BACKGROUND Certain subgroups are at an increased risk of false fecal immunochemical test(FIT)results;however,related studies are limited,and the available evidence is conflicting.AIM To evaluate factors associated wit...BACKGROUND Certain subgroups are at an increased risk of false fecal immunochemical test(FIT)results;however,related studies are limited,and the available evidence is conflicting.AIM To evaluate factors associated with false-positive and false-negative FIT results.METHODS This retrospective study was based on the database of the Tianjin Colorectal Cancer Screening Program from 2012 to 2020.A total of 4129947 residents aged 40-74 years completed at least one FIT.Of these,24890 asymptomatic participants who underwent colonoscopy examinations and completed lifestyle questionnaires were included in the analysis.Multivariable logistic regression was performed to identify the factors associated with false FIT results.RESULTS Among the overall screening population,88687(2.15%)participants tested positive for FIT.The sensitivity,specificity,positive predictive value,and negative predictive value of FIT for advanced neoplasms were 58.2%,44.8%,9.7%,and 91.3%,respectively.Older age,female sex,smoking,alcohol consumption,higher body mass index,and hemorrhoids were significantly associated with increased odds of false-positive and lower odds of falsenegative FIT results.Moreover,features of high-grade dysplasia or villous for advanced adenoma and the presence of cancer were also associated with lower odds of false-negative results,while irregular exercise and diverticulum were associated with higher odds of false-positive results.CONCLUSION FIT results may be inaccurate in certain subgroups.Our results provide important evidence for further individualization of screening strategies.展开更多
BACKGROUND The quantitative faecal immunochemical test for haemoglobin(FIT) has been revealed to be highly accurate for colorectal cancer(CRC) detection not only in a screening setting, but also in the assessment of p...BACKGROUND The quantitative faecal immunochemical test for haemoglobin(FIT) has been revealed to be highly accurate for colorectal cancer(CRC) detection not only in a screening setting, but also in the assessment of patients presenting lower bowel symptoms. Therefore, the National Institute for Health and Care Excellence has recommended the adoption of FIT in primary care to guide referral for suspected CRC in low-risk symptomatic patients using a 10 μg Hb/g faeces threshold.Nevertheless, it is unknown whether FIT′s accuracy remains stable throughout the broad spectrum of possible symptoms.AIM To perform a systematic review and meta-analysis to assess FIT accuracy for CRC detection in different clinical settings.METHODS A systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2018 to conduct a meta-analysis of prospective studies including symptomatic patients that evaluated the diagnostic accuracy of quantitative FIT for CRC detection. Studies were classified on the basis of brand,threshold of faecal haemoglobin concentration for a positive test result,percentage of reported symptoms(solely symptomatic, mixed cohorts) and CRC prevalence(< 2.5%, ≥ 2.5%) to limit heterogeneity and perform subgroup analysis to assess the influence of clinical spectrum on FIT′s accuracy to detect CRC.RESULTS Fifteen cohorts including 13073 patients(CRC prevalence 0.4% to 16.8%) were identified. Pooled estimates of sensitivity for studies using OC-Sensor at 10 μg Hb/g faeces threshold(n = 10400) was 89.6% [95% confidence interval(CI): 82.7%to 94.0%). However, pooled estimates of sensitivity for studies formed solely by symptomatic patients(n = 4035) and mixed cohorts(n = 6365) were 94.1%(95%CI: 90.0% to 96.6%) and 85.5%(95%CI: 76.5% to 91.4%) respectively(P <0.01), while there were no statistically significant differences between pooled sensitivity of studies with CRC prevalence < 2.5%(84.9%, 95%CI: 73.4% to 92.0%)and ≥ 2.5%(91.7%, 95%CI: 83.3% to 96.1%)(P = 0.25). At the same threshold, OCSensor? sensitivity to rule out any significant colonic lesion was 78.6%(95%CI:75.6% to 81.4%). We found substantial heterogeneity especially when assessing specificity.CONCLUSION The results of this meta-analysis confirm that, regardless of CRC prevalence,quantitative FIT is highly sensitive for CRC detection. However, FIT ability to rule out CRC is higher in studies solely including symptomatic patients.展开更多
AIM To evaluate the efficacy of quantitative fecal immunochemical test(FIT) as biomarker of disease activity in ulcerative colitis(UC).METHODS Between February 2013 and November 2014, a total of 82 FIT results, obtain...AIM To evaluate the efficacy of quantitative fecal immunochemical test(FIT) as biomarker of disease activity in ulcerative colitis(UC).METHODS Between February 2013 and November 2014, a total of 82 FIT results, obtained in conjunction with colonoscopies, were retrospectivelyevaluated for 63 patients with UC. The efficacy of FIT for evaluation of disease activity was compared to colonoscopic findings. Quantitative fecal blood with automated equipment examined from collected feces. Endoscopic disease severity were assessed using the Mayo endoscopic subscore(MES) classification. The extent of disease were classified by proctitis(E1), left sided colitis(E2), and extensive colitis(E3). Clinical activity were subgrouped by remission or active.RESULTS All of 21 patients with MES 0 had negative FIT(< 7 ng/mL), but 22 patients with MES 2 or 3 had a mean FIT of > 134.89 ng/m L. The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) and accuracy of negative FIT about mucosal healing were 73.33%, 81.82%, 91.49%, 51.43% and 73.17%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of predictive value of positive FIT(cutoff value > 100 ng/mL) about active disease status were 45.45%, 93.33%, 71.43%, 82.35%and 26.83%, respectively. Among patients with clinical remission, FIT was negative in 31(81.6%) of 38 cases, with a mean fecal hemoglobin concentration of 6.12 ng/mL(range, negative to 80.9 ng/mL) for this group of patients. Among patients with clinical active disease, FIT was negative in 16(36.4%) out of 44 cases, with a mean fecal hemoglobin concentration > 167.4 ng/mL for this group of patients. FIT was positively correlated with endoscopic activity(r = 0.626, P < 0.01) and clinical activity(r = 0.496, P < 0.01). But, FIT did not correlate with the extent of disease(r =-0.047, P = 0.676)CONCLUSION Quantitative FIT can be a non-invasive and effective biomarker for evaluation of clinical and endoscopic activity in UC, but not predict the extent of disease.展开更多
Objective:Integration of risk stratification into fecal immunochemical test(FIT)might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer(CRC)screening.A comparative study was conducted t...Objective:Integration of risk stratification into fecal immunochemical test(FIT)might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer(CRC)screening.A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment(QRA)and FIT,FIT-only and QRA-only strategies in a CRC screening program in China.Methods:The study included 29,626 individuals aged 40-74 years and invited to participate in a CRC screening program in China.Participants were first invited to undertake QRA and one-time FIT(OC-sensor).Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy.Participation,detection rate,and resource demand for colonoscopy were calculated and compared.Results:Of the 29,626 invitees,20,203 completed the parallel combination,8,592 completed the QRA-only,and11 completed the FIT-only strategy.For the parallel combination,FIT-only,and QRA-only strategies,the overall positivity rates were 10.2%(2,928/28,806),5.4%(1,096/20,214),and 6.8%(1,944/28,795),respectively;the yield of advanced neoplasm per 10,000 invitees were 46.9[95%confidence interval(95%CI):39.8-55.4],36.8(95%CI:30.5-44.4),and 12.2(95%CI:8.8-16.8),respectively;the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7%(95%CI:4.0%-5.6%),9.9%(95%CI:8.3%-11.9%),and 1.9%(95%CI:1.3%-2.6%),respectively;the number of colonoscopies required to detect one advanced neoplasm was 11.4(95%CI:9.8-13.4),5.7(95%CI:4.8-6.7),and 28.4(95%CI:20.7-39.2),respectively.Conclusions:The parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.展开更多
Faecal immunochemical tests(FITs)are the most widely colorectal cancer(CRC)diagnostic biomarker available.Many population screening programmes are based on this biomarker,with the goal of reducing CRC mortality.Moreov...Faecal immunochemical tests(FITs)are the most widely colorectal cancer(CRC)diagnostic biomarker available.Many population screening programmes are based on this biomarker,with the goal of reducing CRC mortality.Moreover,in recent years,a large amount of evidence has been produced on the use of FIT to detect CRC in patients with abdominal symptoms in primary healthcare as well as in surveillance after adenoma resection.The aim of this review is to highlight the available evidence on these two topics.We will summarize the evidence on diagnostic yield in symptomatic patients with CRC and significant colonic lesion and the different options to use this(thresholds,brands,number of determinations,prediction models and combinations).We will include recommendations on FIT strategies in primary healthcare proposed by regulatory bodies and scientific societies and their potential effects on healthcare resources and CRC prognosis.Finally,we will show information regarding FIT-based surveillance as an alternative to endoscopic surveillance after high-risk polyp resection.To conclude,due to the coronavirus disease 2019 pandemic,FIT-based strategies have become extremely relevant since they enable a reduction of colonoscopy demand and access to the healthcare system by selecting individuals with the highest risk of CRC.展开更多
AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.METHODS: The clinical outcomes of 194 UC patients in clinic...AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results.RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.展开更多
AIM:To examine the feasibility of predicting the flareup of ulcerative colitis (UC) before symptoms emerge using the immunochemical fecal occult blood test (IFOBT).METHODS:We prospectively measured fecal hemoglobin co...AIM:To examine the feasibility of predicting the flareup of ulcerative colitis (UC) before symptoms emerge using the immunochemical fecal occult blood test (IFOBT).METHODS:We prospectively measured fecal hemoglobin concentrations in 78 UC patients using the I-FOBT every 1 or 2 mo.RESULTS:During a 20 mo-period,823 fecal samples from 78 patients were submitted.The median concentration of fecal hemoglobin was 41 ng/mL (range:0-392 500 ng/mL).There were three types of patients with regard to the correlation between I-FOBT and patient symptoms;the synchronous transition type with symptoms (44 patients),the unrelated type withsymptoms (19 patients),and the flare-up predictive type (15 patients).In patients with the flare-up predictive type,the values of I-FOBT were generally low during the study period with stable symptoms.Two to four weeks before the flare-up of symptoms,the I-FOBT values were high.Thus,in these patients,I-FOBT could predict the flare-up before symptoms emerged.CONCLUSION:Flare-up could be predicted by I-FOBT in approximately 20% of UC patients.These results warrant periodical I-FOBT in UC patients.展开更多
BACKGROUND Faecal immunochemical test(FIT)has been recommended to assess symptomatic patients for colorectal cancer(CRC)detection.Nevertheless,some conditions could theoretically favour blood originating in proximal a...BACKGROUND Faecal immunochemical test(FIT)has been recommended to assess symptomatic patients for colorectal cancer(CRC)detection.Nevertheless,some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized.A positive FIT result could be related to other gastrointestinal cancers(GIC).AIM To assess the risk of GIC detection and related death in FIT-positive symptomatic patients(threshold 10μg Hb/g faeces)without CRC.METHODS Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection.Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare,underwent a quantitative FIT before undergoing a complete colonoscopy.Patients without CRC were divided into two groups(positive and negative FIT)using the threshold of 10μg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research.We determined the cumulative risk of GIC,CRC and upper GIC.Hazard rate(HR)was calculated adjusted by age,sex and presence of significant colonic lesion.RESULTS We included 2709 patients without CRC and a complete baseline colonoscopy,730(26.9%)with FIT≥10μgr Hb/gr.During a mean time of 45.5±20.0 mo,a GIC was detected in 57(2.1%)patients:An upper GIC in 35(1.3%)and a CRC in 14(0.5%).Thirty-six patients(1.3%)died due to GIC:22(0.8%)due to an upper GIC and 9(0.3%)due to CRC.FIT-positive subjects showed a higher CRC risk(HR 3.8,95%CI:1.2-11.9)with no differences in GIC(HR 1.5,95%CI:0.8-2.7)or upper GIC risk(HR 1.0,95%CI:0.5-2.2).Patients with a positive FIT had only an increased risk of CRC-related death(HR 10.8,95%CI:2.1-57.1)and GIC-related death(HR 2.2,95%CI:1.1-4.3),with no differences in upper GIC-related death(HR 1.4,95%CI:0.6-3.3).An upper GIC was detected in 22(0.8%)patients during the first year.Two variables were independently associated:anaemia(OR 5.6,95%CI:2.2-13.9)and age≥70 years(OR 2.7,95%CI:1.1-7.0).CONCLUSION Symptomatic patients without CRC have a moderate risk increase in upper GIC,regardless of the FIT result.Patients with a positive FIT have an increased risk of post-colonoscopy CRC.展开更多
AIM: To measure the compliance of an Academic Hospital staff with a colorectal cancer(CRC) screening program using fecal immunochemical test(FIT).METHODS: All employees of 'Attikon' University General Hospital...AIM: To measure the compliance of an Academic Hospital staff with a colorectal cancer(CRC) screening program using fecal immunochemical test(FIT).METHODS: All employees of 'Attikon' University General Hospital aged over 50 years were thoroughly informed by a team of physicians and medical students about the study aims and they were invited to undergo CRC screening using two rounds of FIT(DyoniFOB~ Combo H, DyonMed SA, Athens, Greece). The tests were provided for free and subjects tested positive were subsequently referred for colonoscopy. One year after completing the two rounds, participants were asked to be re-screened by means of the same test.RESULTS: Among our target population consisted of 211 employees, 59(27.9%) consented to participate, but only 41(19.4%) and 24(11.4%) completed the first and the second FIT round, respectively. Female gender was significantly associated with higher initial participation(P = 0.005) and test completion- first and second round-(P = 0.004 and P = 0.05) rates, respectively. Phy sician’s(13.5% vs 70.2%, P < 0.0001) participation and test completion rates(7.5% vs 57.6%, P < 0.0001 for the first and 2.3% vs 34%, P < 0.0001 for the second round) were significantly lower compared to those of the administrative/technical staff. Similarly, nurses participated(25.8% vs 70.2%, P = 0.0002) and completed the first test round(19.3% vs 57.6%, P = 0.004) in a significant lower rate than the administrative/technical staff. One test proved false positive. No participant repeated the test one year later.CONCLUSION: Despite the well-organized, guided and supervised provision of the service, the compliance of the Academic Hospital personnel with a FIT-based CRC screening program was suboptimal, especially among physicians.展开更多
The anti-chlorpyrifos polyclonal antibodies were obtained by using the artificial immuneantigen to immune in New Zealands white rabbits. The enzyme-tagged antibodies wereprepared by coupling horseradish peroxidase (HR...The anti-chlorpyrifos polyclonal antibodies were obtained by using the artificial immuneantigen to immune in New Zealands white rabbits. The enzyme-tagged antibodies wereprepared by coupling horseradish peroxidase (HRP) to the purified antibody with themodified sodium periodate method. The indirect competitive enzyme linked immuno-sorbentassays (ELISA) and the HRP-tagged antibody direct ELISA (E-Ab) were established, respectively.The limit of detection (LOD) for the indirect ELISA and E-Ab were 0.0033 and 0.0042 gmL-1, respectively. The linear detection ranged well from 0.005 to 2.0 g mL-1.展开更多
Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistoc...Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistochemical technique. The trace P-450HSj isozyme (Mr. 51.5 Kd) was found in human gastric mucosa. It was similar to P-450j in molecular weight, catalytic and immunochemical properties. The concentrations of P-450HSj in mucosa of lesser curvature were higher than those in greater curvature. This might be one of the important reasons that lesser curvature is the commonest area for gastric carcinoma. But there was possibly less P-450HSj in gastric mucosa with cancer. Im-munohistochemically, P-450HSj was discovered in the cytoplasm of some glandular epithelial cells, especially in the glands with hyperplastic and intestinal metaplastic changes adjacent to carcinoma. It was also found in some normal glands and in tumor cells of high-differentiated adenocarcinoma, but not in those of low-differentiated ones. Following subjects are discussed: (1) the method of detecting trace P-450HSj, (2) the rule of distribution of P-450HSj, and (3) the relationship between the isozyme and the occurrence of gastric cancer caused by nitrosa-mines.展开更多
BACKGROUND For optimizing fecal immunochemical test(FIT)-based screening programs,reducing the rate of missed colorectal cancers(CRCs)by FIT(FIT-interval CRCs)is an important aspect.Knowledge of the molecular make-up ...BACKGROUND For optimizing fecal immunochemical test(FIT)-based screening programs,reducing the rate of missed colorectal cancers(CRCs)by FIT(FIT-interval CRCs)is an important aspect.Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all(precursor)lesions.AIM To compare the molecular make-up of FIT-interval CRCs to lesions that are detected by FIT[screen-detected CRCs(SD-CRCs)].METHODS FIT-interval CRCs observed in a Dutch pilot-program of FIT-based screening were compared to a control group of SD-CRCs in a 1:2 ratio,resulting in 27 FIT-interval CRC and 54 SD-CRCs.Molecular analyses included microsatellite instability(MSI),CpG island methylator phenotype(CIMP),DNA sequence mutations and copy number alterations(CNAs).RESULTS Although no significant differences were reached,FIT-interval CRCs were more often CIMP positive and MSI positive(33%CIMP in FIT-interval CRCs vs 21%in SD-CRCs(P=0.274);19%MSI in FIT-interval CRCs vs 12%in SD-CRCs(P=0.469)),and showed more often serrated pathway associated features such as BRAF(30%vs 12%,P=0.090)and PTEN(15%vs 2.4%,P=0.063)mutations.APC mutations,a classic feature of the adenoma-carcinoma-sequence,were more abundant in SD-CRCs(68%vs 40%in FIT-interval CRCs P=0.035).Regarding CNAs differences between the two groups;FIT-interval CRCs less often showed gains at the regions 8p11.22-q24.3(P=0.009),and more often gains at 20p13-p12.1(P=0.039).CONCLUSION Serrated pathway associated molecular features seem to be more common in FIT-interval CRCs,while classic adenoma carcinoma pathway associated molecular features seem to be more common in SD-CRCs.This indicates that proximal serrated lesions may be overrepresented among FITinterval CRCs.展开更多
BACKGROUND The incidence of colorectal cancer(CRC)in China is steadily rising,with a high proportion of advanced-stage diagnoses.This highlights the significance of early detection and prevention measures to enhance s...BACKGROUND The incidence of colorectal cancer(CRC)in China is steadily rising,with a high proportion of advanced-stage diagnoses.This highlights the significance of early detection and prevention measures to enhance survival rates.Fecal immunochemical testing(FIT)is a globally recommended CRC screening method;however,limited research has been conducted on its application in Hainan.AIM To assess the efficacy and adherence of FIT screening among average-risk individuals in Hainan,while also examining the risk factors associated with positive FIT results.METHODS This population-based cross-sectional study implemented FIT screening for CRC in 2000 asymptomatic participants aged 40-75 years from five cities and 21 community health centers in Hainan Province.The study was conducted from August 2022 to April 2023,employing a stratified sampling method to select participants.Individuals with positive FIT results subsequently underwent colonoscopy.Positive predictive values for confirmed CRC and advanced adenoma were calculated,and the relationship between relevant variables and positive FIT results was analyzed usingχ2 tests and multivariate logistic regression.RESULTS A total of 1788 participants completed the FIT screening,with a median age of 57 years(interquartile range:40-75).Among them,503(28.1%)were males,and 1285(71.9%)were females,resulting in an 89.4%compliance rate for FIT screening.The overall positivity rate of FIT was 4.4%[79 out of 1788;95%confidence interval(CI):3%-5%].The specific positivity rates for Haikou,Sanya,Orient City,Qionghai City,and Wuzhishan City were 9.6%(45 of 468;95%CI:8%-11%),1.3%(6 of 445;95%CI:0.1%-3.1%),2.7%(8 of 293;95%CI:1.2%-4.3%),3.3%(9 of 276;95%CI:1.0%-6.3%),and 4.2%(11 of 406;95%CI:1.2%-7.3%),respectively.Significant associations were found between age,dietary habits,and positive FIT results.Out of the 79 participants with positive FIT results,55 underwent colonoscopy,demonstrating an 82.2%compliance rate.Among them,10 had a clean gastrointestinal tract,43 had polyps or adenomas,and 2 were confirmed to have CRC,yielding a positive predictive value of 3.6%(95%CI:0.9%-4.2%).Among the 43 participants with polyps or adenomas,8 were diagnosed with advanced adenomas,resulting in an advanced adenoma rate of 14.5%(95%CI:10.1%-17.7%).CONCLUSION In the Hainan region,FIT screening for CRC among asymptomatic individuals at average risk is feasible and wellreceived.展开更多
Metallothioneins in Caenorhahditis elegans (CeMT-Ⅰ and Ⅱ) were punned by the combination of gel filtration ion-exchange chromatography.and high-performance liquid chromatography.Amino acid compositions and amino-ter...Metallothioneins in Caenorhahditis elegans (CeMT-Ⅰ and Ⅱ) were punned by the combination of gel filtration ion-exchange chromatography.and high-performance liquid chromatography.Amino acid compositions and amino-terminal sequences of CeMT-Ⅰ and Ⅱ were slightly different from those of vertebrate MTs previously reported, although cysteine residue contents were relatively high.Enzyme immunoassay using anti-CeMT-Ⅱ antibody showed the difference of antigenicity to rat MT-Ⅰ and Ⅱ and even to CeMT-Ⅰ. Immunohistochemical staining revealed the existence of CeMT-Ⅱ in the intestine and the eggs, suggesting the role of MT in detoxification and homeostasis of heavv metals. 1990 Academic Press.Inc.展开更多
The formation of covalent adducts as a result of the interaction of metabolically activated chemicals with host macromolecules is a common critical event in mutagenic, carcinogenic, and immunologic phenomena. Because ...The formation of covalent adducts as a result of the interaction of metabolically activated chemicals with host macromolecules is a common critical event in mutagenic, carcinogenic, and immunologic phenomena. Because of their antigenicity and their immunogenicity, covalent adducts may be detected using sensitive immunochemical techniques. The immunochemical approaches to biomonitoring and molecular dosimetry of DNA damage are particularly attractive because they allow sensitive quantitation of specific DNA adducts present in small samples and do not rely on the use of radiolabeled adducts. Two examples of biomarker immunoassay development are presented: an avidin/biotin-amplified ELISA for the major DNA adduct of the human bladder carcinogen 4-aminobiphenyl (ABP), and a particle concentration fluorescent immunoassay (PCFIA) for the major protein adduct associated with toxicity by the prototype hepatotoxin acetaminophen. The examples illustrate critical steps in the development of biomarker immunoassays which include selection of the relevant adduct, preparation of an appropriate immunogen, immunization, characterization of antisera, and development of application-specific sample processing techniques for biomarker quantitation. Immunochemical procedures may be combined with other analytical techniques to form hybrid systems which take advantage of both the antigenicity and the physical or chemical properties of a biomarker to achieve greater specificity and/or sensitivity. The future usefulness of these new tools of molecular epidemiology will depend on a compound-by-compound validation of methods and critical evaluation of the biologic importance of the particular antigenic biomarker as an indicator of exposure and as an indicator of risk.展开更多
AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective coh...AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.展开更多
Screening for colorectal cancer(CRC)has the potential to strongly reduce incidence and mortality of this common cancer[1,2].While fecal tests have long been established as non-invasive CRC screening tests,an intensive...Screening for colorectal cancer(CRC)has the potential to strongly reduce incidence and mortality of this common cancer[1,2].While fecal tests have long been established as non-invasive CRC screening tests,an intensive search for blood-based tests,which have been claimed to be easier to integrate into routine medical practice,is underway[3,4].Most recently,clinical validation of a circulating tumor DNA-based blood test for the detection of patterns of CpG(cytosine followed by guanine)dinucleotidemethylation has been reported from the PREEMPT CRC study,a large,United States(US)based screening study including 27,010 participants of screening colonoscopy[4].The study was sponsored by the manufacturer and reported with limited details about the laboratory analyses.With a sensitivity of 79.2%(95%confidence interval[CI],68.4%-86.9%)for CRC detection and a specificity of 91.5%(95%CI,91.2%-91.9%)for advanced colorectal neoplasia,the test met the pre-specified acceptance criteria,but the sensitivity for detecting advanced precancerous lesions(APCL)was low(12.5%).We aimed to compare the reported diagnostic performance of this blood-based test with that of the fecal immunochemical test(FIT),the best established and globally most widely used non-invasive CRC test[5],in a large population of screening colonoscopy participants from Germany.展开更多
Background:Fecal immunochemical tests(FITs)are the most widely used non-invasive tests in colorectal cancer(CRC)screening.However,evidence about the direct comparison of the test performance of the self-administered q...Background:Fecal immunochemical tests(FITs)are the most widely used non-invasive tests in colorectal cancer(CRC)screening.However,evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse.Methods:Based on a CRC screening trial(TARGET-C),we included 3144 pre-colonoscopy fecal samples,including 24 CRCs,230 advanced adenomas,622 non-advanced adenomas,and 2268 participants without significant findings at colonoscopy.Three selfadministered qualitative FITs(Pupu tube)with positivity thresholds of 8.0,14.4,or 20.8 mg hemoglobin(Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT(OC-Sensor)with a positivity threshold of 20 mg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory.The diagnostic performance of the FITs for detecting colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds(for the quantitative FIT).Results:At the thresholds preset by the manufacturers,apart from the qualitative FIT-3,significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1(33.9%[95%CI:28.7–39.4%])and qualitative FIT-2(22.2%[95%CI:17.7–27.2%])compared to the quantitative FIT(11.7%[95%CI:8.4–15.8%]),while at a cost of significantly lower specificities.However,such difference was not observed for detecting CRC.For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly,there were no significant differences in terms of sensitivity,specificity,positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs,which was further evidenced in ROC analysis.Conclusions:Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the positivity thresholds preset by the manufacturer,such heterogeneity could be overcome by adjusting thresholds to yield comparable specificities or positivity rates.Future CRC screening programs should select appropriate types of FITs and define the thresholds based on the targeted specificities and manageable positivity rates.展开更多
Objective:To explore the performance of a protocol combining fecal immunochemical test(FIT)and a high-risk factor questionnaire(HRFQ)for selecting patients requiring colonoscopy as part of a population-based colorecta...Objective:To explore the performance of a protocol combining fecal immunochemical test(FIT)and a high-risk factor questionnaire(HRFQ)for selecting patients requiring colonoscopy as part of a population-based colorectal cancer(CRC)screening program in China.Methods:From 2015 to 2016,we conducted a CRC screening program for all residents aged 45 years or older in Tianhe District,Guangzhou City,China.Participants underwent an FIT and received an HRFQ as part of primary screening.Those with positive FIT and/or HRFQ results were considered to be at high risk and were recommended to undergo colonoscopy.Results:A total of 10074 subjects were recruited and enrolled in the screening program.In the enrolled population,17.5%had positive FIT results and 19.4%had positive HRFQ results.Of those recommended to undergo diagnostic colonoscopy,773 did so.The screening method’s overall positive predictive value(PPV)was 4.9%for non-adenomatous polyps,11.4%for low-risk adenomas(LRAs),15.9%for high-risk adenomas(HRAs)and 1.6%for CRC.The PPVs of positive FIT results for nonadenomatous polyps,LRAs,HRAs and CRC were 5.2%,15.9%,22.5%and 2.5%,respectively.The PPVs of positive HRFQ results for non-adenomatous polyps,LRA,HRA and CRC were 4.1%,10.2%,14.3%and 1.4%,respectively.The PPVs associated with combined positive FIT and HRFQ results for non-adenomatous polyps,LRAs,HRAs and CRC were 4.5%,16.4%,23.7%and 2.8%,respectively.Conclusion:Our results suggest that this two-step CRC screening strategy,involving a combination of FIT and HRFQ followed by colonoscopy,is useful to identify early-stage CRC.The high detection rates and PPVs for CRC and adenomas encourage this strategy’s use in ongoing screening programs.展开更多
Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco ...Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco smoking,alco-hol consumption,and unhealthy diet.CRC screening methods vary considerably between countries and depend on incidence,economic resources and healthcare structure.Important aspects of screening include adherence,which can vary signi-ficantly across ethnic and socioeconomic groups.Basic concepts of CRC screening include pre-stratification of patients by identifying risk factors and then using fecal immunochemical test or guaiac-based fecal occult blood test and/or colono-scopy or radiologic imaging techniques.Technological capabilities for CRC scree-ning are rapidly evolving and include stool DNA test,liquid biopsy,virtual colo-nography,and the use of artificial intelligence.A CRC prevention strategy should be comprehensive and include active patient education along with targeted imple-mentation of screening.展开更多
基金Supported by Natural Science Foundation of Tianjin,No.21JCZDJC00060 and No.21JCYBJC00180Tianjin Health and Medical Science and Technology Project,No.TJWJ2023QN040National Key Research and Development Program,No.2017YFC1700606 and No.2017YFC1700604.
文摘BACKGROUND Certain subgroups are at an increased risk of false fecal immunochemical test(FIT)results;however,related studies are limited,and the available evidence is conflicting.AIM To evaluate factors associated with false-positive and false-negative FIT results.METHODS This retrospective study was based on the database of the Tianjin Colorectal Cancer Screening Program from 2012 to 2020.A total of 4129947 residents aged 40-74 years completed at least one FIT.Of these,24890 asymptomatic participants who underwent colonoscopy examinations and completed lifestyle questionnaires were included in the analysis.Multivariable logistic regression was performed to identify the factors associated with false FIT results.RESULTS Among the overall screening population,88687(2.15%)participants tested positive for FIT.The sensitivity,specificity,positive predictive value,and negative predictive value of FIT for advanced neoplasms were 58.2%,44.8%,9.7%,and 91.3%,respectively.Older age,female sex,smoking,alcohol consumption,higher body mass index,and hemorrhoids were significantly associated with increased odds of false-positive and lower odds of falsenegative FIT results.Moreover,features of high-grade dysplasia or villous for advanced adenoma and the presence of cancer were also associated with lower odds of false-negative results,while irregular exercise and diverticulum were associated with higher odds of false-positive results.CONCLUSION FIT results may be inaccurate in certain subgroups.Our results provide important evidence for further individualization of screening strategies.
文摘BACKGROUND The quantitative faecal immunochemical test for haemoglobin(FIT) has been revealed to be highly accurate for colorectal cancer(CRC) detection not only in a screening setting, but also in the assessment of patients presenting lower bowel symptoms. Therefore, the National Institute for Health and Care Excellence has recommended the adoption of FIT in primary care to guide referral for suspected CRC in low-risk symptomatic patients using a 10 μg Hb/g faeces threshold.Nevertheless, it is unknown whether FIT′s accuracy remains stable throughout the broad spectrum of possible symptoms.AIM To perform a systematic review and meta-analysis to assess FIT accuracy for CRC detection in different clinical settings.METHODS A systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2018 to conduct a meta-analysis of prospective studies including symptomatic patients that evaluated the diagnostic accuracy of quantitative FIT for CRC detection. Studies were classified on the basis of brand,threshold of faecal haemoglobin concentration for a positive test result,percentage of reported symptoms(solely symptomatic, mixed cohorts) and CRC prevalence(< 2.5%, ≥ 2.5%) to limit heterogeneity and perform subgroup analysis to assess the influence of clinical spectrum on FIT′s accuracy to detect CRC.RESULTS Fifteen cohorts including 13073 patients(CRC prevalence 0.4% to 16.8%) were identified. Pooled estimates of sensitivity for studies using OC-Sensor at 10 μg Hb/g faeces threshold(n = 10400) was 89.6% [95% confidence interval(CI): 82.7%to 94.0%). However, pooled estimates of sensitivity for studies formed solely by symptomatic patients(n = 4035) and mixed cohorts(n = 6365) were 94.1%(95%CI: 90.0% to 96.6%) and 85.5%(95%CI: 76.5% to 91.4%) respectively(P <0.01), while there were no statistically significant differences between pooled sensitivity of studies with CRC prevalence < 2.5%(84.9%, 95%CI: 73.4% to 92.0%)and ≥ 2.5%(91.7%, 95%CI: 83.3% to 96.1%)(P = 0.25). At the same threshold, OCSensor? sensitivity to rule out any significant colonic lesion was 78.6%(95%CI:75.6% to 81.4%). We found substantial heterogeneity especially when assessing specificity.CONCLUSION The results of this meta-analysis confirm that, regardless of CRC prevalence,quantitative FIT is highly sensitive for CRC detection. However, FIT ability to rule out CRC is higher in studies solely including symptomatic patients.
基金Supported by a 2-Year Research Grant of Pusan National University
文摘AIM To evaluate the efficacy of quantitative fecal immunochemical test(FIT) as biomarker of disease activity in ulcerative colitis(UC).METHODS Between February 2013 and November 2014, a total of 82 FIT results, obtained in conjunction with colonoscopies, were retrospectivelyevaluated for 63 patients with UC. The efficacy of FIT for evaluation of disease activity was compared to colonoscopic findings. Quantitative fecal blood with automated equipment examined from collected feces. Endoscopic disease severity were assessed using the Mayo endoscopic subscore(MES) classification. The extent of disease were classified by proctitis(E1), left sided colitis(E2), and extensive colitis(E3). Clinical activity were subgrouped by remission or active.RESULTS All of 21 patients with MES 0 had negative FIT(< 7 ng/mL), but 22 patients with MES 2 or 3 had a mean FIT of > 134.89 ng/m L. The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) and accuracy of negative FIT about mucosal healing were 73.33%, 81.82%, 91.49%, 51.43% and 73.17%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of predictive value of positive FIT(cutoff value > 100 ng/mL) about active disease status were 45.45%, 93.33%, 71.43%, 82.35%and 26.83%, respectively. Among patients with clinical remission, FIT was negative in 31(81.6%) of 38 cases, with a mean fecal hemoglobin concentration of 6.12 ng/mL(range, negative to 80.9 ng/mL) for this group of patients. Among patients with clinical active disease, FIT was negative in 16(36.4%) out of 44 cases, with a mean fecal hemoglobin concentration > 167.4 ng/mL for this group of patients. FIT was positively correlated with endoscopic activity(r = 0.626, P < 0.01) and clinical activity(r = 0.496, P < 0.01). But, FIT did not correlate with the extent of disease(r =-0.047, P = 0.676)CONCLUSION Quantitative FIT can be a non-invasive and effective biomarker for evaluation of clinical and endoscopic activity in UC, but not predict the extent of disease.
文摘Objective:Integration of risk stratification into fecal immunochemical test(FIT)might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer(CRC)screening.A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment(QRA)and FIT,FIT-only and QRA-only strategies in a CRC screening program in China.Methods:The study included 29,626 individuals aged 40-74 years and invited to participate in a CRC screening program in China.Participants were first invited to undertake QRA and one-time FIT(OC-sensor).Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy.Participation,detection rate,and resource demand for colonoscopy were calculated and compared.Results:Of the 29,626 invitees,20,203 completed the parallel combination,8,592 completed the QRA-only,and11 completed the FIT-only strategy.For the parallel combination,FIT-only,and QRA-only strategies,the overall positivity rates were 10.2%(2,928/28,806),5.4%(1,096/20,214),and 6.8%(1,944/28,795),respectively;the yield of advanced neoplasm per 10,000 invitees were 46.9[95%confidence interval(95%CI):39.8-55.4],36.8(95%CI:30.5-44.4),and 12.2(95%CI:8.8-16.8),respectively;the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7%(95%CI:4.0%-5.6%),9.9%(95%CI:8.3%-11.9%),and 1.9%(95%CI:1.3%-2.6%),respectively;the number of colonoscopies required to detect one advanced neoplasm was 11.4(95%CI:9.8-13.4),5.7(95%CI:4.8-6.7),and 28.4(95%CI:20.7-39.2),respectively.Conclusions:The parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.
基金Supported by Spain’s Carlos III Health Care Institute by Means of Project(Co-funded by European Regional Development Fund/European Social Fund"A way to make Europe"/"Investing in your future"),No.PI17/00837。
文摘Faecal immunochemical tests(FITs)are the most widely colorectal cancer(CRC)diagnostic biomarker available.Many population screening programmes are based on this biomarker,with the goal of reducing CRC mortality.Moreover,in recent years,a large amount of evidence has been produced on the use of FIT to detect CRC in patients with abdominal symptoms in primary healthcare as well as in surveillance after adenoma resection.The aim of this review is to highlight the available evidence on these two topics.We will summarize the evidence on diagnostic yield in symptomatic patients with CRC and significant colonic lesion and the different options to use this(thresholds,brands,number of determinations,prediction models and combinations).We will include recommendations on FIT strategies in primary healthcare proposed by regulatory bodies and scientific societies and their potential effects on healthcare resources and CRC prognosis.Finally,we will show information regarding FIT-based surveillance as an alternative to endoscopic surveillance after high-risk polyp resection.To conclude,due to the coronavirus disease 2019 pandemic,FIT-based strategies have become extremely relevant since they enable a reduction of colonoscopy demand and access to the healthcare system by selecting individuals with the highest risk of CRC.
文摘AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results.RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.
文摘AIM:To examine the feasibility of predicting the flareup of ulcerative colitis (UC) before symptoms emerge using the immunochemical fecal occult blood test (IFOBT).METHODS:We prospectively measured fecal hemoglobin concentrations in 78 UC patients using the I-FOBT every 1 or 2 mo.RESULTS:During a 20 mo-period,823 fecal samples from 78 patients were submitted.The median concentration of fecal hemoglobin was 41 ng/mL (range:0-392 500 ng/mL).There were three types of patients with regard to the correlation between I-FOBT and patient symptoms;the synchronous transition type with symptoms (44 patients),the unrelated type withsymptoms (19 patients),and the flare-up predictive type (15 patients).In patients with the flare-up predictive type,the values of I-FOBT were generally low during the study period with stable symptoms.Two to four weeks before the flare-up of symptoms,the I-FOBT values were high.Thus,in these patients,I-FOBT could predict the flare-up before symptoms emerged.CONCLUSION:Flare-up could be predicted by I-FOBT in approximately 20% of UC patients.These results warrant periodical I-FOBT in UC patients.
基金Supported by Instituto de Salud Carlos III through the project PI17/00837(Co-funded by European Regional Development Fund/European Social Fund"A way to make Europe"/"Investing in your future")
文摘BACKGROUND Faecal immunochemical test(FIT)has been recommended to assess symptomatic patients for colorectal cancer(CRC)detection.Nevertheless,some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized.A positive FIT result could be related to other gastrointestinal cancers(GIC).AIM To assess the risk of GIC detection and related death in FIT-positive symptomatic patients(threshold 10μg Hb/g faeces)without CRC.METHODS Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection.Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare,underwent a quantitative FIT before undergoing a complete colonoscopy.Patients without CRC were divided into two groups(positive and negative FIT)using the threshold of 10μg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research.We determined the cumulative risk of GIC,CRC and upper GIC.Hazard rate(HR)was calculated adjusted by age,sex and presence of significant colonic lesion.RESULTS We included 2709 patients without CRC and a complete baseline colonoscopy,730(26.9%)with FIT≥10μgr Hb/gr.During a mean time of 45.5±20.0 mo,a GIC was detected in 57(2.1%)patients:An upper GIC in 35(1.3%)and a CRC in 14(0.5%).Thirty-six patients(1.3%)died due to GIC:22(0.8%)due to an upper GIC and 9(0.3%)due to CRC.FIT-positive subjects showed a higher CRC risk(HR 3.8,95%CI:1.2-11.9)with no differences in GIC(HR 1.5,95%CI:0.8-2.7)or upper GIC risk(HR 1.0,95%CI:0.5-2.2).Patients with a positive FIT had only an increased risk of CRC-related death(HR 10.8,95%CI:2.1-57.1)and GIC-related death(HR 2.2,95%CI:1.1-4.3),with no differences in upper GIC-related death(HR 1.4,95%CI:0.6-3.3).An upper GIC was detected in 22(0.8%)patients during the first year.Two variables were independently associated:anaemia(OR 5.6,95%CI:2.2-13.9)and age≥70 years(OR 2.7,95%CI:1.1-7.0).CONCLUSION Symptomatic patients without CRC have a moderate risk increase in upper GIC,regardless of the FIT result.Patients with a positive FIT have an increased risk of post-colonoscopy CRC.
文摘AIM: To measure the compliance of an Academic Hospital staff with a colorectal cancer(CRC) screening program using fecal immunochemical test(FIT).METHODS: All employees of 'Attikon' University General Hospital aged over 50 years were thoroughly informed by a team of physicians and medical students about the study aims and they were invited to undergo CRC screening using two rounds of FIT(DyoniFOB~ Combo H, DyonMed SA, Athens, Greece). The tests were provided for free and subjects tested positive were subsequently referred for colonoscopy. One year after completing the two rounds, participants were asked to be re-screened by means of the same test.RESULTS: Among our target population consisted of 211 employees, 59(27.9%) consented to participate, but only 41(19.4%) and 24(11.4%) completed the first and the second FIT round, respectively. Female gender was significantly associated with higher initial participation(P = 0.005) and test completion- first and second round-(P = 0.004 and P = 0.05) rates, respectively. Phy sician’s(13.5% vs 70.2%, P < 0.0001) participation and test completion rates(7.5% vs 57.6%, P < 0.0001 for the first and 2.3% vs 34%, P < 0.0001 for the second round) were significantly lower compared to those of the administrative/technical staff. Similarly, nurses participated(25.8% vs 70.2%, P = 0.0002) and completed the first test round(19.3% vs 57.6%, P = 0.004) in a significant lower rate than the administrative/technical staff. One test proved false positive. No participant repeated the test one year later.CONCLUSION: Despite the well-organized, guided and supervised provision of the service, the compliance of the Academic Hospital personnel with a FIT-based CRC screening program was suboptimal, especially among physicians.
文摘The anti-chlorpyrifos polyclonal antibodies were obtained by using the artificial immuneantigen to immune in New Zealands white rabbits. The enzyme-tagged antibodies wereprepared by coupling horseradish peroxidase (HRP) to the purified antibody with themodified sodium periodate method. The indirect competitive enzyme linked immuno-sorbentassays (ELISA) and the HRP-tagged antibody direct ELISA (E-Ab) were established, respectively.The limit of detection (LOD) for the indirect ELISA and E-Ab were 0.0033 and 0.0042 gmL-1, respectively. The linear detection ranged well from 0.005 to 2.0 g mL-1.
文摘Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistochemical technique. The trace P-450HSj isozyme (Mr. 51.5 Kd) was found in human gastric mucosa. It was similar to P-450j in molecular weight, catalytic and immunochemical properties. The concentrations of P-450HSj in mucosa of lesser curvature were higher than those in greater curvature. This might be one of the important reasons that lesser curvature is the commonest area for gastric carcinoma. But there was possibly less P-450HSj in gastric mucosa with cancer. Im-munohistochemically, P-450HSj was discovered in the cytoplasm of some glandular epithelial cells, especially in the glands with hyperplastic and intestinal metaplastic changes adjacent to carcinoma. It was also found in some normal glands and in tumor cells of high-differentiated adenocarcinoma, but not in those of low-differentiated ones. Following subjects are discussed: (1) the method of detecting trace P-450HSj, (2) the rule of distribution of P-450HSj, and (3) the relationship between the isozyme and the occurrence of gastric cancer caused by nitrosa-mines.
基金Supported by Foundation of Population Screening Mid-West Netherlands,Amsterdam,The Netherlands(BoMW)Foundation of Population Screening South-West Netherlands,Rotterdam,The Netherlands(BoZW)+2 种基金Netherlands Comprehensive Cancer Organization(IKNL)Netherlands Organization for Health Research and Development of the Dutch Ministry of Health(ZonMW)PALGA,the Nationwide Network and Registry of Histo-and Cytopathology in the Netherlands.
文摘BACKGROUND For optimizing fecal immunochemical test(FIT)-based screening programs,reducing the rate of missed colorectal cancers(CRCs)by FIT(FIT-interval CRCs)is an important aspect.Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all(precursor)lesions.AIM To compare the molecular make-up of FIT-interval CRCs to lesions that are detected by FIT[screen-detected CRCs(SD-CRCs)].METHODS FIT-interval CRCs observed in a Dutch pilot-program of FIT-based screening were compared to a control group of SD-CRCs in a 1:2 ratio,resulting in 27 FIT-interval CRC and 54 SD-CRCs.Molecular analyses included microsatellite instability(MSI),CpG island methylator phenotype(CIMP),DNA sequence mutations and copy number alterations(CNAs).RESULTS Although no significant differences were reached,FIT-interval CRCs were more often CIMP positive and MSI positive(33%CIMP in FIT-interval CRCs vs 21%in SD-CRCs(P=0.274);19%MSI in FIT-interval CRCs vs 12%in SD-CRCs(P=0.469)),and showed more often serrated pathway associated features such as BRAF(30%vs 12%,P=0.090)and PTEN(15%vs 2.4%,P=0.063)mutations.APC mutations,a classic feature of the adenoma-carcinoma-sequence,were more abundant in SD-CRCs(68%vs 40%in FIT-interval CRCs P=0.035).Regarding CNAs differences between the two groups;FIT-interval CRCs less often showed gains at the regions 8p11.22-q24.3(P=0.009),and more often gains at 20p13-p12.1(P=0.039).CONCLUSION Serrated pathway associated molecular features seem to be more common in FIT-interval CRCs,while classic adenoma carcinoma pathway associated molecular features seem to be more common in SD-CRCs.This indicates that proximal serrated lesions may be overrepresented among FITinterval CRCs.
基金Supported by the Innovation Platform for Academicians of Hainan Province,No.2022136the Specific Research Fund of the Innovation Platform for Academicians of Hainan Province,No.YSPTZX202313+2 种基金Hainan Province Clinical Medical Center,No.2021818Hainan Provincial Health Industry Research Project,No.22A200078National Clinical Key Specialty Capacity Building Project,China,No.202330.
文摘BACKGROUND The incidence of colorectal cancer(CRC)in China is steadily rising,with a high proportion of advanced-stage diagnoses.This highlights the significance of early detection and prevention measures to enhance survival rates.Fecal immunochemical testing(FIT)is a globally recommended CRC screening method;however,limited research has been conducted on its application in Hainan.AIM To assess the efficacy and adherence of FIT screening among average-risk individuals in Hainan,while also examining the risk factors associated with positive FIT results.METHODS This population-based cross-sectional study implemented FIT screening for CRC in 2000 asymptomatic participants aged 40-75 years from five cities and 21 community health centers in Hainan Province.The study was conducted from August 2022 to April 2023,employing a stratified sampling method to select participants.Individuals with positive FIT results subsequently underwent colonoscopy.Positive predictive values for confirmed CRC and advanced adenoma were calculated,and the relationship between relevant variables and positive FIT results was analyzed usingχ2 tests and multivariate logistic regression.RESULTS A total of 1788 participants completed the FIT screening,with a median age of 57 years(interquartile range:40-75).Among them,503(28.1%)were males,and 1285(71.9%)were females,resulting in an 89.4%compliance rate for FIT screening.The overall positivity rate of FIT was 4.4%[79 out of 1788;95%confidence interval(CI):3%-5%].The specific positivity rates for Haikou,Sanya,Orient City,Qionghai City,and Wuzhishan City were 9.6%(45 of 468;95%CI:8%-11%),1.3%(6 of 445;95%CI:0.1%-3.1%),2.7%(8 of 293;95%CI:1.2%-4.3%),3.3%(9 of 276;95%CI:1.0%-6.3%),and 4.2%(11 of 406;95%CI:1.2%-7.3%),respectively.Significant associations were found between age,dietary habits,and positive FIT results.Out of the 79 participants with positive FIT results,55 underwent colonoscopy,demonstrating an 82.2%compliance rate.Among them,10 had a clean gastrointestinal tract,43 had polyps or adenomas,and 2 were confirmed to have CRC,yielding a positive predictive value of 3.6%(95%CI:0.9%-4.2%).Among the 43 participants with polyps or adenomas,8 were diagnosed with advanced adenomas,resulting in an advanced adenoma rate of 14.5%(95%CI:10.1%-17.7%).CONCLUSION In the Hainan region,FIT screening for CRC among asymptomatic individuals at average risk is feasible and wellreceived.
文摘Metallothioneins in Caenorhahditis elegans (CeMT-Ⅰ and Ⅱ) were punned by the combination of gel filtration ion-exchange chromatography.and high-performance liquid chromatography.Amino acid compositions and amino-terminal sequences of CeMT-Ⅰ and Ⅱ were slightly different from those of vertebrate MTs previously reported, although cysteine residue contents were relatively high.Enzyme immunoassay using anti-CeMT-Ⅱ antibody showed the difference of antigenicity to rat MT-Ⅰ and Ⅱ and even to CeMT-Ⅰ. Immunohistochemical staining revealed the existence of CeMT-Ⅱ in the intestine and the eggs, suggesting the role of MT in detoxification and homeostasis of heavv metals. 1990 Academic Press.Inc.
文摘The formation of covalent adducts as a result of the interaction of metabolically activated chemicals with host macromolecules is a common critical event in mutagenic, carcinogenic, and immunologic phenomena. Because of their antigenicity and their immunogenicity, covalent adducts may be detected using sensitive immunochemical techniques. The immunochemical approaches to biomonitoring and molecular dosimetry of DNA damage are particularly attractive because they allow sensitive quantitation of specific DNA adducts present in small samples and do not rely on the use of radiolabeled adducts. Two examples of biomarker immunoassay development are presented: an avidin/biotin-amplified ELISA for the major DNA adduct of the human bladder carcinogen 4-aminobiphenyl (ABP), and a particle concentration fluorescent immunoassay (PCFIA) for the major protein adduct associated with toxicity by the prototype hepatotoxin acetaminophen. The examples illustrate critical steps in the development of biomarker immunoassays which include selection of the relevant adduct, preparation of an appropriate immunogen, immunization, characterization of antisera, and development of application-specific sample processing techniques for biomarker quantitation. Immunochemical procedures may be combined with other analytical techniques to form hybrid systems which take advantage of both the antigenicity and the physical or chemical properties of a biomarker to achieve greater specificity and/or sensitivity. The future usefulness of these new tools of molecular epidemiology will depend on a compound-by-compound validation of methods and critical evaluation of the biologic importance of the particular antigenic biomarker as an indicator of exposure and as an indicator of risk.
基金Supported by A Research Grant of Center for Translational Molecular Medicine, The Netherlands, to van Turenhout STGrant of Nycomed B.V., Hoofddorp to "the Amsterdam Gut-club", The Netherlands+1 种基金The Netherlands Organization for Health Research and Development, ZonMW, No. 50-50115-98-060,project 63000004The original trial was registered under IS-RCTN57917442 at Current Controlled Trials (www.controlled-trials.com)
文摘AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.
文摘Screening for colorectal cancer(CRC)has the potential to strongly reduce incidence and mortality of this common cancer[1,2].While fecal tests have long been established as non-invasive CRC screening tests,an intensive search for blood-based tests,which have been claimed to be easier to integrate into routine medical practice,is underway[3,4].Most recently,clinical validation of a circulating tumor DNA-based blood test for the detection of patterns of CpG(cytosine followed by guanine)dinucleotidemethylation has been reported from the PREEMPT CRC study,a large,United States(US)based screening study including 27,010 participants of screening colonoscopy[4].The study was sponsored by the manufacturer and reported with limited details about the laboratory analyses.With a sensitivity of 79.2%(95%confidence interval[CI],68.4%-86.9%)for CRC detection and a specificity of 91.5%(95%CI,91.2%-91.9%)for advanced colorectal neoplasia,the test met the pre-specified acceptance criteria,but the sensitivity for detecting advanced precancerous lesions(APCL)was low(12.5%).We aimed to compare the reported diagnostic performance of this blood-based test with that of the fecal immunochemical test(FIT),the best established and globally most widely used non-invasive CRC test[5],in a large population of screening colonoscopy participants from Germany.
基金by grants from the Cancer Foundation of Chinathe Beijing Nova Program of Science and Technology(No.Z191100001119065)+1 种基金the Natural Science Foundation of Beijing Municipality(No.7202169)the CAMS Innovation Fund for Medical Sciences(No.2017-I2M-1-006).
文摘Background:Fecal immunochemical tests(FITs)are the most widely used non-invasive tests in colorectal cancer(CRC)screening.However,evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse.Methods:Based on a CRC screening trial(TARGET-C),we included 3144 pre-colonoscopy fecal samples,including 24 CRCs,230 advanced adenomas,622 non-advanced adenomas,and 2268 participants without significant findings at colonoscopy.Three selfadministered qualitative FITs(Pupu tube)with positivity thresholds of 8.0,14.4,or 20.8 mg hemoglobin(Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT(OC-Sensor)with a positivity threshold of 20 mg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory.The diagnostic performance of the FITs for detecting colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds(for the quantitative FIT).Results:At the thresholds preset by the manufacturers,apart from the qualitative FIT-3,significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1(33.9%[95%CI:28.7–39.4%])and qualitative FIT-2(22.2%[95%CI:17.7–27.2%])compared to the quantitative FIT(11.7%[95%CI:8.4–15.8%]),while at a cost of significantly lower specificities.However,such difference was not observed for detecting CRC.For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly,there were no significant differences in terms of sensitivity,specificity,positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs,which was further evidenced in ROC analysis.Conclusions:Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the positivity thresholds preset by the manufacturer,such heterogeneity could be overcome by adjusting thresholds to yield comparable specificities or positivity rates.Future CRC screening programs should select appropriate types of FITs and define the thresholds based on the targeted specificities and manageable positivity rates.
基金supported by Guangzhou Science and Technology Plan Projects(Health Medical Collaborative Innovation Program of Guangzhougrant No 201400000001-4)Science and Technology Planning Project of Guangdong Province(No 2013B0218001462).
文摘Objective:To explore the performance of a protocol combining fecal immunochemical test(FIT)and a high-risk factor questionnaire(HRFQ)for selecting patients requiring colonoscopy as part of a population-based colorectal cancer(CRC)screening program in China.Methods:From 2015 to 2016,we conducted a CRC screening program for all residents aged 45 years or older in Tianhe District,Guangzhou City,China.Participants underwent an FIT and received an HRFQ as part of primary screening.Those with positive FIT and/or HRFQ results were considered to be at high risk and were recommended to undergo colonoscopy.Results:A total of 10074 subjects were recruited and enrolled in the screening program.In the enrolled population,17.5%had positive FIT results and 19.4%had positive HRFQ results.Of those recommended to undergo diagnostic colonoscopy,773 did so.The screening method’s overall positive predictive value(PPV)was 4.9%for non-adenomatous polyps,11.4%for low-risk adenomas(LRAs),15.9%for high-risk adenomas(HRAs)and 1.6%for CRC.The PPVs of positive FIT results for nonadenomatous polyps,LRAs,HRAs and CRC were 5.2%,15.9%,22.5%and 2.5%,respectively.The PPVs of positive HRFQ results for non-adenomatous polyps,LRA,HRA and CRC were 4.1%,10.2%,14.3%and 1.4%,respectively.The PPVs associated with combined positive FIT and HRFQ results for non-adenomatous polyps,LRAs,HRAs and CRC were 4.5%,16.4%,23.7%and 2.8%,respectively.Conclusion:Our results suggest that this two-step CRC screening strategy,involving a combination of FIT and HRFQ followed by colonoscopy,is useful to identify early-stage CRC.The high detection rates and PPVs for CRC and adenomas encourage this strategy’s use in ongoing screening programs.
文摘Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco smoking,alco-hol consumption,and unhealthy diet.CRC screening methods vary considerably between countries and depend on incidence,economic resources and healthcare structure.Important aspects of screening include adherence,which can vary signi-ficantly across ethnic and socioeconomic groups.Basic concepts of CRC screening include pre-stratification of patients by identifying risk factors and then using fecal immunochemical test or guaiac-based fecal occult blood test and/or colono-scopy or radiologic imaging techniques.Technological capabilities for CRC scree-ning are rapidly evolving and include stool DNA test,liquid biopsy,virtual colo-nography,and the use of artificial intelligence.A CRC prevention strategy should be comprehensive and include active patient education along with targeted imple-mentation of screening.
