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Background and Aims Approximately 20-30% of colorectal cancers (CRC) arise from the serrated polyp pathway. CRC screening options have differential sensitivity to detect sessile serrated polyps (SSPs). We used the CRC-AIM model to assess how the detection of SSPs impacts predicted life-years gained (LYG), CRC incidence, and CRC mortality with multitarget stool DNA (mt-sDNA) or fecal immunochemical test (FIT) screening. Methods A simulated cohort of average-risk US individuals underwent triennial mt-sDNA or annual FIT screening between ages 45-75 years. SSP-attributed CRCs were modeled at 0% (base-case), 14.3%, 20%, and 30%, in combination with 4 adherence/attendance scenarios. S1: 100% stool-screening adherence/100% follow-up colonoscopy attendance after a positive stool-test. S2: reported stool-screening adherence (mt-sDNA=71%; FIT=43%)/100% follow-up colonoscopy attendance. S3: reported stool-screening adherence/reported follow-up colonoscopy attendance (mt-sDNA=72%; FIT=47%). S4: reported stool-screening adherence/72% follow-up colonoscopy attendance. Outcomes were per 1000 individuals. Sensitivity analyses used ranges of stool-screening adherence or follow-up attendance. Results At S1, S2, S3, and S4, LYG with FIT at base-case (0% SSP-attributed CRC) was 346.7, 279.3, 126.6, and 196.1, respectively, and with mt-sDNA was 324.6, 311.8, 215.8, and 215.8. Among the 4 adherence/attendance scenarios, modeling SSP-attributed CRCs decreased LYG by 4.9-20.9 with FIT and 2.0-5.1 with mt-sDNA. At S3 and 30% SSP-attributable CRCs, mt-sDNA had 95.1 more LYG, 21.5% greater CRC incidence reduction, and 22.2% greater CRC mortality reduction than FIT. Conclusions Incorporating SSPs and real-world adherence into the CRC-AIM modeling analyses yielded more practice-relevant estimates of CRC screening outcomes and should be applied in future studies to afford more appropriate assessment of comparative effectiveness estimates between guideline-endorsed screening options.

Purpose Colorectal cancer (CRC) is the second most deadly cancer in the USA. Early detection can improve CRC outcomes, but recent national screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test. We evaluated cross-sectional mt-sDNA test completion in a population of commercially and Medicare-insured patients. Methods Participants included individuals ages 50 years and older with commercial insurance or Medicare, with a valid mt-sDNA test shipped by Exact Sciences Laboratories LLC between January 1, 2018, and December 31, 2018 (n = 1,420,460). In 2020, we analyzed cross-sectional adherence, as the percent of successfully completed tests within 365 days of shipment date. Results Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance. Adherence increased with age: 60.8% for ages 50–64, 71.3% for ages 65–75, and 74.7% for ages 76 + years. Participants with mt-sDNA tests ordered by gastroenterologists had a higher adherence rate (78.3%) than those with orders by primary care clinicians (67.2%). Geographically, adherence rates were highest among highly rural patients (70.8%) and ordering providers in the Pacific region (71.4%). Conclusions Data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test, supporting its role as an accepted, noninvasive option for average-risk CRC screening. Attributes of mt-sDNA screening, including home-based convenience and accompanying navigation support, likely contributed to high completion rates.

BACKGROUND The US Preventive Services Task Force (USPSTF) includes multitarget stool DNA (mt-sDNA) testing as a colorectal cancer (CRC) screening option in average-risk individuals, but data on colonoscopy outcomes after positive mt-sDNA tests in community settings are needed. AIM The aim of this study was to investigate colonoscopy outcomes and quality following positive mt-sDNA in the population-based New Hampshire Colonoscopy Registry. METHODS We compared colonoscopy outcomes and quality between age-matched, sex-matched, and risk-matched patients from 30 endoscopy practices with and without a preceding positive mt-sDNA test. Main outcomes were colonoscopy findings of CRC, advanced noncancerous neoplasia, nonadvanced neoplasia, or normal examination. Quality measures included withdrawal time, bowel preparation quality, examination completion, and percentage of average-risk individuals with normal colonoscopies receiving a USPSTF-recommended 10 year rescreening interval. RESULTS Individuals with positive mt-sDNA tests (N=306, average age 67.0 y; 61.8% female) were significantly more likely than colonoscopy-only patients (N=918, 66.2 y; 61.8% female) to have CRC (1.3% vs. 0.4%) or advanced noncancerous neoplasia (27.1% vs. 8.2%) (P

Colorectal cancer is one of the most common cancers in the world. It is the second most common cause of cancer deaths in both genders in Poland. Screening tests allow for early cancer detection, resulting in reduced mortality and better prognosis. Tests include a stool test for occult blood, checking for biomarkers in faeces, and stool DNA testing. Colonoscopy remains the gold standard in the diagnosis of cancer, both in Poland and around the world. To convince patients of the importance of such testing, it is necessary to have a wider knowledge of all the available diagnostic tests, to understand their advantages and disadvantages. This article will give descriptions of the respective tests and compare their effectiveness in the diagnosis of colorectal cancer.

After 2 screen-setting studies showing high sensitivity for colorectal cancer and advanced precancerous lesions, multitarget stool DNA testing was endorsed by the US Preventative Services Task Force as a first-line colorectal cancer screening test. Uptake has increased exponentially since approval by the US Food and Drug Administration and Centers for Medicare and Medicaid Services. Adherence to testing is approximately 70%. Patients with positive results have high diagnostic colonoscopy completion rates in single-center studies. The positive predictive value for colorectal neoplasia in postapproval studies is high. Next-generation test prototypes show promise to extend specificity gains while maintaining high sensitivity.

Patient screening is important for early diagnosis of colorectal cancer (CRC). The present study aimed to compare the multitarget stool DNA (mt-sDNA) test with the fecal occult blood test (FOBT) for CRC screening. A total of 151 individuals were screened using colonoscopy, mt-sDNA and FOBT for the detection of CRC and adenoma. The results of the mt-sDNA test and FOBT were compared with colonoscopy to examine their sensitivity and specificity. Subsequently, the sensitivity and specificity of the mt-sDNA test were compared with those of FOBT in CRC and large adenoma. Stool samples were collected from patients with CRC (n=50) or large adenoma (n=51), as well as from normal controls (n=50). The mt-sDNA test outperformed FOBT in detecting CRC with a sensitivity of 90.0% (45/50) vs. 42.0% (21/50), advanced adenoma with a sensitivity of 70.6% (36/51) vs. 19.6% (10/51), stage I-III CRC with a sensitivity of 91.9% (34/37) vs. 29.7% (11/37), and stage IV CRC with a sensitivity of 84.6% (11/13) vs. 76.9% (10/13). In addition, the mt-sDNA test exhibited a specificity of 94.0% (47/50) in detecting CRC, which was superior to FOBT with a specificity of 90.0% (45/50). Therefore, the mt-sDNA test may have higher sensitivity and specificity compared with FOBT in diagnosing both CRC and advanced adenoma.

The most crucial step in molecular microbiology studies is choosing an appropriate procedure to obtain sufficient, high-quality DNA. Two commercially available kits (QIAamp DNA Stool Mini Kit and PSP Spin Stool DNA Plus Kit) and a modified in-house phenol-chloroform extraction method was compared for their efficiency in isolation of certain bacteria from human stool samples for Real-Time qPCR. DNA yield was significantly higher in Invitrogen when compared to phenol-chloroform method. Spiking experiments and qPCR results revealed that efficiency was in phenol-chloroform extraction was lower when compared to other two commercial kits. Commercial kits have better results in terms of DNA recovery and purity, and have more accurate results for qPCR experiments.

Background/Aim: Gut microbiota plays an important role in colorectal cancer (CRC) and its composition in CRC patients can be influenced by ethnicity and tumour genomics. Herein, the aim was to study the possible associations of ethnicity and gene mutations with the gut microbiota in CRC patients. Materials and Methods: Bacterial composition in stool samples of 83 CRC patients and 60 controls from Iran and Finland was studied by 16S rRNA gene sequencing. The association of gut microbiota composition with CRC, host mutations in KRAS, NRAS and TP53, and ethnicity analysed. Results: Beta diversity analysis indicated significant differences between the Iranian and Finnish gut microbiota composition, in both controls and patients' groups. The Iranian controls had higher abundance of Prevotella and lower abundance of Bacteroides compared to the Finnish controls, while the Finnish patients had higher abundance of Clostridium compared to Iranian patients. Abundance of Ruminococcus was higher in patients compared to the controls. Higher abundances of Herbaspirillum, Catenibacterium and lower abundances of Barnesiella were associated with mutations in NRAS, TP53, and RAS respectively. Conclusion: A possible link of host gene mutations with gut bacterial composition is suggested.

OBJECTIVES: Multitarget stool DNA (MT-sDNA) testing has grown as a noninvasive screening modality for colorectal cancer (CRC), but real-world clinical data are limited in the post-FDA approval setting. The effect of previous colonoscopy on MT-sDNA performance is not known. We aimed to evaluate findings of colorectal neoplasia (CRN) at diagnostic colonoscopy in patients with positive MT-sDNA testing, stratified by patient exposure to previous colonoscopy. METHODS: We identified consecutive patients completing MT-sDNA testing over a 39-month period and reviewed the records of those with positive tests for neoplastic findings at diagnostic colonoscopy. MT-sDNA test positivity rate, adherence to diagnostic colonoscopy, and the positive predictive value (PPV) of MT-sDNA for any CRN and neoplastic subtypes were calculated. RESULTS: Of 16,469 MT-sDNA tests completed, testing returned positive in 2,326 (14.1%) patients. After exclusion of patients at increased risk for CRC, 1,801 patients remained, 1,558 (87%) of whom underwent diagnostic colonoscopy; 918 of 1,558 (59%) of these patients had undergone previous colonoscopy, whereas 640 (41%) had not. Any CRN was found in 1,046 of 1,558 patients (PPV = 67%). More neoplastic lesions were found in patients without previous colonoscopy (73%); however, the rates remained high among those who had undergone previous colonoscopy (63%, P < 0.0001). The large majority (79%) of patients had right-sided neoplasia. DISCUSSION: MT-sDNA has a high PPV for any CRN regardless of exposure to previous colonoscopy. Right-sided CRN was found at colonoscopy in most patients with positive MT-sDNA testing, representing a potential advantage over other currently available screening modalities for CRC.

Objective To determine cross-sectional adherence with the multi-target stool DNA test used for colorectal cancer screening in a large, fully insured Medicare population. Methods All patients aged 65–85 with a valid multi-target stool DNA test order from 1 September 2016 to 31 August 2017 identified from the Exact Sciences Laboratories (Madison, WI; sole-source national multi-target stool DNA test provider) database were evaluated for test adherence. Cross-sectional adherence, defined as multi-target stool DNA test completion within 365 days from order date, was analyzed overall and by time to adherence, as well as by available patient (age, sex, test order date, Medicare coverage type) and provider (specialty, year of first multi-target stool DNA test order, multi-target stool DNA test order frequency, and practice location) factors. Results Among 368,494 Medicare beneficiaries (64% female), overall cross-sectional adherence was 71%. Cumulative adherence rates increased more rapidly at 30 (44%) and 60 (65%) days, followed by more gradual increases at 90 (67%), 180 (70%), and 365 (71%) days. By provider specialty, primary care clinicians represented a higher percentage of multi-target stool DNA orders than gastroenterologists (88% vs. 6%), but had a lower associated patient adherence rate (71% vs. 78%). Conclusions In this large, national sample of Medicare insured older adults, nearly three-quarters of patients adhered with a multi-target stool DNA order for colorectal cancer screening. These real-world data should inform further clinical and population health applications, reimbursement model simulations, and guideline-endorsed colorectal cancer screening strategies adherence.

Purpose FIT-DNA test is supposed to be highly sensitive for advanced colorectal neoplasms and is advocated in some developed countries, but lack extensive use in developing countries. Methods A case control study on stool DNA test for colorectal neoplasms patients was conducted from March 2016 to October 2017 in China. We recruited CRC, colorectal neoplasms and normal controls from ambulatory patients and screening attendees in communities. The stool DNA was tested by a molecular panel similar as ColoGuard in addition to fecal immunochemical test(FIT) in a blinded manner. A risk scoring system was used to determine the positiveness of tests with histological diagnosis as its reference standard. Results Eligible subjects included 203 colorectal cancer (CRC), 49 advanced adenoma (AA), 156 non-advanced adenoma(NAA) and 431 normal controls(NC). The FIT-DNA kit detected 97.5% CRC (n = 198, 95% CI = 95.4–99.7) and 53.1% AA (n = 26, 95% CI = 39.1–67.0), with specificity of 89.1% (95% CI = 86.2–92.0) in NC and 88.1% (95% CI = 85.5–90.7) in non-advanced controls. The FIT embedded in the kit alone identified 94.6% (n = 192, 95% CI = 91.5–97.7) CRC and 36.7% AA (n = 18, 95% CI = 23.2–50.2). Consistency of KRAS mutation, BMP3 methylation, NDRG4 methylation in 26 paires stool DNA and CRC tumor DNA were 80.9%, 71.4% and 81.8%, respectively. Conclusion At the sacrifice of significantly decreased specificity, a FIT-DNA kit may has better sensitivity than FIT for predicting advanced colorectal adenoma, but not for predicting colorectal cancer. More evidences are needed for the extensive use of FIT-DNA testing.

Background: The serrated pathway for colorectal cancer (CRC) development is increasingly recognized. Patients with sessile serrated lesions (SSLs) that are large (≥10 mm) and/or have dysplasia (i.e., high-risk SSLs) are at higher risk of progression to CRC. Detection of SSLs is challenging given their predominantly flat and right-sided location. The yield of non-invasive screening tests for detection of high-risk SSLs is unclear. Objective: The aim of this study was to compare non-invasive screen detection of high-risk SSLs between the multi-target stool DNA test (mt-sDNA; Cologuard) and CT colonography (CTC). Methods: This retrospective study included 7974 asymptomatic adults (4705 women, 3269 men; mean age 60.0 years) who underwent CRC screening at a single center by mt-sDNA (Cologuard) from 2014-2019 (n=3987) or by CTC from 2009-2019 (n=3987). Clinical interpretations of CTC examinations were recorded. Subsequent colonoscopy findings and histology of resected polyps were also recorded. Chi-square or two-sample t tests were used to compare results between mt-sDNA and CTC using 6-mm and 10-mm thresholds for test positivity. Results: The overall colonoscopy referral rate for a positive screening test was 13.1% (522/3987) for mt-sDNA versus 12.2% (487/3987; p=.23) and 6.5% (260/3987; p

Colorectal cancer (CRC) rated among the three most diagnosed cancers and the fourth main cause of death worldwide. CRC is a curable cancer provided to be diagnosed at its early-stage. Colonoscopy, stool and blood-based tests are in use for CRC diagnosis/screening. Due to low patient compliance, low specificity and high rate of false results, more reliable methods with desired level of detection accuracy and high patients’ compliance are highly demanded. Detecting hotspot mutations in stool DNA emerged as a robust noninvasive alternative, but due to the different genetic background of various populations and hence varied mutation spectrum/prevalence, prior assessment of CRC mutations in the population is essential. Here, we have evaluated stool DNAs from CRC patients and controls using a NGS based 22 genes panel. Hotspot mutations in NRAS, FGFR3, SMAD4 and TP53 genes had higher prevalence among the CRC patients compare to normal controls. Patients were followed up in their post-surgical period. Six of them (12%) with TP53 mutations (2 patients had NRAS mutation as well) were died of cancer. Those harboring mutations in TP53 and/or NRAS would be regarded as high risk and should be provided with special care.

Purpose of Review Multi-target stool DNA (MT-sDNA) was approved in 2014 for use in screening average-risk patients for colorectal cancer (CRC). Here, we highlight recent literature from post-market studies to provide an update on clinical use and utility not possible from pre-approval studies. Recent Findings MT-sDNA has been included in major society guidelines as an option for colorectal cancer screening, and has seen exponentially increasing use in clinical practice. MT-sDNA appears to be attracting new patients to CRC screening, and patient adherence to diagnostic colonoscopy after a positive MT-sDNA test is high. Approximately two-thirds of these patients are found to have colorectal neoplasia (CRN), 80% of whom have at least one right-sided lesion; 1 in 3 will have advanced CRN. High yield of CRN is due not only to post-screening increase in probability but also likely improved endoscopist attention. In those with a negative high-quality colonoscopy after positive MT-sDNA test (“false positive MT-sDNA”), further interventions do not appear to be necessary. Summary MT-sDNA is a promising tool to improve rates and quality of CRC screening. Further investigation should examine MT-sDNA performance in populations at increased risk for CRC, and as an interval test after colonoscopy to detect potentially missed lesions.

Introduction Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose. Methods In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0-9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy. Results Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy. Discussion The high PPV of mt-sDNA 0-9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo. mt-sDNA as an interval test after negative screening colonoscopy warrants further study.

INTRODUCTION We evaluated the off-label use of multitarget stool DNA (mt-sDNA) testing in the primary care setting. METHODS We reviewed all mt-sDNA orders between July 1, 2018, and June 30, 2019, to determine the frequency of off-label mt-sDNA orders. RESULTS Nine hundred two patients with mt-sDNA orders were evaluated, of which 160/902 patients (17.7%) met at least 1 criterion for off-label mt-sDNA order. Increasing age was associated with off-label order (Odds Ratio [OR] 2.32 [95% CI, 1.86-2.89] for every 10-year increase in age, P < 0.0001). On multivariate analysis, increased age (OR 1.04 [1.02-1.06], P = 0.001) and need for diagnostic colonoscopy (OR 2.9 [1.01-8.34], P = 0.048) were associated with a positive mt-sDNA result. DISCUSSION Off-label mt-sDNA testing is common, and further efforts are needed to educate patients and providers on appropriate use of mt-sDNA for colorectal cancer screening.

BACKGROUND AND AIMSMethylation-based stool DNA test showed a promising application for colorectal cancer (CRC) detection. This study aimed to evaluate the performance of a novel dual-target stool DNA test (DT-sDNA), composed of SDC2 and TFPI2, for the detection of CRC in clinical practice by using large-scale data from a multicenter clinical trial.METHODSWe enrolled 1,164 participants from three independent hospitals, including 320 CRC patients, 148 adenomas, 396 interfering diseases and 300 healthy controls. Their stool samples were collected and tested paralleled by DT-sDNA test under the guidance of standard operating procedure. All participants were dichotomized as positive and negative according to the cycling threshold (Ct) values measured by quantitative methylation-specific PCR (MSP). The diagnostic performance of DT-sDNA test was assessed by calculating indexes of sensitivity, specificity, and overall coincidence rate. Sanger sequencing and retesting of resected participants were performed to verify the accuracy and effectiveness of the test.RESULTSOverall, the sensitivity, specificity, and total coincidence rate of DT-sDNA test for CRC detection were 95.31%, 88.39%, and 90.29%, respectively, with the kappa value of 0.775 (P < 0.05) when comparing to non-CRCs. The sensitivities for the detection of advanced adenomas (n=38) and non-advanced adenomas (n=110) were 63.16% and 33.64%, and the specificity was 96.67% for healthy normal controls. The methylation status of SDC2 and TFPI2 in 375 samples were verified by Sanger sequencing and the average coincidence rate reached 99.62%. The coincidence rate was 94.12% (n=32) for 34 participants that undertook DT-sDNA test again after surgical resection. These results demonstrated high accuracy of the DT-sDNA test in discriminating CRCs from other diseases and healthy controls.CONCLUSIONSThe novel DT-sDNA test showed good performance for the diagnosis of colorectal cancer in clinical practice; fda.hubei.gov.cn number; 20190020787.

The study was supported by Novartis, Sigrid Jusélius Foundation, and Cancer Society of Finland. The authors confirm that the funder had no influence over the study design, content of the article, or selection of this journal. Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer death worldwide. Early detection of CRC can improve patient survival rates; thus, the identification of noninvasive diagnostic markers is urgently needed. MicroRNAs (miRNAs) have extensive potential to diagnose several diseases, including cancer. In this study, we compared the expression pattern of miRNAs from plasma and stool samples of patients with early stages of CRC (I, II) with that of healthy subjects. We performed miRNA profiling using microarrays on plasma and stool samples of eight patients with CRC and four healthy subjects. Seven miRNAs were found to be underexpressed in both plasma and stool samples of patients with CRC versus healthy subjects. Then, we aimed to verify two out of these seven differentially expressed miRNAs (let-7a-5p and let-7f-5p) by quantitative reverse transcriptase polymerase chain reaction on a larger set of plasma and stool samples of 51 patients with CRC and 26 healthy subjects. We confirmed the results of microarray analysis since their expression was significantly lower in stool and plasma samples of patients with CRC. Moreover, receiver operating characteristic curve analysis demonstrated that fecal let-7f expression levels have significant sensitivity and specificity to distinguish between patients with CRC and healthy subjects. In conclusion, if the results are confirmed in larger series of patients, underexpressed let-7a-5p and let-7f-5p miRNAs in both plasma and stool samples of patients with CRC may serve potentially as noninvasive molecular biomarkers for the early detection of CRC.

To examine the impact of increasing multi-target stool DNA test (mt-sDNA [Cologuard]) utilization for colorectal cancer (CRC) screening in cohorts aged 50–75 and 45–75 years old with varying levels of adherence from the perspectives of integrated delivery networks (IDNs) and payers. We developed a budget impact model that simulates CRC screening with colonoscopy over a 10-year time horizon, fecal immunochemical test (FIT), and mt-sDNA according to the United States Preventive Services Task Force and American Cancer Society guidelines for average risk adults. We evaluated varying levels of screening adherence for a status quo scenario and for an increased mt-sDNA utilization scenario, from the IDN and payer perspectives. The IDN perspective included CRC screening program costs, whereas the payer perspective did not. Conversely, stool-based screening test and bowel preparation costs were unique to the payer perspective. The increased mt-sDNA scenarios yielded cost savings relative to the status quo under all adherence scenarios due to a decrease in screening and surveillance colonoscopies. For ages 50–75, in high and low adherence scenarios, savings were $19.8 M ($0.16 per-person-per-month (PPPM)) and $33.3 M ($0.28 PPPM) from the IDN perspective. From the payer perspective, savings were $4.2 M ($0.03 PPPM) and $6.7 M ($0.06 PPPM). For ages 45–75, in high and low adherence scenarios, cost savings were $19.3 M ($0.16 PPPM) and $33.0 M ($0.28 PPPM) from the IDN perspective and $3.9 M ($0.03 PPPM) and $6.2 M ($0.05 PPPM) from the payer perspective. In all imperfect adherence scenarios, the degree of cost-savings with increased mt-sDNA utilization correlated with the aggregate decrease in screening and surveillance colonoscopies. Estimates of real-world adherence levels were based on cross-sectional screening data from the literature, and assumptions were applied to individual screening modalities and screening scenarios. Among all adherence scenarios, perspectives, and age ranges, increased mt-sDNA utilization yielded cost-savings.

Early screening is an important way to reduce the incidence and mortality of colorectal cancer (CRC). Fecal DNA testing stands out among many screening methods due to its high sensitivity. However, at this stage, researchers have not found a high-efficiency method for fecal DNA extraction. To this end, this work carried out a new round of exploration. Here, this experiment synthesized a kind of nanomagnetic beads (NH2-SiO2@Fe3O4) with good stability for nucleic acid extraction. A comparative study with the centrifugal adsorption column method revealed the significant advantages of the magnetic bead method in extracting fecal DNA. The DNA extracted by the magnetic bead method is of high purity, can also achieve high-throughput tests, and is more suitable for polymerase chain reaction detection, greatly simplifying the stool DNA detection process and providing a basis for the widespread promotion of early screening.

AIM: There is not sufficient evidence about whether stool DNA methylation tests allow prioritizing patients to colonoscopy. Due to the COVID-19 pandemic, there will be a wait-list for rescheduling colonoscopies once the mitigation is lifted. The aim of this meta-analysis was to evaluate the accuracy of stool DNA methylation tests in detecting colorectal cancer. METHODS: The PubMed, Cochrane Library and MEDLINE via Ovid were searched. Studies reporting the accuracy (Sackett phase 2 or 3) of stool DNA methylation tests to detect sporadic colorectal cancer were included. The DerSimonian-Laird method with random-effects model was utilized for meta-analysis. RESULTS: Forty-six studies totaling 16 149 patients were included in the meta-analysis. The pooled sensitivity and specificity of all single genes and combinations was 62.7% (57.7%, 67.4%) and 91% (89.5%, 92.2%), respectively. Combinations of genes provided higher sensitivity compared to single genes (80.8% [75.1%, 85.4%] vs. 57.8% [52.3%, 63.1%]) with no significant decrease in specificity (87.8% [84.1%, 90.7%] vs. 92.1% [90.4%, 93.5%]). The most accurate single gene was found to be SDC2 with a sensitivity of 83.1% (72.6%, 90.2%) and a specificity of 91.2% (88.6%, 93.2%). CONCLUSIONS: Stool DNA methylation tests have high specificity (92%) with relatively lower sensitivity (81%). Combining genes increases sensitivity compared to single gene tests. The single most accurate gene is SDC2, which should be considered for further research.

Purpose of review In the United States, only 67% of patients are up to date with colorectal cancer (CRC) screening. While colonoscopy is highly sensitive and specific for CRC and precursor lesion detection and removal, it is invasive, expensive and resource heavy. Hence, there is an unfulfilled need for multiple modality CRC screening that can improve current CRC screening rates and may be resource effective strategies when used in conjunction with a colonoscopy program. Our review highlights the complementary, often underutilized, noninvasive CRC screening methods with a focus on performance, risks, benefits, and recent updates. Recent findings Studies demonstrate that fecal immunochemical testing (FIT) is superior to guaiac-based fecal occult blood tests for CRC screening. Studies show superiority of multitarget stool DNA test to FIT in sensitivity, though with concern for decreased specificity in setting of one-time tests. Technical advances continue to improve accuracy of colon capsule endoscopy. There are ongoing studies to characterize often difficult-to-detect high-risk lesions in computed tomography colonography. Septin 9 continues to have suboptimal accuracy for CRC screening, but has been shown to be associated with more advanced, invasive CRC stages. Summary There are ongoing advances in noninvasive screening modalities for CRC; these should be considered as alternatives to colonoscopy in specific patient populations.