Double sampling of a faecal immunochemical test is not superior to single sampling for detection of colorectal neoplasia: a colonoscopy controlled prospective cohort study

<p>Abstract</p> <p>Background</p> <p>A single sampled faecal immunochemical test (FIT) has moderate sensitivity for colorectal cancer and advanced adenomas. Repeated FIT sampling could improve test sensitivity. The aim of the present study is to determine whether any of three different strategies of double FIT sampling has a better combination of sensitivity and specificity than single FIT sampling.</p> <p>Methods</p> <p>Test performance of single FIT sampling in subjects scheduled for colonoscopy was compared to double FIT sampling intra-individually. Test positivity of double FIT sampling was evaluated in three different ways: 1) "one of two FITs+" when at least one out of two measurements exceeded the cut-off value, 2) "two of two FITs+" when both measurements exceeded the cut-off value, 3) "mean of two FITs+" when the geometric mean of two FITs exceeded the cut-off value. Receiver operator curves were calculated and sensitivity of single and the three strategies of double FIT sampling were compared at a fixed level of specificity.</p> <p>Results</p> <p>In 124 of 1096 subjects, screen relevant neoplasia (SRN) were found (i.e. early stage CRC or advanced adenomas). At any cut-off, "two of two FITs+" resulted in the lowest and "one of two FITs+" in the highest sensitivity for SRN (range 35-44% and 42%-54% respectively). ROC's of double FIT sampling were similar to single FIT sampling. At specificities of 85/90/95%, sensitivity of any double FIT sampling strategy did not differ significantly from single FIT (p-values 0.07-1).</p> <p>Conclusion</p> <p>At any cut off, "one of two FITs+" is the most sensitive double FIT sampling strategy. However, at a given specificity level, sensitivity of any double FIT sampling strategy for SRN is comparable to single FIT sampling at a different cut-off value. None of the double FIT strategies has a superior combination of sensitivity and specificity over single FIT.</p

Fecal volatile organic compounds for early detection of colorectal cancer: where are we now?

Introduction: The fecal volatolome, which is composed of fecal volatile organic compounds (VOCs), seems to hold potential as non-invasive biomarker for the detection of colorectal cancer (CRC) and its precursor lesions advanced adenomas (AA). The potential of the fecal volatolome has been subject of various studies using either chemical analytical or pattern-recognition techniques. The available literature on the potential of the fecal volatolome as CRC and AA biomarker was reviewed. Methods: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, Google Scholar and ResearchGate using the following keywords: Colorectal Cancer, Advanced Adenoma, Volatile Organic Compound, Metabolome, Gas Chromatrography–Mass Spectrometry, Selected-Ion Flow-Tube Mass Spectrometry, eNose, and Fecal Biomarkers. Results: Eighty-eight titles or abstracts were identified from the search, of which 11 papers describing the potential of the fecal volatolome for CRC detection were selected. In these studies, different techniques were used for the headspace analyses of fecal VOCs, limiting the possibility to compare outcomes. Increased levels of amino acids and short chain fatty acids, and decreased levels of bile acids and polyol alcohols in the gas phase of feces were observed repeatedly. All selected papers reported high diagnostic value for the detection of both CRC and AA based on fecal VOCs. Conclusion: Based on the included studies, fecal VOC analyses seem promising for future screening of CRC and AA, with potentially improved test performances allowing for earlier detection of AA and CRC and consequently earlier initiation of treatment, possibly reducing morbidity and mortality rates next to lower rates of (unnecessary) colonoscopies

The scent of colorectal cancer: detection by volatile organic compound analysis

The overall metabolic state of an individual is reflected by emitted volatile organic compounds (VOCs), which are gaseous carbon-based chemicals. In this review, we will describe the potential of VOCs as fully noninvasive markers for the detection of neoplastic lesions of the colon. VOCs are detected by our sensory olfactory nerves and form the molecular basis for our sense of smell. As such, we emit our own individual odor fingerprint or so-called smellprint. This may change over time in response to any alteration in metabolism such as modifications caused by gastrointestinal infection, inflammation, external factors such as medication and diet, or development of neoplastic disease such as colorectal cancer. This means that analysis of VOCs can provide a fully noninvasive metabolomics biomarker profile that could be used as a diagnostic tool. Thus far, canine scent detection, gas chromatography-mass spectrometry, and electronic nose technologies allow for discrimination between patients with and without colorectal cancer and also its precursor (advanced adenoma) with promising accuracy. The challenge for future research is to identify specific biomarkers driving these signals. This enables the development of primed sensors tailored toward accurate identification of volatiles specific to colorectal cancer and adenomas. Such a technique may allow noninvasive monitoring of response to therapy and could revolutionize screening practices for colorectal cancer and potentially many other gastrointestinal disease