| BackgroundColorectal cancer(CRC)is one of the most common cancers in the world which was third highest on incidence and second highest on mortality.Advanced adenoma is admittedly premalignant lesions of CRC.Early detection and removal of early CRC and advanced adenoma can decrease the mortality and morbidity of CRC.Fecal immunochemical test(FIT)as a non-invasive and economical method has become the first-line method in CRC screening.The limit of quantitation(LoQ)of conventional quantitative FIT is 50 ng/mL.This LoQ makes it difficult to detect advanced adenoma and CRC with micro-hemorrhages.As a result,the sensitivity of conventional quantitative FIT for CRC is excellent,but for advanced adenoma is ordinary.Many studies have showed that threshold decreasing from 100 to 50 ng/mL can increase the detection for CRC.Therefore,with the cut-off values further decrease to 10 ng/mL,the detection rate for CRC and advanced adenoma could be much more increased.To improve the sensitivity for fecal hemoglobin,increase the detection rate for CRC and advanced adenoma,and reduced the morbidity of CRC,we developed hypersensitivity quantitative FIT(hs-qFIT)through medico engineering cooperation.Compared with the conventional quantitative FIT,the LoQ for hs-qFIT is 10 ng/mL.This LoQ makes it more sensitive and stabilized for detecting hemoglobin.Through detecting more tiny amounts of fecal hemoglobin,hs-qFIT could reduce the missed diagnosis of colonic lesions,and have higher application value in the diagnosis of CRC and advanced adenoma.In this study,we determine the performance characteristics to verified the accuracy and stability of hs-qFIT in low fecal hemoglobin concentration(≥10 ng/mL).What’s more,we assess the application value of hs-qFIT for the first time through the diagnostic efficiency and optimal number of sample in the diagnosis of CRC and advanced adenoma.Part 1 Performance characteristics and evaluation of hs-qFITObjective:We aimed to verify the performance characteristics and application ability of hs-qFIT.Methods:Assess the performance characteristics of hs-qFIT system through the precision,linearity range,carry-over,sensitivity analysis,limit of blank(LoB),limit of detection(LoD),LoQ,hook effect,stability of detection reagents and stability of fecal samples.Results:For hs-qFIT below 10 ng/Ml,the coefficient of variation(CV)of intra-assay precision and inter-day precisions were<10%.The linearity range was 10～280 ng/mL.The carry-over rate was 0.0000068%.The variation of absorbency for sensitivity analysis is in 0.0125～0.0115 mABS.The LoB,LoD,and LoQ were 4.28,4.77 and 10.0 ng/mL.The antigen excess for hook effect appeared in about 663 ng/mL.The CVs of detection reagents were<10%in at least 34 days.For the stability of fecal samples,the CV of repeated detection in one day were 0.45%～2.73%;the CV of repeated detection in 2～8℃ for 7,14 and 21 days were 1,38%～8.24%,1.44%～7.05%and 1.53%～10.39%,and the CV of repeated detection in 25～30℃for 7,14 and 21 days were 0.70%～9.13%,2.90%～29.54%and 3.60%～37.54%.Conclusions:1 The measure range of hs-qFIT was 10～280 ng/mL,and the hs-qFIT could quantitatively measure fecal hemoglobin whose concentration was more than 10 ng/mL without the influence of hook effect and the contamination from high-concentration sample.2 Fecal sample collected by the sample tube could be stored at 2～8℃ for at least 14 days and at 25～30℃ for at least for 7 days.Part 2 Diagnostic efficiency of hs-qFIT for advanced adenoma and colorectal cancer Objective:We aimed to evaluate the diagnostic efficiency of the lower threshold of hs-qFIT for CRC and advanced adenoma.Methods:Consecutive patients scheduled to undergo colonoscopies in Qilu Hospital of Shandong University were prospectively included in this study from July 2020 to December 2020.Patients included in this study were 50～75 years old.All patients were requested to submit fecal samples before colonoscopy within a week.Colonoscopy was the "gold standard".The diagnostic efficiency of hs-qFIT for CRC and advanced adenoma were assessed.Results:Total of 811 patients was involved in this study included 20(2.47%)of CRC,and 47(5.80%)of advanced adenoma.When the cut-offs decreased from 100 to 10 ng/mL,the sensitivities of advanced adenoma increased from 19.1%to 66.0%,and the specificities decreased from 95.0%to 85.1%;the sensitivities for CRC increased from 90.0%to 100.0%,and the specificities decreased from 96.3%to 84.2%.The area under the curve of hs-qFIT for advanced adenoma and CRC were 0.846 and 0.981,and the optimal threshold for advanced adenoma and CRC was 10 and 29 ng/mL.Conclusions:1 The threshold reducing from 50 ng/mL to 10 ng/mL could improve the detection of advanced adenoma and CRC.2 The cut-off at 10 ng/mL had the best diagnostic efficiency for advanced adenoma,which could significantly increase the sensitivity for advanced adenoma.3 Since easier to hemorrhage for CRC than advanced adenoma,the best diagnostic efficiency for CRC was at about 30 ng/mL.Part 3 One-day method and two-day method for hs-qFIT in the diagnosis of colorectal cancer and advanced adenomaObjective:Aim to investigate the optimal number of fecal samples for colorectal cancer and advanced adenoma screening at a lower threshold.Methods:From July 2020 to March 2021,consecutive patients aged 50～75 years who were scheduled to undergo colonoscopies in Qilu Hospital of Shandong University were prospectively included in this study.All patients collected two fecal samples before colonoscopy.The results of the first fecal sample and the higher value of the two samples were regarded as the result of one-day method and two-day method,respectively.The diagnosis efficiencies of the two methods for CRC and advanced adenoma were compared.Results:Total 913 patients including 25(2.7%)of CRC and 56(6.1%)of advanced adenomas were included in this study.At the threshold of 10 ng/mL,the sensitivity of one-day and two-day method for CRC were 84.0%and 100.0%(P=0.134),and the specificity were 90.1%and 83.9%(P<0.001),respectively.The sensitivity of one-day and two-day method for advanced adenoma were 33.9%and 66.1%(P<0.001),and the specificity were 89.5%and 84.7%(P<0.001),respectively.The area under the curve of one-day and two-day method for CRC were 0.949 and 0.983,P=0.041,for advanced adenoma were 0.780 and 0.833,P=0.032,respectively.Conclusions:1 Compared with one-day method,the positive rate of two-day method was increased,which could increase the diagnostic efficiency for CRC and advanced adenoma.2 At the threshold of 10 ng/mL,two-day method could not increase the detection rate significantly,and one-day method was optimal for the diagnosis of CRC;the two-day method could increase the detection rate significantly,which optimal for the diagnosis of advanced adenoma. |
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