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1.
J Cancer Educ ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39031303

ABSTRACT

Colorectal cancer (CRC) screening continues to be underutilized in the USA despite the availability of multiple effective, guideline-recommended screening options. Provider recommendation has been consistently shown to improve screening completion. Understanding how patient-provider communication influences CRC screening can inform interventions to improve screening completion. We developed a behavioral theory-informed survey to identify patient-provider communication factors associated with multi-target stool DNA (mt-sDNA) screening completion. The survey was administered by RTI International between 03/2022 and 06/2022 to a sample of US adults ages 45-75 who received a valid order for mt-sDNA screening with a shipping date between 5/2021 and 9/2021. Respondents completed an electronic or paper survey. Multivariable logistic regression was used to identify patient-provider communication factors associated with mt-sDNA test completion. A total of 2973 participants completed the survey (response rate, 21.7%) and 81.6% of them (n = 2427) reported having had a conversation with provider about mt-sDNA testing before the test was ordered. Having a conversation with the provider about the test, including discussions about costs, the need for follow-up testing and test instructions were associated with higher odds of test completion and being "very likely" to use the test in the future. Lack of discussion about advantages and disadvantages of available CRC screening options and lack of patient involvement in CRC screening decision-making were associated with reduced odds of test completion and likelihood of future use. Healthcare providers play a key role in patient adherence to CRC screening and must be appropriately prepared and resourced to educate and to engage patients in shared decision-making about CRC screening.

2.
Clin Gastroenterol Hepatol ; 21(6): 1627-1636.e4, 2023 06.
Article in English | MEDLINE | ID: mdl-36113828

ABSTRACT

BACKGROUND & AIMS: The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to stratify the risk of colorectal advanced neoplasm (AN). We aimed to evaluate the performance of the APCS score combined with a stool DNA test used for colorectal cancer screening. METHODS: A total of 2842 subjects who visited outpatient clinics or cancer screening centers were enrolled. Age, sex, smoking status, and family history were recorded and APCS scores were calculated in 2439 participants. A stool DNA test (SDC2 and SFRP2 tests) and fecal immunochemical test (FIT) were performed and colonoscopy was used as the gold standard among 2240 subjects who completed all study procedures. We used a threshold of 4.4 µg/g for the FIT, in addition to the manufacturer's recommended threshold of 20 µg/g to match the specificity of a stool DNA test. RESULTS: Based on the APCS score, 38.8% (946 of 2439) of the subjects were categorized as high risk, and they had a 1.8-fold increase in risk for AN (95% CI, 1.4-2.3) compared with low and moderate risk. The APCS combined with the stool DNA test detected 95.2% of invasive cancers (40 of 42) and 73.5% of ANs (253 of 344), while the colonoscopy workload was only 47.1% (1056 of 2240). The sensitivity for AN of APCS combined with stool DNA test was significantly higher than that of APCS combined with FIT (73.5% vs 62.8% with FIT cut-off value of 20 µg/g, and 73.5% vs 68.0% with FIT cut-off value of 4.4 µg/g; both P < .01). CONCLUSIONS: The APCS score combined with a stool DNA test significantly improved the detection of colorectal ANs, while limiting colonoscopy resource utilization (Chictr.org.cn, ChiCTR-DDD-17011169).


Subject(s)
Colorectal Neoplasms , Smoking , Humans , Asia , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Occult Blood , Early Detection of Cancer/methods , DNA , Feces , Mass Screening/methods
3.
Gastroenterology ; 162(3): 952-956, 2022 03.
Article in English | MEDLINE | ID: mdl-35094786

ABSTRACT

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update Commentary is to review the available evidence and provide expert advice regarding the approach to using noninvasive colorectal cancer (CRC) screening options, including evidence for their effectiveness, selection of individuals for whom these tests are appropriate, implications of a positive non-colonoscopy screening test, and opportunities to enhance the quality of noninvasive CRC screening programs. This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This expert commentary reflects recently published studies in this field, as well as the experiences of the authors who are gastroenterologists with high-level expertise in CRC screening and prevention.


Subject(s)
Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , DNA/analysis , Early Detection of Cancer/methods , Occult Blood , Adenoma/blood , Adenoma/urine , Colorectal Neoplasms/blood , Colorectal Neoplasms/urine , DNA/blood , DNA Methylation , Feces/chemistry , Humans , Patient Selection , Practice Guidelines as Topic , Risk Assessment , Septins/genetics
4.
Annu Rev Med ; 71: 59-69, 2020 01 27.
Article in English | MEDLINE | ID: mdl-31451044

ABSTRACT

Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies' assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80-90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.


Subject(s)
Colonic Polyps/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/prevention & control , DNA, Neoplasm/analysis , Early Detection of Cancer/methods , Feces , Aged , Cost-Benefit Analysis , Cross-Sectional Studies , Early Detection of Cancer/economics , Female , Humans , Male , Middle Aged , Precancerous Conditions/pathology , Sensitivity and Specificity
5.
BMC Gastroenterol ; 22(1): 191, 2022 Apr 18.
Article in English | MEDLINE | ID: mdl-35436855

ABSTRACT

BACKGROUND: Methylated SDC2 has been proved as a diagnostic marker for human colorectal cancer (CRC), noninvasive stool DNA-based methylation testing also emerges as a novel approach for detecting CRC. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test by a new qPCR detection reagent for early detection of CRC. METHODS: A new qPCR detection reagent contained two differentially methylated regions in SDC2 CpG islands for the detection of CRC was used in this study. Performance of the SDC2 methylation detection reagent was evaluated by analyzing limit of detection, precision, and specificity. The effect of interfering substances on assay performance was also tested. 339 subjects (102 CRC patients, 50 patients with advanced adenomas, 39 patients with non-advanced adenomas, 18 colitis patients and 130 normal individuals) from the China-Japan Friendship Hospital were evaluated. Approximately 2.5 g of stool sample was collected from each participant. Stool DNA was extracted and bisulfite-converted, followed by qPCR assay, which contained two pairs of primers for the methylation detection of two fragments of the SDC2 gene (named SDC2-A and SDC2-B). The diagnostic value of this test in CRC was evaluated by calculating receiver operating characteristic (ROC) curve, and value of the area under the curve (AUC). RESULTS: The test kit was able to detect methylated SDC2 in stool DNA samples with concentrations as low as 90 copies/µL in 100% of replicates. The sensitivity for detecting CRC by methylated SDC2-A alone was 85.29% (95% CI 77.03-91.00%) with a specificity of 96.15% (95% CI 91.08-98.58%). The sensitivity by methylated SDC2-B alone was 83.33% (95% CI 74.82-89.42%) with a specificity of 97.69% (95% CI 93.14-99.51%). However, when methylated SDC2-A and methylated SDC2-B were combined, the sensitivity for CRC detection improved to 87.25% (95% CI 79.27-92.53%) with a specificity of 94.62% (95% CI 89.11-97.56%). Further, the detection reagent achieved ROC-AUC 0.874 (95% CI 0.822-0.927) for SDC2-A, 0.906 (95% CI 0.859-0.952) for SDC2-B, and 0.939 (95% CI 0.902-0.977) for SDC2-Combine A&B. CONCLUSIONS: This study validated the capability of stool DNA-based SDC2 methylation test for early screening of CRC, and combined detection of two fragments of SDC2 gene could improve detection sensitivity.


Subject(s)
Adenoma , Colorectal Neoplasms , Adenoma/diagnosis , Adenoma/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , DNA/analysis , DNA Methylation , Early Detection of Cancer/methods , Feces/chemistry , Humans , Sensitivity and Specificity , Syndecan-2/genetics
6.
BMC Gastroenterol ; 22(1): 384, 2022 Aug 13.
Article in English | MEDLINE | ID: mdl-35963995

ABSTRACT

BACKGROUND: Stool DNA (sDNA) tests and fecal immunochemical test (FIT) are used for the detection of colorectal cancer (CRC). Here we performed a novel evaluation using sDNA and FIT to assess their performance in CRC screening and monitoring in Hubei, China. METHODS: Stool samples were collected from a high-risk population in Hubei, China (n = 359). sDNA tests and FIT were performed to test for KRAS mutations, NDRG4 and BMP3 methylation, and check hemoglobin levels. The methylation in BMP3 and NDRG4 genes was detected by TaqMan PCR method from human fecal samples. KRAS gene mutation in human fecal DNA was tested using TaqMan probe and amplification-refractory mutation system method. The colloid gold method was used for detection of hemoglobin in fecal samples. Finally, a novel evaluation by software was used to calculate the comprehensive value of the combined results for CRC detection and monitoring. RESULTS: The sensitivity and specificity of the novel evaluation for early CRC (stage I and II), advanced adenoma (AA), and non-colon cancer neoplasm (NA) detection were 95.45% and 81.6%, 29.63% and 75.9%, and 23.08% and 75.17%, respectively. The receiver operating characteristic (ROC) curves of the combined value for the above diseases were 0.945 ± 0.015, 0.543 ± 0.055, and 0.547 ± 0.038, respectively. The levels of the novel evaluation were not significantly associated with the pathology and stage (P > 0.05). In 20 out of 22 CRC patients, the novel evaluation of sDNA and FIT had decreased below threshold (< 165) at after surgery. DISCUSSION: The novel evaluation with sDNA test and FIT has increased sensitivity for screening of CRC and AA. The novel evaluation may have potential importance as an indicator of early CRC. Additionally, the dynamic changes of the comprehensive value after surgery were correlated with CRC treatment.


Subject(s)
Adenoma , Colorectal Neoplasms , Adenoma/diagnosis , Adenoma/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , DNA/analysis , DNA/genetics , Feasibility Studies , Hemoglobins/analysis , Humans , Proto-Oncogene Proteins p21(ras)/genetics
7.
Int J Colorectal Dis ; 37(6): 1231-1238, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35499710

ABSTRACT

PURPOSE: Molecular diagnostics of colorectal cancer (CRC) can be used as an auxiliary approach for patients recommended for colonoscopy, providing more CRC supplemental diagnosis options. This study investigated whether combined detection of KRAS/BRAF/APC mutation and SDC2/SFRP2 methylation can serve as auxiliary diagnostics in clinical management. METHODS: KRAS/BRAF/APC mutation and SDC2/SFRP2 methylation in stool samples from healthy donors, patients with CRC, advanced adenoma (AA), non-advanced adenoma (NAA), or other gastroenterological diseases were evaluated using quantitative PCR (qPCR) or methylation-specific quantitative PCR (MSP). Test accuracy was determined by evaluating the tests' sensitivity, specificity, positive/negative predictive value (PPV/NPV), or positive/negative likelihood ratio (PLR/NLR). RESULTS: The combined fecal KRAS/BRAF/APC mutation and SFRP2/SDC2 methylation detection test achieved a sensitivity of 88.57% with a PPV of 93.64% and a PLR of 7.10 for CRC patients. In comparison, the corresponding parameters for multigene mutation were 46.67%, 92.59%, and 36.26 and 83.81%, 93.94%, and 7.47, for DNA methylation, separately. The sensitivity of the combined test, gene mutation test, and DNA methylation test approach was 75%, 28.26%, and 72.83%. Furthermore, the specificity of this approach in the NAA group was 79.49%. Meanwhile, the overall diagnostic specificity for the combined test in NAA, healthy control, and interference groups was 88.42%. In addition, the sensitivity of the combined detection method increased with the disease stage in CRC patients and elevated along with the lesion size (≥ 1 cm) in AA patients. CONCLUSION: Combined detection of fecal KRAS/BRAF/APC mutation and SFRP2/SDC2 methylation has potential application value for the auxiliary diagnosis of CRC and AA.


Subject(s)
Adenoma , Colorectal Neoplasms , Adenoma/diagnosis , Adenoma/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Methylation/genetics , Early Detection of Cancer/methods , Feces , Humans , Membrane Proteins/genetics , Mutation/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Sensitivity and Specificity , Syndecan-2/genetics
8.
Curr Treat Options Oncol ; 23(4): 474-493, 2022 04.
Article in English | MEDLINE | ID: mdl-35316477

ABSTRACT

OPINION STATEMENT: Colorectal cancer (CRC) imposes significant morbidity and mortality, yet it is also largely preventable with evidence-based screening strategies. In May 2021, the US Preventive Services Task Force updated guidance, recommending screening begin at age 45 for average-risk individuals to reduce CRC incidence and mortality in the United States (US). The Task Force recommends screening with one of several screening strategies: high-sensitivity guaiac fecal occult blood test (HSgFOBT), fecal immunochemical test (FIT), multi-target stool DNA (mt-sDNA) test, computed tomographic (CT) colonography (virtual colonoscopy), flexible sigmoidoscopy, flexible sigmoidoscopy with FIT, or traditional colonoscopy. In addition to these recommended options, there are several emerging and novel CRC screening modalities that are not yet approved for first-line screening in average-risk individuals. These include blood-based screening or "liquid biopsy," colon capsule endoscopy, urinary metabolomics, and stool-based microbiome testing for the detection of colorectal polyps and/or CRC. In order to maximize CRC screening uptake in the US, patients and providers should engage in informed decision-making about the benefits and limitations of recommended screening options to determine the most appropriate screening test. Factors to consider include the invasiveness of the test, test performance, screening interval, accessibility, and cost. In addition, health systems should have a programmatic approach to CRC screening, which may include evidence-based strategies such as patient education, provider education, mailed screening outreach, and/or patient navigation, to maximize screening participation.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Early Detection of Cancer/methods , Humans , Mass Screening/methods , Middle Aged , Occult Blood , Sigmoidoscopy , United States
9.
Curr Gastroenterol Rep ; 22(7): 32, 2020 Jun 03.
Article in English | MEDLINE | ID: mdl-32494878

ABSTRACT

PURPOSE OF REVIEW: Participation goals for colorectal cancer (CRC) screening in the USA have not been met. Non-invasive screening strategies may improve CRC screening participation. We highlight recent literature on stool-based screening performance and expectations for emerging non-invasive screening tests. RECENT FINDINGS: Stool-based CRC screening detects screen-relevant colorectal neoplasia and outperforms a currently available plasma assay. Though modestly sensitive for CRC, adherence to annual fecal immunochemical testing (FIT) is sub-optimal. Multi-target stool DNA (MT-sDNA) has greater adherence, superior sensitivity for screen-relevant lesions (including those in the proximal colon and sessile serrated architecture), and equivalent specificity to FIT over a 3-year period. Stool-based CRC screening tests are anticipated to reduce the incidence and mortality of CRC through detection of early-stage cancers and high-risk polyps. These endpoints in performance will need to be met by emerging blood sample-based tests in order have meaningful impact in clinical practice.


Subject(s)
Colorectal Neoplasms/diagnosis , Early Detection of Cancer/standards , Feces/chemistry , Benchmarking , Colonic Polyps/diagnosis , Colonoscopy , Colorectal Neoplasms/blood , DNA, Neoplasm/analysis , DNA, Neoplasm/blood , Guideline Adherence , Humans , Immunochemistry , Mass Screening , Occult Blood , Patient Compliance , Septins/blood
10.
Scand J Gastroenterol ; 53(3): 273-278, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29313389

ABSTRACT

BACKGROUND AND AIM: Colonoscopic surveillance is recommended in patients with longstanding inflammatory bowel disease (IBD) as they are at increased risk of colorectal cancer (CRC). Non-invasive surveillance may improve compliance and access. Multi-target stool DNA (MT-sDNA) has been validated for screening of sporadic CRC but has not been assessed in IBD. Our aim was to assess the performance of a MT-sDNA test in a real-life surveillance setting of patients with longstanding IBD. MATERIAL AND METHODS: A total of 192 IBD patients enrolled from two prospective cohorts submitted an EDTA buffered stool sample and underwent chromo- or white light colonoscopy. Stools were assayed for methylated BMP3 & NDRG4, mutant KRAS and ß-actin by a laboratory blinded to clinical data. RESULTS: The multitarget-sDNA panel was positive in 2/2 CRC and 5/15 low-grade dysplasia (LGD) < 1 cm in diameter. Sensitivities were 100% (95% CI 16-100%) for CRC and 33% (95% CI 13-61%) for LGD lesions <1 cm, with specificities of 87% (95% CI 81-91%) and 93% (95% CI 88-96%), respectively. The estimated number of patients needed to screen to detect a single CRC was 96 (95% CI 93-99%) and was 28 (95% CI 22-34%) to detect any colorectal neoplasia (CRN). CONCLUSION: The MT-sDNA panel detected CRC in IBD. Sensitivity for sub-centimeter colorectal neoplasms in IBD patients appears similar to that observed in the general population. The test may be a valuable tool for detection of malignancy during structured surveillance of long-term IBD in a first line hospital setting.


Subject(s)
Colorectal Neoplasms/diagnosis , DNA, Neoplasm/analysis , Early Detection of Cancer/methods , Feces/chemistry , Inflammatory Bowel Diseases/complications , Adult , Aged , Aged, 80 and over , Colonoscopy , Colorectal Neoplasms/genetics , Cross-Sectional Studies , Female , Genetic Markers , Humans , Logistic Models , Male , Mass Screening , Middle Aged , Norway , Occult Blood , Prospective Studies , Sensitivity and Specificity , Young Adult
11.
Parasitology ; 145(7): 865-870, 2018 06.
Article in English | MEDLINE | ID: mdl-29113617

ABSTRACT

Cyclospora cayetanensis is a coccidian parasite associated with diarrheal illness. In the USA, foodborne outbreaks of cyclosporiasis have been documented almost every year since the mid-1990s. The typical approach used to identify this parasite in human stools is an examination of acid-fast-stained smears under bright-field microscopy. UV fluorescence microscopy of wet mounts is more sensitive and specific than acid-fast staining but requires a fluorescence microscope with a special filter not commonly available in diagnostic laboratories. In this study, we evaluated a new DNA extraction method based on the Universal Nucleic Acid Extraction (UNEX) buffer and compared the performances of four published real-time polymerase chain reaction (PCR) assays for the specific detection of C. cayetanensis in stool. The UNEX-based method had an improved capability to recover DNA from oocysts compared with the FastDNA stool extraction method. The best-performing real-time PCR assay was a C. cayetanensis-specific TaqMan PCR that targets the 18S ribosomal RNA gene. This new testing algorithm should be useful for detection of C. cayetanensis in human stool samples.


Subject(s)
Cyclospora/isolation & purification , Cyclosporiasis/diagnosis , DNA, Protozoan/isolation & purification , Feces/parasitology , Real-Time Polymerase Chain Reaction , Cyclospora/genetics , Cyclosporiasis/parasitology , Humans , Molecular Diagnostic Techniques , Oocysts/genetics , RNA, Ribosomal, 18S/isolation & purification
12.
BMC Cancer ; 17(1): 112, 2017 Feb 07.
Article in English | MEDLINE | ID: mdl-28173773

ABSTRACT

BACKGROUND: Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach. We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires. METHODS/DESIGN: This prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived ≥8 years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6-8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and molecular analyses in order to obtain more insight into colorectal carcinogenesis in Hodgkin lymphoma survivors. The Miscan-model will be used for cost-effectiveness analyses. DISCUSSION: Evaluation of the diagnostic performance, patient acceptance and burden of colorectal cancer surveillance is necessary for future implementation of an individualized colorectal cancer surveillance program for Hodgkin lymphoma survivors. In addition, more insight into treatment-induced colorectal carcinogenesis will provide the first step towards prevention and personalized treatment. This information may be extrapolated to other groups of cancer survivors. TRIAL REGISTRATION: Registered at the Dutch Trial Registry (NTR): NTR4961 .


Subject(s)
Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/economics , Hodgkin Disease/drug therapy , Neoplasms, Second Primary/diagnosis , Procarbazine/adverse effects , Research Design , Adenoma/chemically induced , Adolescent , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Protocols , Colonoscopy , Colorectal Neoplasms/chemically induced , Cost-Benefit Analysis , DNA, Neoplasm/analysis , Early Detection of Cancer/methods , Feces/chemistry , Hodgkin Disease/radiotherapy , Humans , Immunochemistry , Middle Aged , Neoplasms, Second Primary/chemically induced , Procarbazine/therapeutic use , Prospective Studies , Survivors , Young Adult
13.
BMC Cancer ; 17(1): 116, 2017 Feb 07.
Article in English | MEDLINE | ID: mdl-28173852

ABSTRACT

BACKGROUND: As in many other European countries, a nationwide screening program for colorectal cancer (CRC) has recently been introduced in the Netherlands. As a side effect, such a screening program will inherently yield an increase in the demand for surveillance after removal of polyps/adenomas or CRC. Although these patients are at increased risk of metachronous colorectal neoplasia, solid evidence on CRC-related mortality reduction as a result of colonoscopy-based surveillance programs is lacking. Furthermore, colonoscopy-based surveillance leads to high patient burden, high logistic demands and high costs. Therefore, new surveillance strategies are needed. The aim of the present study, named Molecular stool testing for Colorectal CAncer Surveillance (MOCCAS), is to determine the performance characteristics of two established non-invasive tests, i.e., the multitarget stool DNA test Cologuard® and the faecal immunochemical test (FIT) in the detection of CRC and advanced adenomas as an alternative for colonoscopy surveillance. METHODS: In this observational cross-sectional cohort study, subjects aged 50 to 75 years will be approached to collect (whole-) stool samples for molecular testing and a FIT prior to their scheduled surveillance colonoscopy. The results of the tests will allow calculation of test sensitivities and specificities in the context of surveillance. This will provide the required input for the Dutch ASCCA model (Adenoma and Serrated pathway to Colorectal CAncer) to simulate surveillance strategies differing in frequency and duration. The model will allow predictions of lifetime health effects and costs. Multiple centres in the Netherlands will participate in the study that aims to include 4,000 individuals. DISCUSSION: The outcome of this study will inform on the (cost-) effectiveness of stool based molecular testing as an alternative for colonoscopy in the rapidly expanding surveillance population. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ): NCT02715141 . Retrospectively registered 17 February 2016.


Subject(s)
Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , DNA, Neoplasm/analysis , Early Detection of Cancer/methods , Feces/chemistry , Immunochemistry , Research Design , Adenoma/metabolism , Adenoma/pathology , Aged , Cohort Studies , Colonoscopy , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Cross-Sectional Studies , Early Detection of Cancer/economics , Humans , Middle Aged , Netherlands , Sensitivity and Specificity
14.
Gastroenterology ; 149(5): 1286-93, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26033632

ABSTRACT

Colorectal cancer (CRC) screening has been shown to reduce CRC incidence and mortality and is widely recommended. However, despite the demonstrated benefits of screening and ongoing efforts to improve screening rates, a large percentage of the population remains unscreened. Noninvasive stool based tests offer great opportunity to enhance screening uptake. The evidence supporting the use of both fecal immunochemical testing (FIT) and stool DNA (sDNA) has been growing rapidly and both tests are now commercially available for use. Other stool biomarkers (eg, RNA and protein based) are also actively under study both for use independently and as adjuncts to the currently available tests. This mini review provides current, state of the art knowledge about noninvasive stool based screening. It includes a more detailed examination of those tests currently in use (ie, FIT and sDNA) but also provides an overview of stool testing options under development (ie, protein and RNA).


Subject(s)
Biomarkers/metabolism , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/metabolism , Early Detection of Cancer/methods , Feces , Mass Screening/methods , Humans , Immunochemistry/methods
15.
Curr Gastroenterol Rep ; 18(6): 30, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27165404

ABSTRACT

Colorectal cancer (CRC) screening reduces CRC incidence and mortality and is widely recommended. However, despite these demonstrated benefits, a large percentage of the population remains unscreened. The multi-target stool DNA (MT-sDNA) test is a new, non-invasive option for CRC screening that has a high accuracy rate in detection of colorectal neoplasia and offers great opportunity to enhance screening uptake. This review provides the current state of the art knowledge about the use of MT-sDNA in CRC screening.


Subject(s)
Colorectal Neoplasms/diagnosis , DNA, Neoplasm/analysis , Early Detection of Cancer/methods , Feces/chemistry , Colorectal Neoplasms/genetics , Humans , Mass Screening/methods , Precancerous Conditions/diagnosis , Precancerous Conditions/genetics , Sensitivity and Specificity
16.
Dig Dis Sci ; 61(1): 117-25, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26297132

ABSTRACT

BACKGROUND: Stool DNA testing represents a potential noninvasive approach to detect upper gastrointestinal (UGI) neoplasms. However, little is known about fecal recovery efficiency of DNA exfoliated from UGI tumors. AIMS: The purpose of this study was to establish a human ingestion model that quantitatively approximates daily cellular shedding from UGI neoplasms and to estimate fecal DNA marker recovery rates. METHODS: Healthy volunteers (n = 10) ingested two scheduled doses of raw salmon, 0.3 and 30 g, simulating the mass exfoliated daily from 1 to 4.5 cm lesions. To approach a steady-state, each dose was ingested over three consecutive days in randomized order. Following defecation of an indicator dye ingested with test meals, stools were collected over 48 h. Ingested salmon DNA was captured from stools using probes targeting pathognomonic Salmonidae sequences (SlmII). Captured DNA was quantified using PCR primers to generate 178, 138, 88 and 55 bp amplicons. RESULTS: SlmII sequences were recovered from all stools following salmon ingestion; recovery was proportional to amount ingested (p = 0.004). Fecal recovery of ingested salmon varied inversely with amplicon size targeted; mean recovery rates of SlmII were 0.49, 0.91, 3.63, and 7.31 copies per 100,000 copies ingested for 178, 134, 88, and 55 bp amplicons, respectively (p < 0.0001). Longer oro-anal transit was associated with reduced recovery. CONCLUSIONS: While recovery efficiencies are low, ingested cellular DNA simulating daily amounts shed from UGI tumors can readily be detected in stool. Assay of shorter-fragment analyte increases recovery. This ingestion model has potential value in studying the effects of perturbations relevant to the fecal recovery of DNA exfoliated from UGI tumors.


Subject(s)
DNA, Neoplasm/metabolism , Feces/chemistry , Gastrointestinal Neoplasms/diagnosis , Polymerase Chain Reaction , Salmon/genetics , Seafood , Animals , DNA, Neoplasm/isolation & purification , Female , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/metabolism , Healthy Volunteers , Humans , Male , Predictive Value of Tests , Time Factors
17.
Soc Sci Med ; 340: 116397, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38043438

ABSTRACT

Colorectal cancer (CRC) screening continues to be underutilized in the US despite the availability of multiple effective, guideline-recommended screening options. Provider recommendation has been consistently shown to improve screening completion. Yet, available literature provides little information as to how specific information providers communicate influence patient decision-making about CRC screening. We tested the pathways through which information communicated by providers about the "Why" and "How" of CRC screening using the mt-sDNA test contributes to intention to complete the test. Data came from a behavioral theory-informed survey that we developed to identify psychosocial factors associated with mt-sDNA screening. RTI International administered the survey between 03/2022-06/2022 to a sample of US adults ages 45-75 who received a valid order for mt-sDNA screening with a shipping date between 5/2021-9/2021. Participants completed an electronic or paper survey. We tested the proposed relationships using structural equation modeling and tested indirect effects using Monte Carlo method. A total of 2,973 participants completed the survey (response rate: 21.7%) and 81.6% (n = 2,427) reported have had a conversation with their health care provider about mt-sDNA screening before the test was ordered. We found that "Why" information from providers was positively associated with perceived effectiveness of mt-sDNA screening, while "How" information was positively associated with perceived ease of use. "Why" information contributed to screening intention through perceived effectiveness while "How" information contributed to screening intention through perceived ease of use. These findings emphasize the critical role of provider communication in shaping patient decision-making regarding CRC screening. CRC screening interventions could consider implementing provider-patient communication strategies focusing on improving patient understanding of the rationale for CRC screening and the effectiveness of available screening options as well as addressing barriers and enhancing patients' self-efficacy in completing their preferred screening option.


Subject(s)
Colorectal Neoplasms , Mass Screening , Adult , Humans , Behavior Control , Intention , Early Detection of Cancer , Feces/chemistry , Communication , Colorectal Neoplasms/diagnosis
18.
Clin Gastroenterol Hepatol ; 11(10): 1313-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23639600

ABSTRACT

BACKGROUND & AIMS: Colorectal cancer (CRC) and advanced precancers can be detected noninvasively by analyses of exfoliated DNA markers and hemoglobin in stool. Practical and cost-effective application of a stool DNA-based (sDNA) test for general CRC screening requires high levels of accuracy and high-capacity throughput. We optimized an automated sDNA assay and evaluated its clinical performance. METHODS: In a blinded, multicenter, case-control study, we collected stools from 459 asymptomatic patients before screening or surveillance colonoscopies and from 544 referred patients. Cases included CRC (n = 93), advanced adenoma (AA) (n = 84), or sessile serrated adenoma ≥1 cm (SSA) (n = 30); controls included nonadvanced polyps (n = 155) or no colonic lesions (n = 641). Samples were analyzed by using an automated multi-target sDNA assay to measure ß-actin (a marker of total human DNA), mutant KRAS, aberrantly methylated BMP3 and NDRG4, and fecal hemoglobin. Data were analyzed by a logistic algorithm to categorize patients as positive or negative for advanced colorectal neoplasia (CRC, advanced adenoma, and/or SSA ≥1 cm). RESULTS: At 90% specificity, sDNA analysis identified individuals with CRC with 98% sensitivity. Its sensitivity for stage I cancer was 95%, for stage II cancer it was 100%, for stage III cancer it was 96%, for stage IV cancer it was 100%, and for stages I-III cancers it was 97% (nonsignificant P value). Its sensitivity for advanced precancers (AA and SSA) ≥1 cm was 57%, for >2 cm it was 73%, and for >3 cm it was 83%. The assay detected AA with high-grade dysplasia with 83% sensitivity. CONCLUSIONS: We developed an automated, multi-target sDNA assay that detects CRC and premalignant lesions with levels of accuracy previously demonstrated with a manual process. This automated high-throughput system could be a widely accessible noninvasive approach to general CRC screening.


Subject(s)
Automation, Laboratory/methods , Biomarkers, Tumor/analysis , Colorectal Neoplasms/diagnosis , DNA/isolation & purification , Feces/chemistry , Hemoglobins/analysis , Molecular Diagnostic Techniques/methods , Adult , Aged , Aged, 80 and over , Case-Control Studies , DNA/genetics , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Single-Blind Method
19.
Int J Med Sci ; 10(3): 230-4, 2013.
Article in English | MEDLINE | ID: mdl-23372428

ABSTRACT

BACKGROUND: Analysis of aberrant hypermethylation in stool DNA might provide a novel strategy for noninvasive detection of colorectal cancer. AIMS: To explore the feasibility of detecting hypermethylation in Spastic paraplegia-20 promoter as a stool-based DNA marker for detection of colorectal cancer. METHODS: We collected 96 tissue and stool samples from patients with colorectal cancer and 30 stool samples healthy individuals. RESULTS: Hypermethylated Spastic paraplegia-20 occurs in 85.4% (82/96) of patients with colorectal cancer in the tissue samples. In the stool samples, the results indicate 80.2% (77/96) sensitivity and 100% (30/30) specificity of the test for detecting colorectal cancer by using the stool samples as a noninvasive method. CONCLUSIONS: The study reveals that hypermethylation in Spastic paraplegia-20 promoter is a highly specific and sensitive biomarker for screening colorectal cancer in stool samples as a noninvasive method.


Subject(s)
Colorectal Neoplasms , DNA/genetics , Paraplegia , Proteins/genetics , Aged , Cell Cycle Proteins , Colorectal Neoplasms/complications , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , DNA Methylation/genetics , Early Detection of Cancer , Feces/chemistry , Female , Humans , Male , Middle Aged , Paraplegia/complications , Paraplegia/diagnosis , Paraplegia/genetics , Promoter Regions, Genetic
20.
Cancer Med ; 12(7): 7689-7698, 2023 04.
Article in English | MEDLINE | ID: mdl-36468523

ABSTRACT

BACKGROUND: Stool DNA test has been emerged as an effective noninvasive method for colorectal cancer (CRC) screening, but the real-world performance of stool DNA test in Chinese population has rarely been reported. METHODS: A total of 36,527 subjects were recruited in Haining City from January 2021 to December 2021. Participants underwent primary screening by taking both two-samples fecal immunochemical tests (FITs) and high-risk factor questionnaire (HRFQ), and those who tested either positive by FITs or evaluated to be high risk by HRFQ were recommended to undertake subsequent stool DNA test and colonoscopy. RESULTS: Of 36,527 participants, 34,778 (95%) completed both HRFQ and FITs, 9947 (29%) showed positive results during primary screening, and the colonoscopy compliance rate was 49%. Of primary screening positives, 8733 (88%) completed stool sample collections, and colonoscopy results from 4293 eligible participants were used for analyzing the performance of stool DNA test. The sensitivities for detecting CRC and advanced adenomas (AA) were 100% (95% CI: 60-100%) and 40% (95% CI: 34-46%), and the area under curve (AUC) was 0.961 (95% CI:0.954-0.967) and 0.625 (95% CI: 0.609-0.641), respectively. The specificity of stool DNA test was 84% (95% CI: 82-85%). The false-positive rate for stool DNA test is about 10% less than that of primary screening. CONCLUSION: Stool DNA test is a cost-effective and promising alternative strategy for CRC screening in China.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Humans , Sensitivity and Specificity , Early Detection of Cancer/methods , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/epidemiology , DNA , Mass Screening/methods
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