Sensitivity of second-generation blood-based methylated Septin9 assay for early-stage colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 419-419 ◽  
Author(s):  
Gunter Weiss ◽  
Anne Fassbender ◽  
Thomas Koenig ◽  
Reimo Tetzner
Keyword(s):  
Colorectal Cancer ◽  
Real Time ◽  
Real Time Pcr ◽  
Early Stage ◽  
Screening Colonoscopy ◽  
Molecular Diagnostic ◽  
Control Group ◽  
Average Risk ◽  
Early Stage Disease ◽  
Crc Screening

419 Background: Early detection of colorectal cancer (CRC) has been shown to decrease mortality, although compliance to CRC screening is low. Availability of a blood-based test is expected to improve CRC screening compliance. Specific detection of CRC using the Septin9 biomarker (mSEPT9) in a large prospective trial of an average-risk CRC screening population exhibited 67% sensitivity for CRC with 88% specificity. Laboratory-developed tests detecting mSEPT9 in plasma are now available in North America and a 2nd generation molecular diagnostic blood test for mSEPT9 is available as a CE-marked kit in Europe. The current research evaluated the clinical performance of the 2nd generation mSEPT9 assay. Methods: Bisulfite-converted DNA (bisDNA) was prepared from 3.5 mL human plasma using the 2ndgeneration plasma DNA preparation kit. Resulting bisDNA was analyzed in triplicate on the ABI7500 Fast Dx (Life Technologies, Inc.) using proprietary HeavyMethyl real-time PCR technology for mSEPT9 and the 2nd generation real-time PCR kit. In a case – control design, plasma from 98 CRC patients (n = 87 stages I - III) and 99 age-matched, colonoscopy-verified normal individuals were processed with the mSEPT9 assay. In addition, plasma from 150 prospectively enrolled average risk individuals scheduled for screening colonoscopy was tested. mSEPT9 was qualitatively analyzed such that any detection of mSEPT9 in a PCR was called “positive”. Results: The revised mSEPT9 assay exhibited 95% sensitivity (95% CI: 89-98%) for CRC. Sensitivity for stage I was 89% (95% CI: 72-96%, n = 27) and sensitivity for stage II was 93% (95% CI: 78-98%, n = 29). The control group was positive at a rate of 16% (95% CI: 10-25%). Specificity of the mSEPT9 assay in the screening cohort was 85% (95% CI: 78-89%). Conclusions: The 2nd generation mSEPT9 assay demonstrated improved sensitivity for CRC without significant impact on specificity. The enhanced design and robustness of the assay will further facilitate its standardized use in routine laboratory settings. Finally, the increased sensitivity of the revised mSEPT9 assay improves the detection of early stage disease and demonstrates the feasibility of a blood-based CRC screening technology.

scholarly journals Unintended Consequences of Health Information Technology: Evidence From Veterans Affairs Colorectal Cancer Oncology Watch Intervention

2012 ◽  
Vol 30 (32) ◽  
pp. 3947-3952 ◽  
Author(s):  
John Bian ◽  
Charles L. Bennett ◽  
Deborah A. Fisher ◽  
Maria Ribeiro ◽  
Joseph Lipscomb
Keyword(s):  
Colorectal Cancer ◽  
Fixed Effects ◽  
Veterans Affairs ◽  
Unintended Consequences ◽  
Screening Colonoscopy ◽  
Average Risk ◽  
Cross Sectional ◽  
Risk Screening ◽  
Crc Screening ◽  
Clinical Reminder

Purpose We evaluated the Colorectal Cancer (CRC) Oncology Watch intervention, a clinical reminder implemented in Veterans Integrated Service Network 7 (including eight hospitals) to improve CRC screening rates in 2008. Patients and Methods Veterans Affairs (VA) administrative data were used to construct four cross-sectional groups of veterans at average risk, age 50 to 64 years; one group was created for each of the following years: 2006, 2007, 2009, and 2010. We applied hospital fixed effects for estimation, using a difference-in-differences model in which the eight hospitals served as the intervention sites, and the other 121 hospitals served as controls, with 2006 to 2007 as the preintervention period and 2009 to 2010 as the postintervention period. Results The sample included 4,352,082 veteran-years in the 4 years. The adherence rates were 37.6%, 31.6%, 34.4%, and 33.2% in the intervention sites in 2006, 2007, 2009, and 2010, respectively, and the corresponding rates in the controls were 31.0%, 30.3%, 32.3%, and 30.9%. Regression analysis showed that among those eligible for screening, the intervention was associated with a 2.2–percentage point decrease in likelihood of adherence (P < .001). Additional analyses showed that the intervention was associated with a 5.6–percentage point decrease in likelihood of screening colonoscopy among the adherent, but with increased total colonoscopies (all indicators) of 3.6 per 100 veterans age 50 to 64 years. Conclusion The intervention had little impact on CRC screening rates for the studied population. This absence of favorable impact may have been caused by an unintentional shift of limited VA colonoscopy capacity from average-risk screening to higher-risk screening and to CRC surveillance, or by physician fatigue resulting from the large number of clinical reminders implemented in the VA.

scholarly journals Colorectal Cancer Screening: Video-Reviewed Flexible Sigmoidoscopy by Nurse Endoscopists — A Canadian Community-Based Perspective

2001 ◽  
Vol 15 (7) ◽  
pp. 441-445 ◽  
Author(s):  
TF Shapero ◽  
PE Alexander ◽  
J Hoover ◽  
E Burgis ◽  
R Schabas
Keyword(s):  
Colorectal Cancer ◽  
Flexible Sigmoidoscopy ◽  
Screening Program ◽  
Early Stage ◽  
Community Setting ◽  
Average Risk ◽  
Crc Screening ◽  
Asymptomatic Patients ◽  
Incident Cancer

BACKGROUND: Colorectal cancer (CRC) is the third most common incident cancer and the second most fatal cancer in Canada. Flexible sigmoidoscopy (FS) is one of the modalities under consideration for CRC screening. The present series reports on a screening program of FS performed by nonphysician endoscopists in a Canadian community setting, with video review of procedures by physicians and recommendation of follow-up colonoscopy where polyps are identified.RESULTS: Five hundred twenty-five, average-risk, asymptomatic patients were examined. After exclusion of inappropriate referrals, 488 remained for analysis. The duration and extent of examination were comparable with those of previous studies elsewhere. Compliance with suggested follow-up was 97.3%. Polyps were identified at FS in 15.4% of examinees. In 8.2% of patients, the polyps were neoplastic at subsequent histology. Four malignant lesions were detected, all at an early stage. There were no complications of FS.INTERPRETATION: This report shows that FS can be carried out safely and effectively by nonphysician personnel in a community setting in Canada. The manpower cost for nonphysician operators is considerably less than that for specialist physician endoscopists. This approach deserves consideration in cost effectiveness analyses of CRC screening.

scholarly journals Directly Mailing gFOBT Kits to Previous Responders Being Recalled for Colorectal Cancer Screening Increases Participation

2019 ◽  
Vol 3 (5) ◽  
pp. 197-203
Author(s):  
Jill Tinmouth ◽  
Jigisha Patel ◽  
Peter C Austin ◽  
Nancy N Baxter ◽  
Melissa C Brouwers ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Primary Care ◽  
Care Provider ◽  
Primary Care Provider ◽  
Intervention Group ◽  
Absolute Difference ◽  
Control Group ◽  
Fecal Occult Blood ◽  
Average Risk ◽  
Crc Screening

Abstract Background Colorectal cancer (CRC) screening with guaiac fecal occult blood test (gFOBT) reduces CRC-related death. Average risk individuals should be recalled for screening with gFOBT every 2 years in order to maximize effectiveness. However, adherence with repeated testing is often suboptimal. Our aim was to evaluate whether adding a gFOBT kit to a mailed recall letter improves participation compared with a mailed recall letter alone, among previous responders to a mailed invitation. Methods We conducted a cluster randomized controlled trial, with the primary care provider as the unit of randomization. Eligible patients had completed a gFOBT and tested negative in an earlier pilot study and were now due for recall. The intervention group received a mailed CRC screening recall letter from their primary care provider plus a gFOBT kit (n = 431) while the control group received a mailed CRC screening mailed recall letter alone (n = 452). The primary outcome was the uptake of gFOBT or colonoscopy within 6 months. Results gFOBT uptake was higher in the intervention group (61.3%, n = 264) compared with the control group (50.4%, n = 228) with an absolute difference between the two groups of 10.8% (95% confidence interval [CI]: 1.4 to 20.2%, P = &lt;0.01). Patients in the intervention group were more likely to complete the gFOBT compared with the control group (odds ratio [OR] = 1.4; 95% CI: 1.1 to 1.9). Conclusion Our findings show that adding gFOBT kits to the mailed recall letter increased participation among persons recalled for screening. Nine gFOBT kits would have to be sent by mail in order to screen one additional person.

scholarly journals Effects of Screening for Colorectal Cancer: Development and Validation of a Multistate Markov Model

2020 ◽  
Author(s):  
Thomas Heisser ◽  
Michael Hoffmeister ◽  
Hermann Brenner
Keyword(s):  
Colorectal Cancer ◽  
Markov Model ◽  
Time Course ◽  
Intervention Group ◽  
Medical Decision ◽  
Screening Colonoscopy ◽  
Control Group ◽  
German Population ◽  
Crc Screening ◽  
Incidence And Mortality

AbstractSimulation models are a powerful tool to overcome gaps of evidence needed to inform medical decision making. Here, we present development and application of a multistate Markov model to simulate effects of colorectal cancer (CRC) screening, along with a thorough assessment of the model’s ability to reproduce real-life outcomes. Firstly, we provide a comprehensive documentation of the model development, structure and assumptions. Secondly, to assess the model’s external validity, we compared model-derived cumulative incidence and prevalences of colorectal neoplasms to (1) results from KolosSal, a study in German screening colonoscopy participants, (2) registry-based estimates of CRC incidence in Germany, and (3) outcome patterns of randomized sigmoidoscopy screening studies. We found that (1) more than 90% of model-predicted neoplasm prevalences were within the 95% confidence intervals of the observed prevalences in the KolosSal study; (2) the 15-year cumulative CRC incidences estimated by simulations for the German population deviated by 0.0-0.2 percent units in men and 0.0-0.3 percent units in women when compared to corresponding registry-derived estimates; and (3) the time course of cumulative CRC incidence and mortality in the modelled intervention group and control group closely resembles the time course reported from sigmoidoscopy screening trials. Summarized, our model adequately predicted colorectal neoplasm prevalences and incidences in a German population for up to 25 years, with estimated patterns of the effect of screening colonoscopy resembling those seen in registry data and real-world studies. This suggests that the model represents a valid tool to assess the comparative effectiveness of strategies for CRC screening.

Colorectal Cancer Screening

2021 ◽  
pp. 53-60
Author(s):  
Caitlin C. Murphy ◽  
Sally W. Vernon
Keyword(s):  
Colorectal Cancer ◽  
Patient Navigation ◽  
The United States ◽  
Professional Organizations ◽  
Screening Colonoscopy ◽  
Average Risk ◽  
National Goal ◽  
Absolute Increase ◽  
Crc Screening ◽  
Multicomponent Interventions

Colorectal cancer (CRC) screening is endorsed as an effective preventive health service because it reduces morbidity and mortality from CRC. Regular screening with stool blood tests or sigmoidoscopy facilitates earlier detection of CRC and lowers mortality; screening colonoscopy may also decrease CRC incidence through early detection and removal of precancerous polyps. Most professional organizations recommend that screening begin at age 50 years for those at average risk, and in the United States, about 60% of age-eligible adults are up-to-date with screening. Importantly, prevalence of CRC screening differs by race/ethnicity, educational attainment, and insurance status, with marked disparities in screening among racial/ethnicity minorities and the uninsured. Recent CRC screening interventions have focused on mailed outreach, patient navigation, and offering a choice of screening test, and many studies have been conducted in large, integrated healthcare systems or federally qualified health centers. In these settings, mailed outreach and patient navigation, particularly in the context of multicomponent interventions, increased CRC screening (e.g., absolute increase of 28% across trials of mailed outreach). Moving forward, CRC screening interventions must include more than one-time screening and involve a series of coordinated steps, from initial screening to diagnostic evaluation to treatment of any detected lesions. Patient navigation and mailed outreach have been the most extensively tested interventions for increasing screening. Patient navigation appears to have a similar impact on follow-up of abnormal test results. Broad implementation of either of these strategies may bring the current screening prevalence of 60% closer to the national goal of 80%.

RPS24c Isoform Facilitates Tumor Angiogenesis Via Promoting the Stability of MVIH in Colorectal Cancer

2020 ◽  
Vol 20 (5) ◽  
pp. 388-395 ◽  
Author(s):  
Yue Wang ◽  
Youjun Wu ◽  
Kun Xiao ◽  
Yingjie Zhao ◽  
Gang Lv ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ribosomal Protein ◽  
Real Time ◽  
Tumor Angiogenesis ◽  
Real Time Pcr ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Binding Interaction ◽  
Tubule Formation ◽  
The Stability

Background: Colorectal cancer (CRC) is the second leading cause of death worldwide, and distant metastasis is responsible for the poor prognosis in patients with advanced-stage CRC. RPS24 (ribosomal protein S24) as a ribosomal protein, multiple transcript variant encoding different isoforms have been found for this gene. Our previous studies have demonstrated that RPS24 is overexpressed in CRC. However, the mechanisms underlying the role of RPS24 in tumor development have not been fully defined. Methods: Expression of RPS24 isoforms and lncRNA MVIH in CRC tissues and cell lines were quantified by real-time PCR or western blotting assay. Endothelial tube formation assay was performed to determine the effect of RPS24 on tumor angiogenesis. The cell viability of HUVEC was determined by MTT assay, and the migration and invasion ability of HUVEC were detected by transwell assay. PGK1 secretion was tested with a specific ELISA kit. Results: Here, we found that RPS24c isoform was a major contributor to tumor angiogenesis, a vital process in tumor growth and metastasis. Real-time PCR revealed that RPS24c isoform was highly expressed in CRC tissues, while other isoforms are present in both normal and CRC tissues with no statistical difference. Moreover the change of RPS24 protein level is mainly due to the fluctuation of RPS24c. Furthermore, we observed that silencing RPS24c could decrease angiogenesis by inhibiting tubule formation, HUVEC cell proliferation and migration. Additionally, we investigated the molecular mechanisms and demonstrated that RPS24c mRNA interacted with lncRNA MVIH, the binding-interaction enhanced the stability of each other, thereby activated angiogenesis by inhibiting the secretion of PGK1. Conclusion: RPS24c facilitates tumor angiogenesis via the RPS24c/MVIH/PGK1 pathway in CRC. RPS24c inhibition may be a novel option for anti-vascular treatment in CRC.

scholarly journals Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chang Woo Kim ◽  
Hyunjin Kim ◽  
Hyoung Rae Kim ◽  
Bong-Hyeon Kye ◽  
Hyung Jin Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Early Detection ◽  
Prospective Trial ◽  
Screening Colonoscopy ◽  
Quantitative Detection ◽  
Screening Programs ◽  
Crc Screening ◽  
Stool Dna ◽  
Dna 2

Abstract Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1.

scholarly journals Cross-sectional adherence with the multi-target stool DNA test for colorectal cancer screening in a large, nationally insured cohort

2021 ◽  
Author(s):  
Lesley-Ann Miller-Wilson ◽  
Lila J Finney Rutten ◽  
Jack Van Thomme ◽  
A Burak Ozbay ◽  
Paul J Limburg
Keyword(s):  
Colorectal Cancer ◽  
National Sample ◽  
Adherence Rate ◽  
Average Risk ◽  
Cross Sectional ◽  
Commercial Insurance ◽  
Dna Test ◽  
Crc Screening ◽  
Stool Dna ◽  
Insured Patients

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

scholarly journals The association of male infertility with telomere length: A case control study

2021 ◽  
Vol 8 (4) ◽  
pp. 325-332
Author(s):  
Kate Deepali Rajesh ◽  
Puranam Vatsalaswamy ◽  
Manvikar Purshotam Rao
Keyword(s):  
Male Infertility ◽  
Telomere Length ◽  
Real Time ◽  
Real Time Pcr ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Significant Difference ◽  
Control Study ◽  
Sperm Telomere Length

To study the relevance of sperm telomere length and infertility in men. : Our case-control study included twenty-five males in couple with sub-fertility/infertility (test group) and twenty five healthy males (control group) with proven paternity in the age group 25 to 35 years. The Absolute Sperm Telomere length (aSTL) was measured by real-time PCR. We investigated whether any significant difference in the aSTL value existed between the groups and analysed the relationship between aSTL and other sperm parameters.The mean (SE) aSTL recorded in the infertile cases was significantly shorter than for the control group being 140.60 (6.66) Kb/genome and 239.63 (12.32) Kb/genome respectively (p &#60;0.001) A weak correlation was eminent between aSTL kb/genome and the total sperm count mil/ml (rho= 0.04, p - 0.86), progressive sperm motility (rho= - 0.02, p=0.934) and sperm viability (rho= - 0.07 p=0.741) in the infertile group. The measurement of aSTL by real-time PCR is a simple and rapid method that offers further paramount information with respective to the quality of sperm. It is befitted for epidemiological studies, hence opening new perspectives in the evaluation of male infertility. Limitations - Our study was confined to men aged between 25 and 35 years. Further comparative studies are needed to explore the significance of STL and infertility in older males. Additional studies will help illumine the significance of aSTL as a prognostic biomarker in assisted reproduction.

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