Original article
Diagnostic accuracy of multitarget stool DNA testing for colorectal cancer screening: A systematic review and meta-analysis
Precisión diagnóstica de las pruebas de DNA en heces con objetivos múltiples para la detección del cáncer colorrectal: una revisión sistemática y un metaanálisis
Roya Dolatkhaha,
, Saeed Dastgirib, Mohammad Asghari Jafarabadic,d,e, Hossein Mashhadi Abdolahif, Mohammad Hossein Somig,
Corresponding author
Corresponding author
a Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
b Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
c Cabrini Research, Cabrini Health, Australia
d School of Public Health and Preventative Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia
e Road and Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
f Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
g Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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(A) The expression level of circ-001241 in liver cancer cells stably transfected with circ-001241 or blank vector plasmid was detected by RT-qPCR. (B, C) Circ-001241 or vector transfected cells were treated with sorafenib at different doses, and the survival rate of cells was observed by CCK-8 method 48<span class="elsevierStyleHsp" style=""></span>h later. (D) Colony formation assay of HCC cells transfected with circ-001241or vector after sorafenib (2<span class="elsevierStyleHsp" style=""></span>μM) treatment for 48<span class="elsevierStyleHsp" style=""></span>h. (E) The apoptosis levels in HCC cells transfected with circ-001241or vector after sorafenib (2<span class="elsevierStyleHsp" style=""></span>μM) treatment for 48<span class="elsevierStyleHsp" style=""></span>h were observed by flow cytometry. 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"idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Diagnostic accuracy of multitarget stool DNA testing for colorectal cancer screening: A systematic review and meta-analysis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "753" "paginaFinal" => "766" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Roya Dolatkhah, Saeed Dastgiri, Mohammad Asghari Jafarabadi, Hossein Mashhadi Abdolahi, Mohammad Hossein Somi" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Roya" "apellidos" => "Dolatkhah" "email" => array:1 [ 0 => "royadolatkhah@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Saeed" "apellidos" => "Dastgiri" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Mohammad Asghari" "apellidos" => "Jafarabadi" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0035" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0040" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Hossein Mashhadi" "apellidos" => "Abdolahi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0020" ] ] ] 4 => array:4 [ "nombre" => "Mohammad Hossein" "apellidos" => "Somi" "email" => array:1 [ 0 => "mhosseinsina@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Cabrini Research, Cabrini Health, Australia" "etiqueta" => "c" "identificador" => "aff0035" ] 3 => array:3 [ "entidad" => "School of Public Health and Preventative Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia" "etiqueta" => "d" "identificador" => "aff0040" ] 4 => array:3 [ "entidad" => "Road and Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran" "etiqueta" => "e" "identificador" => "aff0015" ] 5 => array:3 [ "entidad" => "Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran" "etiqueta" => "f" "identificador" => "aff0020" ] 6 => array:3 [ "entidad" => "Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran" "etiqueta" => "g" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding authors." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Precisión diagnóstica de las pruebas de DNA en heces con objetivos múltiples para la detección del cáncer colorrectal: una revisión sistemática y un metaanálisis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1294 "Ancho" => 2917 "Tamanyo" => 206680 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Summary receiver operating characteristic plot (SROC), of the Mt-SDNA test screening tests diagnostic accuracy for: (A) cancer, (B) advanced adenoma, (C) combined CRC and AA detection, graphical summaries of the fitted model.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">According to the latest Global Cancer Statistics, colorectal cancer (CRC) is the third most common cancer, but is the second leading cause of cancer-related death, worldwide.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a> The incidence of colorectal cancer vary widely across different regions of the world, as it was about 9-fold variation, and 4-fold higher in transitioned countries as well.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1,2</span></a> Socioeconomic development, lack of CRC screening and early diagnosis programs, and westernization of most developed countries recently leaded to an increasing trends of incidence and mortality in low and lower-middle income countries.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1–3</span></a> However there was declines in both CRC incidence and mortality in most developed countries because of implementation of screening programs including colonoscopy and removal of precancerous lesions, healthy lifestyle choices, declines in smoking, and best practices in early detection and treatment of CRC.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">CRC screening programs, which lead to early detection, can reduce approximately 60% of CRC-related deaths. Recent studies have shown that 60–70% of CRC cases can be diagnosed at an early stage of the disease by screening and early diagnostic techniques, including colonoscopy.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">4,5</span></a> This allows the diagnosis of cancer in the curable stage and also decreases the CRC incidence in average-risk individuals.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a> Screening strategies should therefore include a standard screening method to detect precancerous lesions in asymptomatic individuals, identifying those eligible for screening by risk assessment.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Increased knowledge on specific changes and molecular pathways underlying CRC malignancy has led to the development of new laboratory-based diagnostic tests, including molecular and immunologic methods, in recent years. Compared with colonoscopy as an approved gold standard method for CRC screening in many centers, new techniques are non-invasive, simple, and patient friendly. According to the last released guidelines of American Cancer Society's in 2018, U.S. Preventive Services Task Force in 2016, and the National Comprehensive Cancer Network in 2016, multi-target stool DNA (Mt-sDNA) tests (combined Fecal Immunochemical Test (FIT)-DNA stool tests) every 3-years have been recommended as a potential screening method in average-risk populations, with almost the same results in CRC incidence reduction compared with 10-year colonoscopy (63% vs. 65%).<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">6,8,9</span></a> Most recently United State (US) Preventative Services Task Force has been endorsed Mt-sDNA test as first-line CRC screening test, as this test is cost effective compared with no screening, and is enough efficient compared with other screening modalities.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> Therefore, Mt-sDNA-based testing may be a good substitute for individuals unable to undergo colonoscopy because of possible harm, unavailability, and unpleasant and time-consuming cathartic bowel preparation.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a> However, colonoscopy is strongly recommended for individuals with abnormal findings in any other screening method, including sigmoidoscopy, CT colonoscopy, and stool-based methods including Guaiac Fecal Occult Blood Test (FOBT), Fecal Immunochemical Test (FIT), and stool DNA test. Although different screening modalities were presented in majority of guideline, however there is still discrepancy with regards to the respective role, ranking and cost effectiveness of these tests.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">8,9,12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Therefore, we performed a systematic review and meta-analysis of the most reliable published evidence on the diagnostic accuracy of Mt-sDNA tests compared with colonoscopy during the last 20 years. This information will aid clinical decision-making.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We designed and performed this study as a systematic review and meta-analysis following the PRISMA guidelines.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Eligibility criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">The systematic review question was the effectiveness of Stool-based DNA tests for detecting CRC and any other pre-cancerous lesions (advanced adenoma) compared with colonoscopy as a gold standard method in a normal population (asymptomatic persons with an average risk of developing CRC).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Information sources</span><p id="par0035" class="elsevierStylePara elsevierViewall">We searched all available databases including PubMed, MEDLINE, CINAHL Plus with full text (EBSCO), Web of Science Core Collection, EMBASE (Ovid), SCOPUS, ProQuest Central, Joanna Briggs Institute EBP database, and Google Scholar, as well as SID, Magiran, Medlib, and Irandoc as Iranian databases.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Search strategy</span><p id="par0040" class="elsevierStylePara elsevierViewall">We used Boolean Logics, including the following key words:</p><p id="par0045" class="elsevierStylePara elsevierViewall">“Colorectal”, “Cancer”, “Malignancy”, “Neoplasm”, “Screening”, “Early Detection”, “Colonoscopy”, “Stool based tests”, “Stool DNA Test”, “Mt-sDNA-based testing”.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In addition, we used the methods “snowballing” (search for related articles or similar results), the “ancestry” method (follow up on citations in selected publications), and use the “cited references”. In some cases, we contacted the study authors to identify additional studies.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Selection process</span><p id="par0055" class="elsevierStylePara elsevierViewall">We selected studies according to our defined PICOS items, first from Title and Abstracts, and then from the text of the manuscripts. All manuscripts were screened for eligibility according to PICOS criteria, time of publication, and type of study. Studies with reliable and available end points (sensitivity (SE), specificity (SP), true positives (tp), false positives (fp), false negatives (fn), true negatives (tn), number of individuals with disease (CRC and AA), and number of healthy controls were included in the meta-analysis.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Criteria for considering studies for this review were as follows:</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">PICOS</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Participants</span><p id="par0065" class="elsevierStylePara elsevierViewall">Normal population (average risk of developing CRC).</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Intervention</span><p id="par0070" class="elsevierStylePara elsevierViewall">Stool based DNA test panel compared with colonoscopy.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Panel includes mutational aberrations including Kirsten rat sarcoma viral oncogene homolog (KRAS) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and/or hyper methylated promoter genes including Secreted Frizzled-Related Protein-2 (SFRP2), Tissue factor pathway inhibitor 2 (TFPI2), Bone morphogenetic protein 3 (BMP3), N-Myc downstream regulated gene 4 (NDRG4), Tissue factor pathway inhibitor 2 (TFPI2), and vimentin) as well as Fecal Immunochemical Test (FIT, any brand)</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Control/compare</span><p id="par0080" class="elsevierStylePara elsevierViewall">Optical colonoscopy (gold standard method).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Outcome</span><p id="par0085" class="elsevierStylePara elsevierViewall">Detecting any<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1)</span><p id="par0090" class="elsevierStylePara elsevierViewall">Precancerous lesions (AA)</p></li></ul></p><p id="par0095" class="elsevierStylePara elsevierViewall">AA:</p><p id="par0100" class="elsevierStylePara elsevierViewall">An AA was defined as<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">an adenoma 10<span class="elsevierStyleHsp" style=""></span>mm or</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">an adenoma with villous histology (25% villous)</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">and/or high-grade dysplasia of any size.</p></li></ul><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">2)</span><p id="par0120" class="elsevierStylePara elsevierViewall">Neoplastic lesions (including carcinoma in situ early stage or advanced CRC)</p></li></ul></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Setting</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Clinical validity</span><p id="par0125" class="elsevierStylePara elsevierViewall">Test accuracy and reliability in detecting CRC and/or AA (Clinical sensitivity and specificity; predictive value)</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Publication date</span><p id="par0130" class="elsevierStylePara elsevierViewall">Published in the last 20 years</p><p id="par0135" class="elsevierStylePara elsevierViewall">Publication language: English</p><p id="par0140" class="elsevierStylePara elsevierViewall">We did not consider any geographic restraints in the search strategy.</p></span></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Data collection process</span><p id="par0145" class="elsevierStylePara elsevierViewall">Two main investigators (RD, SD) performed the appraisal of the included manuscript and data collection independently, according to our eligibility criteria.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Data items</span><p id="par0150" class="elsevierStylePara elsevierViewall">Studies with reliable and available end points (SE, SP, true positives (tp), false positives (fp), false negatives (fn), true negatives (tn), number of individuals with disease (CRC and AA), and number of healthy controls were included in the meta-analysis.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Study risk of bias assessment</span><p id="par0155" class="elsevierStylePara elsevierViewall">The risk of bias was assessed using the Cochrane Collaboration tool,<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> which included six domains, including reporting bias, attrition bias, performance bias, detection bias, selection bias, and other bias. Accordingly, each domain was assessed as having a low, unclear, or high risk of bias.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Effect measures</span><p id="par0160" class="elsevierStylePara elsevierViewall">For the meta-analysis of the diagnostic accuracy of Mt-sDNA test for detecting CRC and AA compared with colonoscopy, hierarchical logistic regression and the HSROC (hierarchical summary receiver operating characteristic) model were applied.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a> The summary measures were sensitivity and specificity, positive and negative likelihood ratios, and diagnostic odds ratios.</p><p id="par0165" class="elsevierStylePara elsevierViewall">The primary dataset was designed for analysis including true positives (tp), false positives (fp), false negatives (fn), true negatives (tn), number of individuals with disease (CRC and AA), and number of healthy controls.</p><p id="par0170" class="elsevierStylePara elsevierViewall">The summary receiver operating characteristic curves (SROC) were applied to simplify the graphical summaries for the fitted model, summary points and confidence regions. The size of each circle shows the total number of cases in each study. The size of each point was scaled according to the precision of sensitivity and specificity in the study. The solid circle (summary point) represents the summary estimate of the sensitivity and specificity of the related test. The summary point is surrounded by a dotted line representing the 95% confidence region and a dashed line representing the 95% prediction region. Finally, a summary curve from the HSROC model was obtained.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Synthesis methods</span><p id="par0175" class="elsevierStylePara elsevierViewall">The quantity <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> was used to assess the impact of unobserved heterogeneity across studies that are attributed to the heterogeneity between studies rather than to chance.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a> A mixed model was used to express both the intra-class correlation coefficient (ICC) and Midas (MED) sensitivity and specificity separately as percentages with 95% confidence intervals (CIs). In addition, the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">value</span></span> ranged from 0 to 100, while 0% indicated no observed heterogeneity and an increase in the value greater than 75% was considered as substantial heterogeneity between studies. All analyses were performed using STATA MP 14.2 (StataCorp LP, College Station, TX 77845, USA) software. Inter-study variation in sensitivity and specificity, receiver operating characteristic (ROC) Area with 95% CI, heterogeneity (using Chi-squared test), and inconsistency (using the <span class="elsevierStyleItalic">I</span>-squared test) were performed using the “midas” method. The reference test was colonoscopy and the index tests were Mt-sDNA and FIT tests.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Reporting bias assessment</span><p id="par0180" class="elsevierStylePara elsevierViewall">Publication bias across the studies was assessed with Deek's asymmetry test, which performs a linear regression of the log odds ratios on the inverse root of effective sample sizes as a test for funnel plot asymmetry in the diagnostic meta-analysis.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">18</span></a> A non-zero slope coefficient is suggestive of a significantly small study bias (<span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.10).</p></span></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Results</span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Study selection</span><p id="par0185" class="elsevierStylePara elsevierViewall">An advanced search in all available databases using intended keywords found 450 published manuscripts in the PubMed database, 89 in EBSCO, 243 in Web of Science Core Collection, 432 in EMBASE (Ovid), 87 in SCOPUS, 80 in Google Scholar, and 40 in Iranian databases (SID, Magiran, Medlib, and Irandoc). Meanwhile, 54 studies were selected by a search of manuscript bibliographies. A total of 1475 published studies were screened and assessed for eligibility. Of these studies, 987 were selected based on our inclusion criteria. Records were screened independently by two co-investigators for reliability and data quality, and after excluding 256 duplicates, finally, 11 full text articles were included in the review and quantitative analysis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Study characteristics</span><p id="par0190" class="elsevierStylePara elsevierViewall">The information of included studies is summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Risk of bias in studies</span><p id="par0195" class="elsevierStylePara elsevierViewall">The risk of bias was assessed in the clinical trials. An unclear risk of selection bias (due to lack of information on the method of randomization and concealment), performance bias (due to lack of information on blind assessments), and detection bias (blinded outcome assessment) was observed. The risk of bias for the included studies was low for reporting bias, attrition bias, and other sources of bias (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Results of individual studies</span><p id="par0200" class="elsevierStylePara elsevierViewall">For the Mt-sDNA diagnostic test accuracy, 11 studies were included in the meta-analysis. For the FIT diagnostic accuracy test, 6 studies were included. Results of Mt-SDNA and FIT tests underwent total and subgroup analysis for CRC and AA and for combined CRC and AA diagnostic accuracy compared with colonoscopy (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Mt-sDNA test subgroup</span><p id="par0205" class="elsevierStylePara elsevierViewall">Eleven studies achieved the eligibility to be included in the diagnostic accuracy meta-analysis. The total number of CRC patients in the 11 studies ranged from 7 to 435 cases, and AA patients from 11 to 757 cases, while the control groups were between 28 and 4457 people. There were two outcome analyses for ten studies (CRC and AA), and one study only had diagnostic tests for CRC cases in the dataset.</p><p id="par0210" class="elsevierStylePara elsevierViewall">The results showed that the sensitivity of Mt-sDNA test for CRC diagnosis ranged between 100%,<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> and 18%.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> The specificity was at its highest in the Redwood et al., 2020 study (99%),<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> and lowest in the Park et al., 2017 study (55%).<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">FIT test subgroup</span><p id="par0215" class="elsevierStylePara elsevierViewall">Six studies were eligible for inclusion in the diagnostic accuracy meta-analysis. The total number of CRC patients in the six studies ranged from 7 to 252, AA from 20 to 757, and healthy controls from 102 to 4454.</p><p id="par0220" class="elsevierStylePara elsevierViewall">There were two outcome analyses for four studies (CRC and AA), and two studies only had diagnostic tests for CRC cases in the dataset. The sensitivity of the FIT test for CRC diagnosis ranged from 100%,<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a> to 13%.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> The specificity was the highest in the Redwood et al. (2016) study (99%),<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> and lowest in the Sun et al. (2019) (80%) study.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a></p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Results of synthesis</span><p id="par0225" class="elsevierStylePara elsevierViewall">Meta-analysis results of the Mt-sDNA test showed that the combined sensitivity for diagnosis was 89% for CRC (95% CI: 0.76–0.96), 51% for AA (95% CI: 0.39–0.63), and 76% for combined CRC and AA (95% CI: 0.61–0.86). Combined specificity was 91% (95% CI: 0.86–0.95) for CRC, 89% (95% CI: 0.84–0.92) for AA, and 90% (95% CI: 0.87–0.93) for combined CRC and AA.</p><p id="par0230" class="elsevierStylePara elsevierViewall">The diagnostic odds ratio of the Mt-sDNA test was 87.42 for CRC (95% CI: 31.79–240.43), 8.46 for AA (95% CI: 5.59–12.81), and 87.42 for combined CRC and AA (95% CI: 31.79–240.43).</p><p id="par0235" class="elsevierStylePara elsevierViewall">The results are presented in <a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a>.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0240" class="elsevierStylePara elsevierViewall">Meta-analysis results of FIT showed that the combined sensitivity for diagnosis was 76% for CRC (95% CI: 0.47–0.92), 25% for AA (95% CI: 0.14–0.39), and 55% for combined CRC and AA (95% CI: 0.29–0.77).</p><p id="par0245" class="elsevierStylePara elsevierViewall">The diagnostic odds ratio of the FIT test was 70.72 for CRC (95% CI: 17.04–293.54), 4.46 for AA (95% CI: 2.47–8.05) and 21.84 for combined CRC and AA (95% CI: 6.65–71.70). The results are presented in <a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5 and 6</a>.</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Reporting biases</span><p id="par0250" class="elsevierStylePara elsevierViewall">Deek's asymmetry test was used to assess publication bias across the studies.</p><p id="par0255" class="elsevierStylePara elsevierViewall">The statistically non-significant p-value for the slope coefficient suggests symmetry in the data and a low likelihood of publication bias across the studies regarding the diagnostic accuracy of Mt-sDNA testing for CRC (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.13) and AA (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.13) separately.</p><p id="par0260" class="elsevierStylePara elsevierViewall">There was a significant study bias across the studies on Mt-sDNA testing for combined CRC and AA (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03).</p><p id="par0265" class="elsevierStylePara elsevierViewall">Deek's asymmetry test was used to assess publication bias across the studies. There was a significant study bias across the studies on Mt-sDNA testing for combined CRC and AA (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03), but this was not significant for CRC (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.13) and AA (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.13) separately.</p><p id="par0270" class="elsevierStylePara elsevierViewall">The statistically non-significant p-value for the slope coefficient suggests symmetry in the data and a low likelihood of publication bias across the studies regarding the diagnostic accuracy of FIT tests for CRC (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.51), AA (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.67), and combined CRC and AA (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.36).</p><p id="par0275" class="elsevierStylePara elsevierViewall">The results with regression lines superimposed on a funnel plot are presented in Figs. 7 and 8.</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Certainly of evidences</span><p id="par0280" class="elsevierStylePara elsevierViewall">Heterogeneity analysis using the “midas” model showed that there was substantial heterogeneity between the 11 studies with Mt-sDNA results compared with colonoscopy, and the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> was 100 (95% CI: 100–100) for the CRC subgroup, <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>99 (95% CI: 98–99) for AA, and <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>100 (95% CI: 100–100) for the diagnosis of combined CRC and AA.</p><p id="par0285" class="elsevierStylePara elsevierViewall">Heterogeneity between the six studies with FIT tests and colonoscopy showed that <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>97 (95% CI: 95–99) for CRC diagnosis, <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>94 (95% CI: 90–99) for AA diagnosis, and <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> was 99 (95% CI: 99–100) for the diagnosis of combined CRC and AA.</p></span></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Discussion</span><p id="par0290" class="elsevierStylePara elsevierViewall">Meta-analyses of diagnostic accuracy studies of Mt-sDNA test showed a combined sensitivity of 89%, 51%, and 76% for the detection of CRC, AA, and combined CRC and AA, respectively. The overall specificity was 91%, 89%, and 90% for the detection of CRC, AA, and combined CRC and AA, respectively. Meta-analyses of diagnostic accuracy studies of the FIT test showed a combined sensitivity of 76%, 25% and 55% for the detection of CRC, AA, and combined CRC and AA, respectively. The combined specificity was 96%, 93%, and 95% for the detection of CRC, AA, and combined CRC and AA, respectively. Therefore, Mt-sDNA had a higher sensitivity for CRC and AA diagnosis, with almost the same specificity rates as FIT. The Mt-sDNA test is easy, safe, and convenient, does not require any dietary restrictions or bowel preparations, and should be performed every three years. However, using this test for CRC screening is still a challenge in terms of cost and accuracy.</p><p id="par0295" class="elsevierStylePara elsevierViewall">Despite reliable and comprehensive studies in the last two decades, additional evidence-based analysis is needed to prove the diagnostic accuracy and specificity of the multi-target stool DNA (Mt-sDNA) test. Therefore, this study aimed to collect and summarize test data during last 20 years, and conduct a meta-analysis, with respect to the Mt-sDNA test sensitivity and specificity, compared to colonoscopy.</p><p id="par0300" class="elsevierStylePara elsevierViewall">Colonoscopy is the most widely used and accepted CRC screening method in many countries, and is presented as the “gold standard” test due to being a sensitive and specific test. However, colonoscopy has some major barriers and limitations for implementation on a large scale in different populations.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> Stool-based screening modalities are patient-friendly, non-invasive, easy, quick, and can be performed at home by individuals. Historically, guaiac-based fecal occult blood test (gFOBT) was the most available and common test for CRC screening, but some of its disadvantages led to a decline in its popularity. Individuals must follow diet and drug restrictions and obtain three stool samples. Meanwhile, few evidence-based studies have revealed that the new stool based test and fecal immunochemical test (FIT) were significantly more sensitive and specific than other methods.<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">26–29</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">Recently, Mt-sDNA testing has emerged as a reliable, feasible, non-invasive, and patient-friendly modality for CRC screening, and has the potential to enhance screening and compliance. Previous screening modalities, including fecal occult blood, colonoscopy, and sigmoidoscopy, have side-affecting detection biases (right- or left-side), but the detection accuracy of the Mt-sDNA panel is unaffected by the site of cancer and/or adenoma.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> The diagnostic accuracy of Mt-sDNA test is increased and strengthened by improving the included targeted DNA alterations and hyper-methylations.</p><p id="par0310" class="elsevierStylePara elsevierViewall">The final established Mt-sDNA test panel, named “Cologuard” (Exact Sciences, Madison, WI, USA), was approved by the U.S. Food and Drug Administration (FDA) in August 2014 based on published results by Imperial et al. in 2014.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a> Cologuard was approved as a sensitive, non-invasive, and acceptable screening test for eligible average-risk individuals. Cologuard was included in the American Cancer Society's (2018) CRC screening guidelines and as a recommended option for adults over the age of 50 by the U.S. Preventive Services Task Force (2016) and the National Comprehensive Cancer Network (2016).</p><p id="par0315" class="elsevierStylePara elsevierViewall">Timeline of major milestones of Mt-sDNA test started by, Ahlquist et al., in 2000. They performed a feasibility study of an Mt-sDNA assay panel including point mutation detection of KRAS, p53, and Adenomatous polyposis coli (APC) genes, and a Microsatellite instability (MSI) assay of Bat-26. Their results showed that the Mt-sDNA panel had a sensitivity of 91% for CRC and 82% for AA, with a specificity of 93%. Meanwhile, they revealed that the Mt-sDNA assay could detect AA with a significantly higher sensitivity than the FIT (Hemoccult) test.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> Then in 2003, Tagore et al. designed and performed a large prospective study using the same stool DNA panel, supporting the feasibility of this test for CRC screening. However, the stool DNA panel was more sensitive to early stage lesions and AA in curable status compared to historical stool tests, including FOBT and/or FIT.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> The preliminary study report by Imperial et al. in 2004 revealed that although the diagnostic accuracy of Mt-sDNA is lower than that of colonoscopy for CRC, it had four times higher sensitivity and over two times higher sensitivity for invasive CRC and AA, respectively, compared to Hemoccult II.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> In 2012, Ahlquist et al., designed and incorporated the first clinical implementation of a novel Mt-sDNA panel assessed by a next-generation test. This novel prototype multi-marker panel included four gene methylation assays (NDRG4, BMP3, TFPI2, and vimentin), mutations in the K-ras gene, and ACTB (β-actin gene) as a reference gene, as well as FIT. The overall sensitivity for CRC detection was 85% and 63% for AA, with 90% specificity.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a></p><p id="par0320" class="elsevierStylePara elsevierViewall">The “DeeP-C” study started in middle of 2011 by Imperial et al., and their first results published in NEJM in 2014 (ClinicalTrials.gov identifier <a href="ctgov:NCT01397747">NCT01397747</a>). They compared the commercial FIT test with the new Mt-sDNA panel including quantitative molecular assays of K-ras mutation, methylation aberrations in the NDRG4 and BMP3 promoter regions, and β-actin, as well as the FIT test, among 9989 asymptomatic persons and 65 CRCs and 757 advanced precancerous lesions (APLs) were detected. This Mt-sDNA panel had significantly higher sensitivity for the detection of any CRC (92.3% vs. 73.8%) and advanced precancerous lesions (42.4% vs. 23.8%) compared with FIT alone. Although FIT was still more specific for both CRC and AA in this study, we know that sensitivity is the most important characteristic of any screening modality.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">Another major study provided better results using this Mt-sDNA panel in early 2016. Redwood et al. performed a prospective cross-sectional surveillance study among 661 asymptomatic Alaska Native adults (435 in the screening group and 226 in the surveillance group). Interestingly, their study revealed a sensitivity of 100% for CRC detection, and 75% for large adenomas in the screening group, with a specificity of 93%. Their results once again emphasized that Mt-sDNA has a significantly higher sensitivity for CRC and AA detection than FIT alone.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> However, Bosh et al., revealed lower CRC and AA detection rates among 6600 asymptomatic individuals in the Netherlands (Amsterdam and Rotterdam), with a sensitivity of 85.7% for CRC and 47.8% for AA; this study was performed between 2009 and 2010, before Food and Drug Administration (FDA) approval of Cologuard.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">In line with these studies, a few studies have tried to adjust the gene panel and modify the techniques used. For example, in 2017, Park et al., attempted to validate aberrantly hypermethylated promoter genes (SFRP2, TFPI2, NDRGA, and BMP3) as stool-based DNA markers for CRC and AA detection in the Korean population.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> Using these four markers, the sensitivity was lower than that of the Redwood trial (94.3% for CRC and 72.2% for AA) with a specificity of 55%. Thus, using only four methylated markers is not reliable enough for CRC screening compared with the Mt-sDNA panel,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> Sun et al., included the syndecan-2 protein (SDC2) and secreted frizzled-related protein 2 (SFRP2) methylation assessment in addition to the Cologuard panel for CRC screening in a Chinese population.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a> Next-generation sequencing analysis provided a larger and more comprehensive detection ability of most gene alterations and DNA methylation assays.</p><p id="par0335" class="elsevierStylePara elsevierViewall">The superior sensitivity of Mt-sDNA tests is still under fire because of its high cost and poor availability, and remains a challenge in deciding whether this screening strategy should be used at the population level. However US Preventative Services Task Force has been endorsed Mt-sDNA test as first-line CRC screening test, with about 70% adherence rate.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> Mt-sDNA test is cost effective compared with no screening, and is enough efficient compared with other screening modalities.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> Meanwhile, the cost effectiveness of Mt-sDNA test has been approved by a few microsimulation models compared to no screening, however Medicare beneficiaries study revealed acceptable cost-effectiveness threshold.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">12,33</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">While sessile serrated polyp (SSP) is a specific type of hyperplastic colonic polyp, and paly as a precursor of about 30% of all colorectal cancers, it is worth mentioning that we had limited evidence about including and detection of SSPs.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">34</span></a> Based on earlier research studies, FIT test was obviously undetectable for sessile serrated adenomas/polyps, while MT-sDNA had larger diagnostic accuracy.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> Also the analytic results of Bosch et al, revealed that advanced serrated polyp(ASP) detection by MT-sDNA test was significantly superior to that by FIT, with higher sensitivity (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02), as the sensitivity was 40.7%(95% CI: 22.4–61.2) for MT-sDNA compared with sensitivity of 7.4%(95% CI: 0.9–24.3) for FIT test including 3 threshold (50, 75, and 100).<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a> Also Redwood et al study showed the detection accuracy of 67% by MT-sDNA vs 11% by FIT (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.07) for sessile serrated polyps.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> Despite the superior diagnostic accuracy of MT-sDNA panel for SSPs, and regarding the importance of these types of polyps as precancerous lesion, we just find only 4 relevant studies, that reported data for serrated lesions, so due to lack of data, we didn’t included this option as our aims and in analysis.</p><p id="par0345" class="elsevierStylePara elsevierViewall">The reluctance to switch from FIT to Mt-sDNA test for screening programs is the high cost of Mt-sDNA test resulting in lower overall cost-effectiveness and availability of this test compared to FIT or colonoscopy. Despite the approved advantages of Mt-sDNA test, more evidences need to focus more on the barriers to the widespread use of Mt-sDNA in screening programs.</p><p id="par0350" class="elsevierStylePara elsevierViewall">However, ensuring the clinical diagnostic accuracy of the Mt-sDNA test for any CRC and precancerous lesions is still one of the main concerns of health care providers.</p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Limitations</span><p id="par0355" class="elsevierStylePara elsevierViewall">As the Mt-sDNA test has been recently approved by the FDA for routine use in CRC screening, we found limited studies about the accuracy of this test. Although molecular tests and techniques have been developed over the last two decades, there is a discrepancy in the results of sensitivity and specificity of this test, largely due to study sample size and included gene alterations and DNA methylation tests. Therefore, there was a significant study bias across studies regarding the diagnostic accuracy of Mt-sDNA testing for CRC and AA. However the studies included some kind of multitarget testing in stool, but with different markers. Also some recent trials included additional target tests and updated the “Cologuard” panel, for achieving better accuracy results. Then, the pooled performance is not referred only to Cologuard, but the combination of many studies.</p></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Conclusions</span><p id="par0360" class="elsevierStylePara elsevierViewall">The superior sensitivity of Mt-sDNA tests is still under fire because of its high cost and poor availability, and it is still unclear how test results could be verified independently by other tests. However, our study results show that Mt-sDNA assays have a higher sensitivity for CRC and AA diagnosis. Mt-sDNA tests have major advantages over previously commonly used stool based tests (gFOBT and FIT) in average-risk populations. This evidence indicates the reliability and accuracy of Mt-sDNA tests in population-based CRC screening programs. However, larger population-based screening studies and clinical trials using the Mt-sDNA tests are needed in the future.</p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Authors’ contributions</span><p id="par0365" class="elsevierStylePara elsevierViewall">RD, SD, MAJ: Performed substantial contributions to the conception and design of the work; the acquisition, analysis, and interpretation of data for the work; AND HMA, MHS: Performed drafting the work and revising it critically for important intellectual content; AND MHS: Revised and approved the version to be published; AND All the authors confirmed agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.</p></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Availability of data and material</span><p id="par0370" class="elsevierStylePara elsevierViewall">Data are openly available in a public repository that issues datasets with the responsibility of the corresponding author.</p></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Statement of ethics</span><p id="par0375" class="elsevierStylePara elsevierViewall">Current study was reviewed and corroborated by the ethics committee of Tabriz University of Medical Sciences (ID: IR.TBZMED.REC.1395.1333).</p></span><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Consent to participants</span><p id="par0380" class="elsevierStylePara elsevierViewall">N/A.</p></span><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Consent for publication</span><p id="par0385" class="elsevierStylePara elsevierViewall">The manuscript has been read and approved by all the authors, that the requirements for authorship as stated earlier in this document have been met, and that each author believes that the manuscript represents honest work, if that information is not provided in another form. All authors accepted the consent for publication.</p></span><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Funding</span><p id="par0390" class="elsevierStylePara elsevierViewall">The study was approved and supported as a research grant, by <span class="elsevierStyleGrantSponsor" id="gs1">Ministry of Health and Medical Education, Deputy of Research and Technology</span> (Grant number: <span class="elsevierStyleGrantNumber" refid="gs1">700/98</span>, 2015.03.14 [1394/12/24]) from Iran Ministry of Health.</p></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Conflicts of interest</span><p id="par0395" class="elsevierStylePara elsevierViewall">The author reports no conflicts of interest in this work.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:20 [ 0 => array:3 [ "identificador" => "xres1805292" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1577746" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1805291" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1577745" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:11 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Eligibility criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Information sources" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Search strategy" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Selection process" ] 4 => array:3 [ "identificador" => "sec0035" "titulo" => "PICOS" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Participants" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Intervention" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Control/compare" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Outcome" ] 4 => array:3 [ "identificador" => "sec0060" "titulo" => "Setting" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Clinical validity" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Publication date" ] ] ] ] ] 5 => array:2 [ "identificador" => "sec0075" "titulo" => "Data collection process" ] 6 => array:2 [ "identificador" => "sec0080" "titulo" => "Data items" ] 7 => array:2 [ "identificador" => "sec0085" "titulo" => "Study risk of bias assessment" ] 8 => array:2 [ "identificador" => "sec0090" "titulo" => "Effect measures" ] 9 => array:2 [ "identificador" => "sec0095" "titulo" => "Synthesis methods" ] 10 => array:2 [ "identificador" => "sec0100" "titulo" => "Reporting bias assessment" ] ] ] 6 => array:3 [ "identificador" => "sec0105" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0110" "titulo" => "Study selection" ] 1 => array:2 [ "identificador" => "sec0115" "titulo" => "Study characteristics" ] 2 => array:2 [ "identificador" => "sec0120" "titulo" => "Risk of bias in studies" ] 3 => array:2 [ "identificador" => "sec0125" "titulo" => "Results of individual studies" ] 4 => array:2 [ "identificador" => "sec0130" "titulo" => "Mt-sDNA test subgroup" ] 5 => array:2 [ "identificador" => "sec0135" "titulo" => "FIT test subgroup" ] ] ] 7 => array:3 [ "identificador" => "sec0140" "titulo" => "Results of synthesis" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0145" "titulo" => "Reporting biases" ] 1 => array:2 [ "identificador" => "sec0150" "titulo" => "Certainly of evidences" ] ] ] 8 => array:2 [ "identificador" => "sec0155" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0160" "titulo" => "Limitations" ] 10 => array:2 [ "identificador" => "sec0165" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0170" "titulo" => "Authors’ contributions" ] 12 => array:2 [ "identificador" => "sec0175" "titulo" => "Availability of data and material" ] 13 => array:2 [ "identificador" => "sec0180" "titulo" => "Statement of ethics" ] 14 => array:2 [ "identificador" => "sec0185" "titulo" => "Consent to participants" ] 15 => array:2 [ "identificador" => "sec0190" "titulo" => "Consent for publication" ] 16 => array:2 [ "identificador" => "sec0195" "titulo" => "Funding" ] 17 => array:2 [ "identificador" => "sec0200" "titulo" => "Conflicts of interest" ] 18 => array:2 [ "identificador" => "xack637033" "titulo" => "Acknowledgments" ] 19 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-11-27" "fechaAceptado" => "2022-01-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1577746" "palabras" => array:5 [ 0 => "Colorectal cancer" 1 => "Screening" 2 => "Accuracy" 3 => "Multitarget" 4 => "Stool test" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1577745" "palabras" => array:5 [ 0 => "Cáncer colorrectal" 1 => "Poner en pantalla" 2 => "Exactitud" 3 => "Multiobjetivo" 4 => "Prueba de heces" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This study aimed to collect and summarize test data and conduct a meta-analysis, with respect to the Multitarget Stool DNA test sensitivity and specificity, compared to colonoscopy.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">All manuscripts were screened for eligibility according to inclusion criteria. Participants were a normal population at an average risk of developing CRC. Intervention was Stool based and DNA panel tests compared with colonoscopy, and outcome was detection of CRC and any pre-cancerous lesions. Inter-study and inconsistency (using the <span class="elsevierStyleItalic">I</span>-squared test) were assessed.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Meta-analyses of the Mt-sDNA test showed a combined sensitivity of 89%, 51%, and 76% for the detection of CRC, advanced adenoma (AA), and combined CRC and AA, respectively. The overall specificity was 91%, 89%, and 90% for the detection of CRC, AA, and combined CRC and AA, respectively.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Mt-sDNA had significantly acceptable diagnostic accuracy for CRC and AA diagnosis, but still has lower sensitivity and specificity than colonoscopy.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Este estudio tuvo como objetivo recopilar y resumir los datos de las pruebas y realizar un metaanálisis con respecto a la sensibilidad y especificidad de la prueba de DNA en heces multiobjetivo, en comparación con la colonoscopia.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Todos los manuscritos fueron examinados para determinar su elegibilidad de acuerdo con los criterios de inclusión. Los participantes eran una población normal con un riesgo promedio de desarrollar CRC. La intervención se basó en heces y pruebas de panel de DNA en comparación con la colonoscopia, y el resultado fue la detección de CRC y cualquier lesión precancerosa. Se evaluaron la inconsistencia entre estudios y la inconsistencia (mediante la prueba de I cuadrado).</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los metaanálisis de la prueba Mt-sDNA mostraron una sensibilidad combinada del 89%, 51% y 76% para la detección de CRC, adenoma avanzado (AA) y CRC y AA combinados, respectivamente. La especificidad general fue del 91%, 89% y 90% para la detección de CRC, AA y CRC y AA combinados, respectivamente.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Mt-sDNA tuvo una precisión diagnóstica significativamente aceptable para el diagnóstico de CRC y AA, pero aún tiene una sensibilidad y especificidad más bajas que la colonoscopia.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusión" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0410" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0210" ] ] ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2503 "Ancho" => 2500 "Tamanyo" => 315570 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">PRISMA flow diagram of study protocols.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1294 "Ancho" => 2917 "Tamanyo" => 206680 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Summary receiver operating characteristic plot (SROC), of the Mt-SDNA test screening tests diagnostic accuracy for: (A) cancer, (B) advanced adenoma, (C) combined CRC and AA detection, graphical summaries of the fitted model.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:2 [ 0 => array:1 [ "imagen" => "gr3ab.jpeg" ] 1 => array:1 [ "imagen" => "gr3c.jpeg" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Paired forest plot of sensitivity and specificity of Mt-SDNA test for detection of: (A) cancer, (B) advanced adenoma, (C) combined CRC and AA.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1297 "Ancho" => 2917 "Tamanyo" => 215593 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Summary receiver operating characteristic plot of the FIT test screening tests diagnostic accuracy for: (A) cancer, (B) advanced adenoma, (C) combined CRC and AA detection.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:2 [ 0 => array:1 [ "imagen" => "gr5a.jpeg" ] 1 => array:1 [ "imagen" => "gr5b.jpeg" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Paired Forest plot of sensitivity and specificity of FIT test for detection of: (A) cancer, (B) advanced adenoma, (C) combined CRC and AA.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author/country (refs) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study type/design \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of case/control in each group \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AgeMedian/mean (range) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervention tests \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Length of follow-up \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mu J et al., 2020China<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blinded case control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 839</span><span class="elsevierStyleUnderline">Case: 252</span>CRC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>203Advanced colorectal neoplasia<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>49<span class="elsevierStyleUnderline">Control: 587</span>Non-advanced neoplasia<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>156Normal Subjects<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>431 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40–85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-BMP3-NDRG4-β actin- methylated B2M quantitation<span class="elsevierStyleUnderline">“ColoClear” similar to ColoGuard and FIT (Hemmocult II)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1st May 2015 to 30th October 2017 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bosch LJW et al., 2019Netherlands<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Randomized control trial (screening) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated</span> 1014- CRC: 7- Advanced precancerous lesions: 119- Advanced Adenoma: 92- Advanced Serrated Polyp: 27- High-grade Dysplasia: 22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50–75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-BMP3-NDRG4-β actin<span class="elsevierStyleUnderline">and FIT (OC-Sensor; Eiken Chemical,Tokyo, Japan)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From June 2009 and July 2010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sun M et al., 2019China<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case–control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 233</span><span class="elsevierStyleUnderline">Cases</span>:CRC: 105AA: 20Polyps: 6<span class="elsevierStyleUnderline">Controls</span>:102 (Colonoscopy negative) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not assessed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-BMP3-NDRG4-SDC2-SFRP2<span class="elsevierStyleUnderline">and FIT(Fecal Occult Blood Test Kit (colloidal gold)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not assessed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Park SK et al., 2017Korea<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Randomized control trial (screening) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 111</span>- CRC: 35- AA: 36- Normal: 40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean: 55.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Stool-based DNA methylation markers</span>:-SFRP2-TFPI2-NDRG4-BMP3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Between August 2012 and March 2014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Redwood DG et al., 2016Alaska<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prospective, cross-sectional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 661</span><span class="elsevierStyleUnderline">Screening Relevant Colorectal Neoplasia (SRN): 92</span>CRC: 10Villous Adenoma: 28Sessile serrated polyps ≥1<span class="elsevierStyleHsp" style=""></span>cm: 16Tubular adenoma: 38<span class="elsevierStyleUnderline">Non-SRN: 569</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40–85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-BMP3-NDRG4-β actin(Cologuard)<span class="elsevierStyleUnderline">and FIT (OCSensor Diana, PolyMedco, Inc, Portlandt, NY)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From February 6, 2012, through August 7, 2014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imperial TF et al., 2014USA<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross sectional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 9989</span>CRC: 65Advanced precancerous lesions: 757High Grade dysplasia: 39Sessile serrated polyps ≥1<span class="elsevierStyleHsp" style=""></span>cm: 99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50–84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-BMP3-NDRG4-β actin(Cologuard)<span class="elsevierStyleUnderline">and FIT(OC FIT-CHEK, Polymedco)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From June 2011 to November 2012 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lidgard GP et al., 2013USA<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blinded, multicenter, case–control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 1003</span> (459 asymptomatic patients and 544 referred patients)CRC: 93Advanced Adenoma: 84Sessile Serrated Adenoma ≥1<span class="elsevierStyleHsp" style=""></span>cm: 30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median 65 years (range 38–87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-BMP3-NDRG4-β actin<span class="elsevierStyleUnderline">and FIT(OC-FIT CHEK, Polymedco, Cortlandt Manor, NY)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not assessed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ahlquist DA et al., 2012USA, Canada, Denmark<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blinded multicenter case–control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 678</span><span class="elsevierStyleUnderline">Cases:385</span>252 CRC, 133 adenoma<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleUnderline">Controls: 293</span> (normal colonoscopy) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 (39–92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-NDRG4-BMP3-TFPI2-Vimentin-β-actinHemoglobin (HemoQuant) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not assessed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imperial TF et al., 2004USA<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Randomized control trial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 4404</span>CRC: 31CRC plus adenomas with High grade dysplasia: 71Advanced adenoma: 403Minor polyp: 648Normal: 1423 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥50 (68.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-APC-P53-BAT-26-Long DNA<span class="elsevierStyleUnderline">Hemoccult II (guaiac-based tests)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">From August 2001 and March 2003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tagore KS et al., 2003USA<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Case control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 212</span><span class="elsevierStyleUnderline">Cases: 80</span>52 invasive CRC, 28 advanced adenoma<span class="elsevierStyleUnderline">Controls: 212</span>113: Negative colonoscopy99: minor polyps \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-MTAP-KRAS-P53-APC-BAT-26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">not assessed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ahlquist DA et al., 2000USA<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Feasibility StudyIncluding 2 clinical pilot clinical trials \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Total evaluated 61</span>CRC: 22Adenoma<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>cm: 11Normal: 28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median 70 (38–88) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Multitarget stool DNA panel</span>:-KRAS-APC-P53-Bat-26-L-DNA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not assessed \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Summary information of 11 included studies in systematic review and meta-analysis.</p>" ] ] 6 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Recommended testing interval \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sensitivity<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a></th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Specificity<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Procedure \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Harms \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Cost \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Availability \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Diet and/or medication restriction \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Patient compliance rate \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Side-affecting detection biases \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Colorectal cancer \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Advanced adenoma \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MT-sDNA test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Every 3 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24–42% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Simple \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-invasive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Costly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Less available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nearly 70% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unaffected \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FIT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Annually \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76–95% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27–47% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89–96% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Simple \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-invasive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">More cost-effective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">More available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nearly 14% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Affected \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Comparing multitarget stool DNA and FIT tests, advantages and disadvantages.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">6,35</span></a>.</p>" ] ] 7 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.doc" "ficheroTamanyo" => 71064 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib0180" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. 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| 2024 November | 1 | 1 | 2 |
| 2024 October | 4 | 4 | 8 |
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| 2024 July | 1 | 0 | 1 |
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| 2024 March | 10 | 9 | 19 |
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| 2024 January | 7 | 0 | 7 |
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| 2023 June | 14 | 2 | 16 |
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| 2023 March | 10 | 5 | 15 |
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| 2022 December | 21 | 11 | 32 |
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| 2022 September | 0 | 2 | 2 |
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