Serum matrix metalloproteinase 9 and colorectal neoplasia: a community-based evaluation of a potential diagnostic test.
ABSTRACT: A blood test may be a more acceptable routine colorectal cancer (CRC) screening test than faecal occult blood test, flexible sigmoidoscopy or colonoscopy, and could be safer and cheaper. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test for CRC in a non-presenting symptomatic population.A cohort, aged 50-69 with lower gastrointestinal symptoms, was identified by community-based survey. Accuracy of serum MMP9 was assessed by comparison with colonoscopy. Logistic regression identified predictors of neoplasia and receiver operating characteristic curve analyses determined the cutoff to maximise the sensitivity.Data were available for 748 patients. Overall, 46 cases of neoplasia were identified. Univariate analysis demonstrated that demographic characteristics, behavioural factors, clinical symptoms and raised serum MMP9 concentration were all significantly associated with the presence of neoplasia. Our final logistic regression model had a sensitivity of 79% and specificity of 70%.We demonstrated a significant association between serum MMP9 concentration and the presence of neoplasia. Serum MMP9 levels are raised in those with cancer and high-risk adenomas, although MMP9 estimation is likely to have the greatest predictive utility when used as part of a panel of biomarkers. Further work is required to identify biomarkers that are sufficiently accurate for implementing into routine practice.
Project description:The U.S. Preventive Services Task Force recommends against routine screening for colorectal cancer (CRC) in adequately screened persons older than 75 years but does not address the appropriateness of screening in elderly persons without previous screening.To determine at what ages CRC screening should be considered in unscreened elderly persons and to determine which test is indicated at each age.Microsimulation modeling study.Observational and experimental studies.Unscreened persons aged 76 to 90 years with no, moderate, and severe comorbid conditions.Lifetime.Societal.One-time colonoscopy, sigmoidoscopy, or fecal immunochemical test (FIT) screening.Quality-adjusted life-years gained, costs, and costs per quality-adjusted life-year gained.In unscreened elderly persons with no comorbid conditions, CRC screening was cost-effective up to age 86 years. Screening with colonoscopy was indicated up to age 83 years, sigmoidoscopy was indicated at age 84 years, and FIT was indicated at ages 85 and 86 years. In unscreened persons with moderate comorbid conditions, screening was cost-effective up to age 83 years (colonoscopy indicated up to age 80 years, sigmoidoscopy at age 81 years, and FIT at ages 82 and 83 years). In unscreened persons with severe comorbid conditions, screening was cost-effective up to age 80 years (colonoscopy indicated up to age 77 years, sigmoidoscopy at age 78 years, and FIT at ages 79 and 80 years).Results were most sensitive to assuming a lower willingness to pay per quality-adjusted life-year gained.Only persons at average risk for CRC were considered.In unscreened elderly persons CRC screening should be considered well beyond age 75 years. A colonoscopy is indicated at most ages.National Cancer Institute.
Project description:PURPOSE:Colonoscopy and flexible sigmoidoscopy are both recommended colorectal cancer (CRC) screening strategies, but their relative effectiveness is unclear. We sought to evaluate the ability of each of these two modalities to reduce CRC mortality. METHODS:We conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Cases were persons aged 70-85 years who died of CRC and were matched to up to three non-CRC controls. Receipt of endoscopy was ascertained from Medicare claims and endoscopy indication assigned using a validated algorithm. Conditional logistic regression models were developed to estimate the association between screening colonoscopy or sigmoidoscopy and CRC mortality. We conducted secondary analyses by race, sex, and endoscopist characteristics, and with varying duration of the look-back period. RESULTS:In the initial analysis using all available look-back years, screening flexible sigmoidoscopy was associated with a 35% reduction in CRC mortality (OR 0.65, 95% CI 0.48, 0.89), while screening colonoscopy was associated with a 74% reduction (OR 0.26, 95% CI 0.23, 0.30). Sigmoidoscopy was not associated with any reduction in proximal CRC mortality. The association between colonoscopy and reduced CRC mortality was stronger in the distal than the proximal colon. Results were similar in analyses using a 5-year look-back period. CONCLUSIONS:Screening colonoscopy was associated with greater reductions in CRC mortality than screening sigmoidoscopy, and with a greater reduction in the distal than the proximal colon. These results provide additional information on the relative benefits of screening for CRC with sigmoidoscopy and colonoscopy.
Project description:The Affordable Care Act (ACA) eliminated cost-sharing for evidence-based preventive services in an effort to encourage use.To evaluate use of colorectal cancer (CRC) screening in a national population-based sample before and after implementation of the ACA.Repeated cross-sectional analysis of the Medical Expenditure Panel Survey (MEPS) between 2009 and 2012 comparing CRC screening rates before and after implementation of the ACA.Adults 50-64 with private health insurance and adults 65-75 with Medicare.Self-reported receipt of screening colonoscopy, sigmoidoscopy, or fecal occult blood test (FOBT) within the past year among those eligible for screening.Our study included 8617 adults aged 50-64 and 3761 adults aged 65-75. MEPS response rates ranged from 58 to 63%. Among adults aged 50-64, 18.9-20.9% received a colonoscopy in the survey year, 0.59-2.1% received a sigmoidoscopy, and 7.9-10.4% received an FOBT. For adults aged 65-75, 23.6-27.7% received a colonoscopy, 1.3-3.2% a sigmoidoscopy, and 13.5-16.4% an FOBT. In adjusted analyses, among participants aged 50-64, there was no increase in yearly rates of colonoscopy (-0.28 percentage points, 95% CI -2.3 to 1.7, p?=?0.78), sigmoidoscopy (-1.1%, 95% CI -1.7 to -0.46, p?=?<0.001), or FOBT (-1.6%, 95% CI -3.2 to -0.03, p?=?0.046) post-ACA. For those aged 65-75, rates of colonoscopy (+2.3%, 95% CI -1.4 to 6.0, p?=?0.22), sigmoidoscopy (+0.34%, 95% CI 0.88 to 1.6, p?=?0.58) and FOBT (-0.65, 95% CI -4.1 to 2.8, p?=?0.72) did not increase. Among those aged 65-75 with Medicare and no additional insurance, the use of colonoscopy rose by 12.0% (95% CI 3.3 to 20.8, p?=?0.007). Among participants with Medicare living in poverty, colonoscopy use also increased (+5.7%, 95% CI 0.18 to 11.3, p?=?0.043).Eliminating cost-sharing for CRC screening has not resulted in changes in the use of CRC screening services for many Americans, although use may have increased in the post-ACA period among some Medicare beneficiaries.
Project description:BACKGROUND:Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors. METHODS:We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms. RESULTS:Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations. CONCLUSIONS:PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.
Project description:We previously described the over-expression of nucleoside diphosphate kinase A (NDKA) in tumours and serum from colorectal cancer (CRC) patients, suggesting its use as biomarker. In this study we evaluated the diagnostic accuracy of serum NDKA to detect advanced neoplasia (CRC or advanced adenomas). Furthermore, the performance of NDKA was compared with the faecal immunochemical test (FIT). The study population included a case-control cohort and a screening cohort (511 asymptomatic first-degree relatives of CRC patients that underwent a colonoscopy and a FIT). Serum NDKA was elevated in CRC patients in the case-control cohort (p?=?0.002). In the screening cohort, NDKA levels were higher for advanced adenomas (p?=?0.010) and advanced neoplasia (p?=?0.006) compared to no neoplasia. Moreover, elevated NDKA was associated with severe characteristics of adenomas (?3 lesions, size???1?cm or villous component). Setting specificity to 85%, NDKA showed a sensitivity of 30.19% and 29.82% for advanced adenomas and advanced neoplasia, respectively. NDKA combined with FIT (100?ng/mL cut-off) detected advanced adenomas and advanced neoplasia with 45.28% and 49.12% sensitivity, with specificity close to 90%. The combination of serum NDKA and FIT can improve the detection of advanced neoplasia, mainly for lesions located on the proximal colon, in asymptomatic individuals with CRC family-risk.
Project description:BACKGROUND:Quantitative faecal immunochemical tests measure faecal haemoglobin concentration (f-Hb), which increases in the presence of colorectal neoplasia. OBJECTIVE:We examined the diagnostic accuracy of faecal immunochemical test (FIT)in patients at increased risk of colorectal cancer (CRC) attending for surveillance colonoscopy as per national guidelines. METHODS:A total of 1103 consecutive patients were prospectively invited to complete a FIT before their scheduled colonoscopy in two university hospitals in 2014- 2016. F-Hb was analysed on an OC-Sensor io automated analyser (Eiken Chemical Co., Ltd, Tokyo, Japan) with a limit of detection of 2 µg Hb/g faeces. The diagnostic accuracy of f-Hb for CRC and higher-risk adenoma was examined. RESULTS:A total of 643 patients returned a faecal test. After excluding 4 patients with known inflammatory bowel disease, 639 (57.9%) remained in the study: age range: 25-90 years (median: 64 years, interquartile range (IQR): 55-71): 54.6% male. Of 593 patients who also completed colonoscopy, 41 (6.9%) had advanced neoplasia (4 CRC, 37 higher-risk adenoma). Of the 238 patients (40.1%) who had detectable f-Hb, 31 (13.0%) had advanced neoplasia (2 CRC, 29 higher-risk adenoma) compared with 10 (2.8%) in those with undetectable f-Hb (2 CRC, 8 higher-risk adenoma). Detectable f-Hb gave negative predictive values of 99.4% for CRC and 97.2% for CRC plus higher-risk adenoma. CONCLUSION:In patients at increased risk of CRC under colonoscopy surveillance, a test measuring faecal haemoglobin can provide an objective estimate of the risk of advanced neoplasia, and could enable tailored scheduling of colonoscopy.
Project description:Screening colonoscopy and flexible sigmoidoscopy (FSG) reduce the risk of colorectal cancer (CRC), but the magnitude and duration of protection, particularly against right-sided cancer, remain uncertain. We computed the incremental benefit of colonoscopy over FSG using a validated mathematical model, which reflects colorectal neoplasia growth characteristics while allowing uncertainty in endoscopic detection and removal of adenomas.We calibrated models of CRC incidence within a multistage clonal expansion framework to data from: (1) San Francisco-Oakland SEER registry (reference population) and (2) FSG long-term follow-up data from 50,757 individuals after a negative FSG in the Kaiser Permanente system. We compared the residual CRC risks after FSG with full-length colonoscopy.Our model mirrors trial data with 10-year CRC risk reductions after FSG screening at age 50 years of approximately one-third; the optimal age for a 'once-only' FSG exam was between ages 50 and 60 years; and the greater benefit was for men compared with women. There were considerable incremental gains in reduction in CRC risk by colonoscopy compared with FSG with the greatest benefit for screening colonoscopy at age 50 years. These results held up against lowering the right-sided adenoma detection sensitivity by 30%, as well as reducing the curative efficacy of polypectomy throughout the colon.Mathematical modeling of CRC screening, which takes account of important aspects of tumor biology, demonstrates superior risk reductions by colonoscopy over FSG. Our predictions provide further rationale for recommending screening colonoscopy in average-risk populations before the age of 60.
Project description:Colorectal cancer (CRC) screening is a cost-effective prevention and control strategy. However, the promotion of CRC screening for older adults may be difficult because reading CRC prevention information may evoke embarrassment, fear, and anxiety towards the screening procedure and cancer diagnosis. This study aims to (1) examine the effects of three promotional materials for CRC screening on the attitudes toward CRC screening tests (screening interest, screening effectiveness, and trust in the screening results) and cancer fear, and (2) to explore the interaction effect of cancer fear with screening effectiveness and trust in the screening results on screening interest of the three screening tests (fecal occult blood test (FOBT), flexible sigmoidoscopy, and colonoscopy) among Chinese older adults. A total of 114 community-dwelling older adults were asked to look at the corresponding promotional materials (pamphlet, cartoon, and video) of one of the three study groups. The pamphlet and video represent convention strategies and the cartoon represents an innovative strategy. No significant difference was observed in the screening interest and cancer fear across groups. FOBT was the most preferred screening modality. The video group has a large proportion agreed screening effectiveness of flexible sigmoidoscopy than pamphlet and cartoon groups and trusted in the screening results for FOBT and flexible sigmoidoscopy than the pamphlet group. Logistic regression results showed that the effect of trust in the screening results on screening interest for colonoscopy was greater among participants with higher cancer fear than those with lower cancer fear level. In conclusion, the three promotional groups had produced similar results in their attitudes toward CRC screening and cancer fear. The use of cartoons may be a comparable approach with conventional methods in the promotion of CRC screening. Additional components that can arouse fear and boost response efficacy simultaneously might also be useful for the effective promotion of colonoscopy among Chinese older adults.
Project description:<h4>Background</h4>Decision aids can improve decision making processes, but the amount and type of information that they should attempt to communicate is controversial. We sought to compare, in a pilot randomized trial, two colorectal cancer (CRC) screening decision aids that differed in the number of screening options presented.<h4>Methods</h4>Adults ages 48-75 not currently up to date with screening were recruited from the community and randomized to view one of two versions of our previously tested CRC screening decision aid. The first version included five screening options: fecal occult blood test (FOBT), sigmoidoscopy, a combination of FOBT and sigmoidoscopy, colonoscopy, and barium enema. The second discussed only the two most frequently selected screening options, FOBT and colonoscopy. Main outcomes were differences in screening interest and test preferences between groups after decision aid viewing. Patient test preference was elicited first without any associated out-of-pocket costs (OPC), and then with the following costs: FOBT-$10, sigmoidoscopy-$50, barium enema-$50, and colonoscopy-$200.<h4>Results</h4>62 adults participated: 25 viewed the 5-option decision aid, and 37 viewed the 2-option version. Mean age was 54 (range 48-72), 58% were women, 71% were White, 24% African-American; 58% had completed at least a 4-year college degree. Comparing participants that viewed the 5-option version with participants who viewed the 2-option version, there were no differences in screening interest after viewing (1.8 vs. 1.9, t-test p = 0.76). Those viewing the 2-option version were somewhat more likely to choose colonoscopy than those viewing the 5-option version when no out of pocket costs were assumed (68% vs. 46%, p = 0.11), but not when such costs were imposed (41% vs. 42%, p = 1.00).<h4>Conclusion</h4>The number of screening options available does not appear to have a large effect on interest in colorectal cancer screening. The effect of offering differing numbers of options may affect test choice when out-of-pocket costs are not considered.
Project description:The development of specific screening programs for individuals with a family history of colorectal cancer (CRC) is a priority. This study evaluates the diagnostic performance of serum soluble CD26 (sCD26) in family-risk individuals and compares this marker with the faecal immunochemical test for the detection of advanced neoplasia (AN) (CRC or advanced adenomas; AA).Five hundred and sixteen asymptomatic individuals with at least one first-degree relative with CRC were included. Serum sCD26 was measured in all the individuals who also underwent a colonoscopy (53 AA and four cancer cases were found) and a faecal immunochemical test.Setting specificity to 90% and 95%, respectively, sCD26 showed a sensitivity of 39.6% and 28.3% for AA, and of 42.1% and 28.1% for AN. The combination of sCD26 and the faecal test detected AA and AN with a 52.8% and 56.1% sensitivity, corresponding to 93.5% specificity.The combination of serum sCD26 and the faecal blood test could result a valuable strategy for detecting AN in familial-risk CRC screening.