Diagnostic accuracy of risk assessment and fecal immunochemical test in colorectal cancer screening: Results from a population-based program and meta-analysis.

BACKGROUND: Fecal immunochemical test (FIT) is a commonly used initial test for colorectal cancer (CRC) screening. Parallel use of FIT with risk assessment (RA) could improve the detection of non-bleeding lesions, but at the expense of compromising sensitivity. In this study, we evaluated the accuracy of FIT and/or RA in the Shanghai CRC screening program, and systematically reviewed the relevant evaluations worldwide. METHODS: RA and 2-specimen FIT were used in parallel in the Shanghai screening program, followed by a colonoscopy among those with positive results. Sensitivity, specificity, detection rate of CRC, positive predictive value (PPV), and other measures with their 95% confident intervals were calculated for each type of tests and several assumed combined tests. We further searched PubMed, Embase, Web of Science, and Cochrane Library for relevant studies published in English up to January 5, 2022. RESULTS: By the end of 2019, a total of 1,901,360 participants of the screening program completed 3,045,108 tests, with 1,901,360 first-time tests and 1,143,748 subsequent tests. Parallel use of RA and 2-specimen FIT achieved a sensitivity of 0.78 (0.77-0.80), a specificity of 0.78 (0.78-0.78), PPV of 0.89% (0.86-0.92), and a detection rate of 1.99 (1.93-2.05) for CRC per 1000 among participants enrolled in the first screening round, and performed similarly among those who participated for several times. A meta-analysis of 103 published observational studies demonstrated a higher sensitivity [0.76 (0.36, 0.94)] but a much lower specificity [0.59 (0.28, 0.85)] of parallel use of RA and FIT for detecting CRC in average-risk populations than in our subjects. One-specimen FIT, the most commonly used initial test, had a pooled specificity comparable to the Shanghai screening program (0.92 vs. 0.91), but a much higher pooled sensitivity (0.76 vs. 0.57). CONCLUSION: Our results indicate the limitation of FIT only as an initial screening test for CRC in Chinese populations, and highlight the higher sensitivity of parallel use of RA and FIT. Attempts should be made to optimize RA to improve effectiveness of screening in the populations.

Cost-effectiveness analysis of a community-based colorectal cancer screening program in Shanghai, China.

Background: Since 2011, through the Community-Based Colorectal Cancer Screening Program in Shanghai, China (SHcsp), residents aged >50 years were offered initial colorectal cancer screening using the fecal immunochemical test (FIT) and risk assessment questionnaire (RAQ) for free. Colonoscopy was then recommended for positive results. Objective: To evaluate the cost-effectiveness of the Community-Based Colorectal Cancer Screening Program in Shanghai, China from the payer perspective. Methods: This analysis estimated the long-term cost and effectiveness of the 2014-2016 SHcsp based on real-world follow-up data from the SHcsp database, Shanghai Cancer Registry System, vital statistics from Shanghai Municipal Center for Disease Control and Prevention and inpatient CRC expense data from hospitals. A decision-tree model and Markov model were constructed to simulate the 25-year health outcomes. The screening branch was the cohort with a definite diagnosis of adenoma, advanced adenoma, and CRC. The other branch was residents who were neither screened nor treated until CRC symptoms appeared. A payer prospective was adopted to measure direct costs and effectiveness by life years (LYs) and quality-adjusted life years (QALYs) gained, and were discounted by 3%. Stimulation robustness was tested by one-way sensitivity analysis. Results: Of 1,097,656 residents, 13,250 were diagnosed with adenoma, advanced adenoma, or CRC. Assuming those had not been found through screening, SHcsp resulted in 1,570.1 LYs and 13,984.3 QALYs gained at an extra cost of USD9.96 million. The incremental cost-effectiveness ratio (ICER) was USD6,342.02 per LY and USD712.08 per QALY obtained, far below the threshold of USD59,598 of three-time GDP per capita in Shanghai. Conclusion: The SHcsp was cost-effective than no screening strategy. The results were generalisable to the Chinese population for mass CRC screening.

Leaching behavior and environmental risk assessment of toxic metals in municipal solid waste incineration fly ash exposed to mature landfill leachate environment.

Solidification/stabilization pretreatment + landfill disposal in municipal solid waste (MSW) landfill sites is a widely accepted MSW incineration (MSWI) fly ash (FA) management strategy in China. However, in reality, the stability of FA disposed in MSW landfill sites may be affected by the organic landfill leachate environment. The purpose of this study was to explore the mobility and environmental risks of six toxic metals (Mn+, Pb/Zn/Cu/Cd/Cr/Ni), from raw and solidified/stabilized FA, by simulating a leaching environment with mature landfill leachate (MLL). The leaching of Mn+ mainly occurred in the early leaching stage, and their leaching behavior was controlled by the diffusion of surface Mn+ in the FA matrix. The destructive effect of dissolved organic matter (DOM) on the local precipitation-dissolution equilibrium of FA-leachate interface, the formation of non-adsorptive DOM-Mn+ complex (easy to migrate), and the competitive effect of DOM on the binding sites of Mn+ on the surface of the FA matrix may play an important role in increasing the leaching level of most Mn+. By contrast, the potential of solidified FA in reducing the environmental risk level of leached Mn+ was better than that of stabilized FA. However, the immobilization capability of solidification/stabilization pretreatment on various types of Mn+ in FA should be judged according to their practical disposal environment. Compared to MLL leaching tests, Acetic Acid Buffer Solution Method (HJ/T300-2007) can effectively strengthen the exposure environment and provide a reliable reference level of environmental risk for MSWI FA disposed in MSW landfill sites.

Genetic and clinical predictors for breast cancer risk assessment and stratification among Chinese women.

BACKGROUND: Most of the genetic variants identified from genome-wide association studies of breast cancer have not been validated in Asian women. No risk assessment model that incorporates both genetic and clinical predictors is currently available to predict breast cancer risk in this population. METHODS: We analyzed 12 single-nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies mostly of women of European ancestry as being associated with the risk of breast cancer in 3039 case patients and 3082 control subjects who participated in the Shanghai Breast Cancer Study. All participants were interviewed in person to obtain information regarding known and suspected risk factors for breast cancer. The c statistic, a measure of discrimination ability with a value ranging from 0.5 (random classification) to 1.0 (perfect classification), was estimated to evaluate the contribution of genetic and established clinical predictors of breast cancer to a newly established risk assessment model for Chinese women. Clinical predictors included in the model were age at menarche, age at first live birth, waist-to-hip ratio, family history of breast cancer, and a previous diagnosis of benign breast disease. The utility of the models in risk stratification was evaluated by estimating the proportion of breast cancer patients in the general population that could be accounted for above a given risk threshold as predicted by the models. All statistical tests were two-sided. RESULTS: Eight SNPs (rs2046210, rs1219648, rs3817198, rs8051542, rs3803662, rs889312, rs10941679, and rs13281615), each of which reflected a genetically independent locus, were found to be associated with the risk of breast cancer. A dose-response association was observed between the risk of breast cancer and the genetic risk score, which is an aggregate measure of the effect of these eight SNPs (odds ratio for women in the highest quintile of genetic risk score vs those in the lowest = 1.85, 95% confidence interval = 1.58 to 2.18, P(trend) = 2.5 x 10(-15)). The genetic risk score, the waist-to-hip ratio, and a previous diagnosis of benign breast disease were the top three predictors of the risk of breast cancer, each contributing statistically significantly (P < .001) to the full risk assessment model. The model, with a c statistic of 0.6295 after adjustment for overfitting, showed promise for stratifying women into different risk groups; women in the top 30% risk group accounted for nearly 50% of the breast cancers diagnosed in the general population. CONCLUSION: A risk assessment model that includes both genetic markers and clinical predictors may be useful to classify Asian women into relevant risk groups for cost-efficient screening and other prevention programs.