Analytical and clinical validation of the TruCheck platform for diagnostic triaging of symptomatic cases suspected of colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 24-24
Author(s):  
Dadasaheb B Akolkar ◽  
Darshana Patil ◽  
Pradip Fulmali ◽  
Pooja Fulmali ◽  
Revati Patil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Limit Of Detection ◽  
Significant Proportion ◽  
Clinical Validation ◽  
Analytical Validation ◽  
Invasive Approach ◽  
Blood Samples ◽  
Non Invasive ◽  
Asymptomatic Individuals ◽  
Sensitivity Specificity

24 Background: Trucheck is a non-invasive approach for diagnostic triaging of symptomatic individuals who are suspected of Colorectal Cancer (CRC) and have been advised an invasive biopsy. Trucheck evaluates blood samples for presence of Circulating Ensembles of Tumor Associated Cells (C-ETACs: EpCAM+, Pan-CK+, CD45±) originating from a primary Colorectal Adenocarcinoma (CR-AD: CDX-2, CK-20, Muc2); such C-ETACs are unexpected in asymptomatic individuals as well as in individuals with benign Colorectal conditions. Methods: For Analytical Validation, spike-recovery analysis was performed using control cells / cell lines for EpCAM (SKBR-3), Pan-CK (SKBR-3), CD45 (PBMCs), CDX2 (CaCO2), CK20 (HCT15) and MUC2 (SW620) to determine the Sensitivity, Specificity, Accuracy, Limit of Detection, Linearity and Precision. Clinical Validations were performed using 15 mL blood samples from 587 participants. An initial Retrospective Clinical Pre-validation was based on blood samples from 350 known cases of CR-AD and 20 cases of non-CRC. The Prospective Clinical Validation was performed on blood samples collected prior to any invasive procedures from 217 symptomatic cases suspected of CRC. Results: Analytical Validation indicated 100% Sensitivity, 100% Specificity, 100% Accuracy, 90% Precision and significant linearity (R2≥0.98) for all ICC markers. Clinical Pre-validation indicated 84.9 % Sensitivity and 100% Specificity for CR-AD v/s non-CRC. In the Prospective Clinical Validation cohort, histopathological evaluation (HPE) of biopsied tumor tissue indicated benign Colorectal conditions in 10 cases and CR-AD 207 of the 217 suspected cases. Based on HPE as the standard, the Trucheck approach had 90.3% Sensitivity, 100% Specificity and 95.2% Accuracy. Conclusions: Symptomatic individuals suspected of CRC may benefit from the sensitive and specific non-invasive Trucheck approach. Individuals positive for CR-AD-specific C-ETACs can be prioritized for further clinical procedures while C-ETAC negative individuals can be considered for alternate diagnoses. The Trucheck approach can eliminate the need for (and risks associated with) invasive colon biopsies in a significant proportion of suspected cases and is especially useful where

scholarly journals Development and Clinical Validation of a Droplet Digital PCR Method for Detection of Acinetobacter baumannii and Klebsiella pneumonia in Patients with Suspected Bloodstream Infections

2021 ◽  
Author(s):  
Yang Zheng ◽  
Jun Jin ◽  
Ziqiang Shao ◽  
Jingquan Liu ◽  
Run Zhang ◽  
...  
Keyword(s):  
Blood Culture ◽  
Acinetobacter Baumannii ◽  
Limit Of Detection ◽  
Early Stage ◽  
Bloodstream Infections ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Klebsiella Pneumonia ◽  
Clinical Validation ◽  
Blood Samples

The relatively long turnaround time and low sensitivity of traditional blood culture may delay the effective antibiotic therapy in patients with bloodstream infection (BSI). To reduce the morbidity and mortality of BSI, a rapid and sensitive pathogen detection method is urgently required. Acinetobacter baumannii and Klebsiella pneumonia are two major microorganisms responsible for BSI. Here we reported a novel droplet digital PCR (ddPCR) method that can detect A. baumannii and K. pneumonia in whole blood samples within 4 h, with a specificity of 100% for each strain and limit of detection at 0.93 copies/microliter for A. baumannii and 0.27 copies/microliter for K. pneumonia. Clinical validation in 170 patients with suspected BSIs showed that, compared with blood culture that reported 4 (2.4%) A. baumannii cases and 7 (4.1%) K. pneumonia cases, ddPCR detected 23 (13.5%) A. baumannii cases, 26 (15.3%) K. pneumonia cases, and 4 (2.4%) dual infection cases, including the 11 positive patients reported by blood culture. In addition, the positive patients reported by ddPCR alone (n = 42) had significantly lower serum concentrations of procalcitonin and lactate, SOFA and APACHE II scores, and 28-day mortality than those reported by both blood culture and ddPCR (n = 11), suggesting that patients with less severe manifestations can potentially benefit from the guidance of ddPCR results. In conclusion, our study suggests that ddPCR represents a sensitive and rapid method to identify causal pathogens in blood samples and to guide the treatment decisions in the early stage of BSI.

scholarly journals Clinical Validation Results of an Innovative Non-Invasive Device for Colorectal Cancer Preventive Screening through Fecal Exhalation Analysis

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1471
Author(s):  
Giulia Zonta ◽  
Cesare Malagù ◽  
Sandro Gherardi ◽  
Alessio Giberti ◽  
Alessandro Pezzoli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Low Cost ◽  
Occult Blood ◽  
Machine Learning Techniques ◽  
Fecal Occult Blood ◽  
Clinical Validation ◽  
Non Invasive ◽  
Fecal Occult ◽  
Incidence And Mortality

Screening is recommended to reduce both incidence and mortality of colorectal cancer. Currently, many countries employ fecal occult blood test (FOBT). In Emilia-Romagna (Italy), since 2005, FOBT immunochemical version (FIT) is performed every two years on people aged between 50 and 69 years. A colonoscopy is then carried out on those who are FIT positive. However, FIT shows approximately 65% false positives (non-tumoral bleedings), leading to many negative colonoscopies. The use of an economic and easy-to-use method to check FOBT-positives will improve screening effectiveness, reducing costs to the national health service. This work illustrates the results of a three-year clinical validation protocol (started in 2016) of a patented device composed of a core of nanostructured gas sensors. This device was designed to identify CRC presence by fecal volatile compounds, with a non-invasive, in vitro and low-cost analysis. Feces are, in fact, affected by tumor-volatile biomarkers, produced by cellular peroxidation and metabolic alterations. The protocol consisted in the analysis of fecal samples of FIT-positive subjects, using colonoscopy as a gold standard. A total of 398 samples were analyzed with machine learning techniques, leading to a sensitivity and specificity of 84.1% and 82.4%, respectively, and a positive predictive value of 72% (25–35% for FIT).

scholarly journals Performance of a MethyLight assay for methylated SFRP2 DNA detection in colorectal cancer tissue and serum

2019 ◽  
Vol 34 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Hui Li ◽  
Zhenzhen Wang ◽  
Guodong Zhao ◽  
Yong Ma ◽  
Ying Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Limit Of Detection ◽  
Methylation Status ◽  
Screening Method ◽  
Cancer Tissue ◽  
Non Invasive ◽  
Cancer Tissues ◽  
Methylight Assay

Background: Colorectal cancer is one of the five most common cancers in China, and its incidence is steadily increasing. An accurate and non-invasive screening method is needed to increase the population uptake of colorectal cancer screening. Secreted frizzled-related protein 2 ( SFRP2) has been found to be hypermethylated in most colorectal cancer patients, and it may fulfill the role of a non-invasive biomarker for colorectal cancer screening. Methods: Methylation status of SFRP2 was examined in 17 cancer tissues and paired adjacent paracancer tissues by a new SFRP2 MethyLight assay, which was also used to test the serum of 62 patients with colorectal cancer and 55 normal individuals. Results: The limit of detection of the SFRP2 MethyLight assay was about 200 pg per reaction. The SFRP2 methylation level was higher in 94.1% colorectal cancer tissues than in paired adjacent paracancer tissues ( P<0.001). The sensitivity and specificity of SFRP2 for detecting colorectal cancer in serum were 69.4% (95% confidence interval (CI) 56.2, 80.1%) and 87.3% (95% CI 74.9, 94.3%), respectively. Conclusion: SFRP2 methylation in serum has the potential to be a non-invasive biomarker for colorectal cancer screening.

scholarly journals Detection of VAR2CSA-Captured Colorectal Cancer Cells from Blood Samples by Real-Time Reverse Transcription PCR

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5881
Author(s):  
Sara R. Bang-Christensen ◽  
Viatcheslav Katerov ◽  
Amalie M. Jørgensen ◽  
Tobias Gustavsson ◽  
Swati Choudhary ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
White Blood Cells ◽  
Amplification Efficiency ◽  
Cell Detection ◽  
Invasive Approach ◽  
Blood Samples ◽  
Highly Sensitive

Analysis of circulating tumor cells (CTCs) from blood samples provides a non-invasive approach for early cancer detection. However, the rarity of CTCs makes it challenging to establish assays with the required sensitivity and specificity. We combine a highly sensitive CTC capture assay exploiting the cancer cell binding recombinant malaria VAR2CSA protein (rVAR2) with the detection of colon-related mRNA transcripts (USH1C and CKMT1A). Cancer cell transcripts are detected by RT-qPCR using proprietary Target Enrichment Long-probe Quantitative Amplified Signal (TELQAS) technology. We validate each step of the workflow using colorectal cancer (CRC) cell lines spiked into blood and compare this with antibody-based cell detection. USH1C and CKMT1A are expressed in healthy colon tissue and CRC cell lines, while only low-level expression can be detected in healthy white blood cells (WBCs). The qPCR reaction shows a near-perfect amplification efficiency for all primer targets with minimal interference of WBC cDNA. Spike-in of 10 cancer cells in 3 mL blood can be detected and statistically separated from control blood using the RT-qPCR assay after rVAR2 capture (p < 0.01 for both primer targets, Mann-Whitney test). Our results provide a validated workflow for highly sensitive detection of magnetically enriched cancer cells.

scholarly journals Quantitative Fluorescence Determination of Long-Fragment DNA in Stool as a Marker for the Early Detection of Colorectal Cancer

2009 ◽  
Vol 31 (1) ◽  
pp. 11-17
Author(s):  
Daniele Calistri ◽  
Claudia Rengucci ◽  
Chiara Molinari ◽  
Enrico Ricci ◽  
Elena Cavargini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pilot Study ◽  
Large Scale ◽  
Dna Analysis ◽  
Invasive Approach ◽  
Dna Test ◽  
Standard Curve ◽  
Non Invasive ◽  
Diagnostic Potential ◽  
Screening Population

Background: A variety of molecular markers have been evaluated for the development of a non-invasive approach to the diagnosis of colorectal cancer. We aimed to validate the diagnostic accuracy, using the same threshold as in the previous pilot study, of fluorescent long DNA test as a relatively simple and inexpensive tool for colorectal cancer detection.Methods: A case-control study was conducted on 100 healthy subjects and 100 patients at first diagnosis of colorectal cancer. Human long-fragment DNA in stool was quantified by fluorescence primers and a standard curve and expressed in DNA nanograms.Results: We validated the 25-ng value, which emerged as the most accurate cut-off in the pilot study, obtaining 79% (95% CI, 71–87%) sensitivity and 89% (95% CI, 83–95%) specificity. Specificity was very high for all cut-off values (15–40 ng) analyzed, ranging from 78 to 96%. Sensitivity was only slightly lower, reaching 84% at the lowest cut-off and maintaining a good level at the higher values. Diagnostic potential was independent of gender, age and tumor site.Conclusion: Fecal DNA analysis is a non-invasive and fairly simple test showing high diagnostic potential. These characteristics, together with the small amount of stool required, make it potentially suitable to be used alongside or as an alternative to current non-invasive screening approaches. Our next step will be to validate these results in a large-scale cohort study of a screening population, which is needed prior to implementation into clinical practice.

Investigations of a novel diagnostic technology for colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 564-564
Author(s):  
Hongmei Tao ◽  
Xuedong Du ◽  
Shijin Ding ◽  
Xing Tang ◽  
Da Lou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sensitivity And Specificity ◽  
Large Population ◽  
Diagnostic Methods ◽  
Control Group ◽  
P Value ◽  
Blood Samples ◽  
Non Invasive ◽  
Cancer Group ◽  
Diagnostic Technology

564 Background: Currently endoscopy examination takes an important role in the diagnosis of colorectal cancer, and there are no other clinically viable non-invasive diagnostic methods. In this investigation, a newly developed, novel IVD cancer diagnostic technology named Cancer Differentiation Analysis (CDA) Technology was investigated for colorectal cancer diagnosis. CDA is a new technology using multi-level and multi-parameter information which measures information relating to both protein fragments and cellular signals in blood samples in one single test. Methods: Peripheral blood was drawn in EDTA tubes for CDA tests. Intravenous blood samples from individuals with colorectal cancer (n = 193), as well as control samples (n = 705) were collected. Cancer group has been clinically diagnosed, and individuals in control group have been confirmed by physical examinations free of cancer. All blood samples were tested using a CDA device, and collected data were analyzed in the SPSS Packages. Results: Data analysis (using T test) showed a significant statistical difference with P value < 0.05 between colorectal cancer group and control group. Details of CDA test results were given in Table 1. Based on initial data, the area under curve (AUC), sensitivity and specificity of CDA technology for colorectal cancer were determined to be 0.861, 76.7% and 76.7% (cut-off value was set at a level at which sensitivity and specificity are comparable), respectively. Conclusions: CDA technology is able to statistically distinguish control group from colorectal cancer group with reasonably high sensitivity and specificity (both above 75%). As a non-invasive and potentially cost effective method capable of large population screening, CDA technology could be a very promising approach for the screening and diagnosis of colorectal cancer. [Table: see text]

scholarly journals BIOM-35. MULTI ANALYTE ASSAY FOR NON-INVASIVE DIAGNOSIS OF BRAIN TUMORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii9-ii9
Author(s):  
Dadasaheb Akolkar ◽  
Darshana Patil ◽  
Pooja Fulmali ◽  
Sneha Puranik ◽  
Sachin Apurwa ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Brain Biopsy ◽  
High Sensitivity ◽  
Tissue Samples ◽  
Invasive Approach ◽  
Non Invasive ◽  
Droplet Pcr ◽  
Asymptomatic Individuals ◽  
Diagnostic Work ◽  
Work Up

Abstract The diagnosis of Central Nervous System (CNS) malignancies such as Gliomas in individuals presenting with Intracranial Space Occupying Lesions (ICSOL) is based on histopathological examination (HPE) of tumor tissue obtained by an invasive brain biopsy. However, brain biopsies are resource intensive and are associated with procedural risks such as haemorrhage, morbidity and mortality. The present study evaluated a non-invasive approach for diagnosis of CNS-M in symptomatic individuals based on evaluation of circulating tumor analytes in peripheral blood. The non-invasive multi-platform approach for diagnosis of CNS-M included Immunocytochemistry (ICC) profiling and Fluorescence in situ Hybridization (FISH) of Circulating Tumor Cells (CTCs) and Digital Droplet PCR (ddPCR) of cell-free tumor DNA (ctDNA) and exosomal mRNA. Performance characteristics of each platform were evaluated using blood and tissue samples from 445 individuals including 227 known cases of CNS-M, 47 known cases of benign CNS conditions (CNS-B), 141 known cases of other cancers with brain metastases (OTH-M) and 30 asymptomatic individuals (ASYM). In a set of 37 samples from individuals with radiological ICSOL, suspected of malignancy (CNS-S) complete diagnostic work-up was performed with ICC, FISH and ddPCR. Glial CTCs were detected in 88.8% of 227 CNS-M and undetectable in 89.4% of 47 CNS-B or 100% of 141 OTH-M, indicating high sensitivity and specificity, respectively. The multi-analyte approach discerned CNS-M from CNS-B as well as OTH-M with 91.7% accuracy and accurately inferred lineage in 84.6% of cases. This non-invasive multi-analyte approach can diagnose CNS-M with an accuracy not inferior to standard HPE, can substitute invasive biopsies in most cases and is particularly helpful in cases where a biopsy is not viable.

Opportunistic Colorectal Cancer Screening using Colonoscopy. Comparative Results between two Historical Cohorts in Bucharest, Romania

2015 ◽  
Vol 24 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Elena Mirela Ionescu ◽  
Tudor Nicolaie ◽  
Serban Ion Gologan ◽  
Ana Mocanu ◽  
Cristina Ditescu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Screening Program ◽  
Advanced Adenoma ◽  
Detection Rates ◽  
Incidence And Mortality ◽  
Organized Screening Program ◽  
History Of ◽  
Comparative Results ◽  
Asymptomatic Individuals ◽  
Second Period

Background & Aims: Even though Romania has one of the highest incidence and mortality in colorectal cancer (CRC) in Europe, there is currently no organized screening program. We aimed to assess the results of our opportunistic CRC screening using colonoscopy.Methods: A single center retrospective study to include all opportunistic screening colonoscopies performed in two 18 month periods (2007-2008 and 2012-2013) was designed. All asymptomatic individuals without a personal or family history of adenoma or CRC and with complete colonoscopy performed in these two time periods were included.Results: We included 1,807 individuals, 882 in the first period, 925 in the second period. There were 389 individuals aged below 50, 1,351 between 50 and 75 and 67 older than 75 years. There were 956 women (52.9%), with a mean age of 58.5 (median 59, range 23-97). The detection rates were 12.6% for adenomas (6.1% for advanced adenoma) and 3.4% for adenocarcinoma. Adenoma incidence (4.9% in subjects under 50, 14.7% in those aged 50 to 75, and 16.4% in those older than 75, p<0.0001) and size (6.3mm in subjects younger than 50, 9.2mm in those 50 to 75 and 10.8mm in those older than 75, p=0.015) significantly increased with age. Adenoma incidence increased in the second period (14.8% vs. 10.3%, p=0.005), while adenoma size decreased in the second period (8.4mm vs. 10mm, p=0.006). There were no procedure related complications.Conclusions: The neoplasia detection rate was 16% (12.6% adenoma, 3.4% adenocarcinoma). Adenoma incidence and size increased with age in both cohorts. In the second screening period significantly more and smaller adenomas were detected.

Fecal microRNAs as non-invasive biomarkers for the detection of colorectal cancer: a systematic review

2019 ◽  
Vol 31 (1) ◽  
Author(s):  
Antonio Francavilla ◽  
Sonia Tarallo ◽  
Barbara Pardini ◽  
Alessio Naccarati
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Non Invasive
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