Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC-MS) for identification and quantification of volatile organic compounds (VOCs). The T-test was used to identify significant VOCs (p values < 0.017). The second technique relied on sensor analysis with a pattern recognition method for building a breath pattern to identify different groups. Blind analysis or leave-one-out cross validation was conducted for validation. The GC-MS analysis revealed four significant VOCs that identified the tested groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4-methyl octane (lower in CRC). The sensor-analysis distinguished CRC from the control group with 85% sensitivity, 94% specificity and 91% accuracy. The performance of the sensors in identifying the advanced adenoma group from the non-advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The performance of the sensors in identifying the advanced adenoma group was distinguished from the control group was 100% sensitivity, 88% specificity, and 94% accuracy. For summary, volatile marker testing by using sensor analysis is a promising noninvasive approach for CRC screening.Globally colorectal cancer (CRC) is the third most prevalent cancer and the fourth leading cause of death from malignant diseases. 1 The 5-year survival rate for colorectal cancer when diagnosed at an early stage before it has spread is about 90%. But only about four out of 10 colorectal cancers are found at that early stage. In advanced stages, the survival rates are substantially lower. Therefore, regular CRC screening or testing are considered as some of the most powerful tools for preventing colorectal cancer caused mortality. 2 Not only does CRC screening save lives, but it also is cost effective. Studies have shown that the cost-effectiveness of CRC screening is consistent with many other kinds of preventive services and is lower than some common interventions. 3 The laboratory-based faecal immunochemical test (FIT) is the test-of-choice currently in the EU. 4 Alternatively, several recent studies have demonstrated the ability of flexiblesigmoidoscopy to decrease the disease-specific mortality when used as a screening tool. 5-7 However, colonoscopy is considered better than sigmoidoscopy in preventing mortality. 8 Poland, Germany and Czech Republic are using colonoscopy as their primary screening tool. Nevertheless, the major problem with endoscopic methods for CRC screening is low compliance. 9 A systemic review of participation in CRC screening within trial settings after the first-time invitation has reported only...
IntroductionPopulation-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40–64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome.Methods and analysisIndividuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase.Ethics and disseminationThe study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberNCT02047994
Background Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy. Methods We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex-agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs. histological diagnosis were calculated using both the manufacturers’ and optimized cutoffs. Results Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all p-values<0.01). Based on manufacturers’ cutoffs, sensitivities, specificities and areas under the ROC curve for detecting moderate to severe histological corpus atrophy by PgI/PgII were 44%/91%/0.70, 56%/84%/0.76, and 52%/90%/0.77 for Biohit, Vector Best and Eiken, respectively. Cutoffs optimized by ROC or data mining analyses did not substantially improve test-performance. Conclusions Commercial assays for pepsinogen have good relative agreement but are imperfect tests for clinical diagnosis of gastric atrophy. Impact Pepsinogen testing alone does not provide sufficient information for gastric cancer risk stratification. Future investigations should focus on other potential markers, in combination with pepsinogens.
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