for colonoscopy, confounding factors, and outcomes of colorectal neoplasia were assessed. RESULTS:We identified 29 cross-sectional studies (N = 450,953) that investigated the association between diverticulosis and colorectal neoplasia. The meta-analysis found that diverticulosis was not associated with advanced colorectal neoplasia (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.63-1.50). Although there was a positive correlation between diverticulosis and adenomas (OR 1.47, 95% CI 1.18-1.84) and diverticulosis and polyps (OR 1.95, 95% CI 1.15-3.31), diverticulosis did not increase the risk of adenomas (OR 1.34, 95% CI 0.87-2.06) in patients who underwent screening colonoscopy. Moreover, all the increased risk of colorectal neoplasia in patients with diverticulosis was observed in published studies only, and not in unpublished ones. CONCLUSIONS:This meta-analysis demonstrated that diverticulosis is not associated with an increased risk of advanced colorectal neoplasia. Although diverticulosis was associated with a higher risk of polyps and adenomas, the risk was not increased in screening populations. Moreover, the increased risk of colorectal neoplasia in patients with diverticulosis was observed only in published studies and not in unpublished ones.
Project description:BACKGROUND: There is increasing evidence that aspirin, statins and ACE-inhibitors can reduce the incidence of colorectal cancer. The aim of the present study was to assess the impact of these medications on an individual's risk of advanced neoplasia in a colorectal cancer screening programme. METHODS: A prospectively maintained database of the first round of screening in our geographical area was analysed. The outcome measure was advanced neoplasia (cancer or intermediate or high risk adenomata). RESULTS: Of the 4188 individuals who underwent colonoscopy following a positive occult blood stool test, colorectal pathology was present in 3043(73%). Of the 3043 patients with colorectal pathology, 1704(56%) had advanced neoplasia. Patients with advanced neoplasia were more likely to be older (OR 1.38; 95% CI 1.19-1.59) and male (OR 1.66; 95% CI 1.43-1.94) (both P<0.001). In contrast, those on aspirin (OR 0.68; 95% CI 0.56-0.83), statins (OR 0.65; 95% CI 0.55-0.78) or ACE inhibitors (OR 0.71; 95% CI 0.57-0.89) were less likely to have advanced neoplasia at colonoscopy (all P<0.05). CONCLUSION: In patients undergoing colonoscopy following a positive occult blood stool test with documented evidence of aspirin, statin or ACE-inhibitor usage, advanced neoplasia is less likely, suggesting that the usage of these medications may have a chemopreventative effect.
Project description:OBJECTIVES:Annual testing using either a high-sensitivity guaiac fecal occult blood test (HS-gFOBT) or a fecal immunochemical test (FIT) is recommended for screening average-risk people for colorectal cancer. We compared the performance characteristics of the HS-gFOBT Hemoccult II SENSA and two FITs (InSure FIT and OC FIT-CHEK) for detecting advanced colorectal neoplasia. METHODS:The study included 1,006 asymptomatic patients, aged 50-75 years, who were scheduled to receive a screening colonoscopy at gastroenterology practices in the Minneapolis and Indianapolis metropolitan areas. Each participant was asked to complete all three stool tests before their colonoscopy. Each test's performance characteristics were evaluated using the screening colonoscopic results as the reference standard. RESULTS:Sensitivity for detecting advanced colorectal neoplasia was highest for InSure FIT (26.3%, 95% confidence interval (CI) 15.9-40.7), followed by OC FIT-CHEK (15.1%, 95% CI 6.7-26.1) and Hemoccult II SENSA (7.4%, 95% CI 1.9-17.0). InSure FIT was statistically significantly more sensitive than both OC FIT-CHEK (absolute difference in sensitivity=11.2%, 95% CI 0.4-24.2) and Hemoccult II SENSA (difference in sensitivity=18.9%, 95% CI 10.2-32.6). Specificities were relatively high for all tests (between 96.8% and 98.6%). CONCLUSIONS:Our results suggest that some FITs are more sensitive than the HS-gFOBT Hemoccult II SENSA, but these results need to be confirmed in larger asymptomatic populations. Comparisons between the FITs examined in this study and other FITs are needed to determine the best tests for population screening.