Drug-induced Liver Injury Associated with Antinuclear Antibodies

Abstract

Objective. Colorectal cancer (CRC) screening programs can decide upon the type of fecal occult blood test (FOBT): the guaiac FOBT (g-FOBT) or the immunological FOBT (i-FOBT). The effectiveness of any screening program depends not only on the diagnostic performance of the screening test but also on the compliance and general acceptance of the test by the public. Any decision on the type of FOBT for CRC screening should also take acceptation and perception into account. The aim of the present study was to study differences in patient perception between i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups in a population based study. Material and methods. Differences in patient perception of i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups were investigated (n = 20,623) by sending a short questionnaire to all invited to the first Dutch CRC screening trial. Results. i-FOBT was perceived significantly more favorable than g-FOBT. About 1275 (32%) participants reported the g-FOBT not easy to use, not easy to perform, disgusting or shameful compared to 742 (16%) for the i-FOBT (p < 0.001). The participation rate was significantly higher in those who received i-FOBT compared to the g-FOBT group: 6159 of 10,322 (60%) versus 4839 of 10,301 (47%) (p < 0.001). Conclusions. These findings support the selection of i-FOBT as the more appropriate test for population screening programs.     

Short term outcomes of the first round of a pilot colorectal cancer screening programme with guaiac based faecal occult blood test

Objective

To assess both feasibility and short term outcomes of a population based colorectal cancer screening programme using a biennial guaiac based faecal occult blood test (gFOBT).

Method

All participants were invited by mail to take part in a screening programme using a non‐rehydrated gFOBT. The gFOBTs were first provided by general practitioners (GPs) and then directly mailed to individuals who failed to comply after two invitations. The setting was a French administrative district: Haut‐Rhin (710 000 inhabitants). 182 981 residents aged 50–74 years were invited to participate.

Results

19 274 people (10.5%) were excluded from gFOBT screening and 90 706 completed a gFOBT, so that the participation rate was 55.4% of those eligible. 76.5% of the completed gFOBTs were provided by GPs and 15.5% by direct mailing. The gFOBT positivity rate was 3.4%. The positive predictive value was 42.7% for neoplasia (women 30.8%, men 52.5%), 23.6% for advanced adenoma, and 7.6% for cancer. The number of normal colonoscopic procedures (without neoplasia) needed to be performed for each colonoscopy detecting an advanced neoplasia was 1.8, lower in men (1.2) than in women (3.4), and decreasing with age. Detection rates for neoplasia and cancer were 12.8 and 2.3 per 1000 people screened. 206 adenocarcinomas were detected: 47.6% were stage I and 23.8% stage II. The direct cost was estimated at €29.3 per screened person and €13 466 per cancer detected.

Conclusions

Participation and diagnostic yield of controlled trials of gFOBT screening are reproducible in the real world at an acceptable cost through an organised population based programme involving GPs.     

Impact of colorectal cancer screening participation in remote northern Canada: A retrospective cohort study

BACKGROUNDScreening provides earlier colorectal cancer (CRC) detection and improves outcomes. It remains poorly understood if these benefits are realized with screening guidelines in remote northern populations of Canada where CRC rates are nearly twice the national average and access to colonoscopy is limited.AIMTo evaluate the participation and impact of CRC screening guidelines in a remote northern population.METHODSThis retrospective cohort study included residents of the Northwest Territories, a northern region of Canada, age 50-74 who underwent CRC screening by a fecal immunohistochemical test (FIT) between January 1, 2014 to March 30, 2019. To assess impact, individuals with a screen-detected CRC were compared to clinically-detected CRC cases for stage and location of CRC between 2014-2016. To assess participation, we conducted subgroup analyses of FIT positive individuals exploring the relationships between signs and symptoms of CRC at the time of screening, wait-times for colonoscopy, and screening outcomes. Two sample Welch t-test was used for normally distributed continuous variables, Mann-Whitney-Wilcoxon Tests for data without normal distribution, and Chi-square goodness of fit test for categorical variables. A P value of < 0.05 was considered to be statistically significant.RESULTS6817 fecal tests were completed, meaning an annual average screening rate of 25.04%, 843 (12.37%) were positive, 629 individuals underwent a follow-up colonoscopy, of which, 24.48% had advanced neoplasia (AN), 5.41% had CRC. There were no significant differences in stage, pathology, or location between screen-detected cancers and clinically-detected cancers. In assessing participation and screening outcomes, we observed 49.51% of individuals referred for colonoscopy after FIT were ineligible for CRC screening, most often due to signs and symptoms of CRC. Individuals were more likely to have AN if they had signs and symptoms of cancer at the time of screening, waited over 180 d for colonoscopy, or were indigenous [respectively, estimated RR 1.18 95%CI of RR (0.89-1.59)]; RR 1.523 (CI: 1.035, 2.240); RR 1.722 (CI: 1.165, 2.547)].CONCLUSIONScreening did not facilitate early cancer detection but facilitated higher than anticipated AN detection. Signs and symptoms of CRC at screening, and long colonoscopy wait-times appear contributory.     

Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening

Colorectal cancer (CRC) is the second most common cause of cancer deaths in Canadian men and women - accounting for almost 12% of all cancer deaths. In Ontario, it is estimated that 8100 persons were diagnosed with CRC in 2011, and 3250 died from the disease. CRC incidence and mortality rates in Ontario are among the highest in the world. Screening offers the best opportunity to reduce this burden of disease. The present report describes the findings and recommendations of Cancer Care Ontario's Fecal Immunochemical Tests (FIT) Guidelines Expert Panel, which was convened in September 2010 by the Program in Evidence-Based Care. The purpose of the present guideline is to evaluate the existing evidence concerning FIT to inform the decision on how to replace the current guaiac fecal occult blood test with FIT in the Ontario ColonCancerCheck Program. Eleven articles were included in the present guideline, comprising two systematic reviews, five articles reporting on three randomized controlled trials, and reports of four other studies. Additionally, one laboratory study was obtained that reported on several parameters of FIT tests that helped to inform the present recommendation. The performance of FIT is superior to the standard guaiac fecal occult blood test in terms of screening participation rates and the detection of CRC and advanced adenoma. Given greater specimen instability with the use of FIT, a pilot study should be undertaken to determine how to implement the FIT in Ontario.     

Diagnostic Yield in a Biennial Hemoccult-II Screening Program Compared to a Once-only Screening with Flexible Sigmoidoscopy and Hemoccult-II

Background: Flexible sigmoidoscopy (FS) has a higher degree of sensitivity for detecting colorectal neoplasia in the left side of the colon than Hemoccult-II (H-II). However, no randomized controlled trial has compared a single FS screening with H-II screening program (annual or biennial) despite with well-documented mortality reduction from colorectal cancer (CRC) in the latter. The aim was to compare the diagnostic yield of colorectal neoplasia in two aged-matched groups from two different randomized screening trials; one group screened by a single FS+H-II, the other with biennial H-II over the course of 16 years. Methods: 24,465 persons invited to participate in the Funen biennal H-II screening program were compared with 4,460 similar persons invited to another Funen trial using a single FS+H-II. Results: Compliance in the biennial H-II program was 65.5% during the first screening round compared to 39.8% for FS+H-II. The cumulative number of persons with positive tests was 8.2% (positive H-II) in the biennial H-II program during 16 years and 20.3% (polyps > 3 mm in diameter seen at FS or positive H-II) for once-only FS+H-II. The diagnostic yield of CRC per 1,000 screened was 9.9 in the biennial H-II program and 6.6 after FS+H-II (6.5 and 2.7 per 1,000 invited). The yield of advanced adenomas (≥ 10 mm and/or villous structure and/or severe dysplasia) was 2.3% in the H-II program and 3.3% after FS+H-II among the screened persons, but this difference disappeared when persons invited, but not necessarily screened, were compared (1.5% versus 1.3%). Conclusion: Screening with H-II in a biennial screening program during 16 years detected more CRCs than a single screening with FS+H-II and a similar number of advanced adenomas.     

Comparison of immunochemical and guaiac-based fecal occult blood test in screening and surveillance for advanced colorectal neoplasms: A meta-analysis

OBJECTIVE: To systematically evaluate whether immunochemical fecal occult blood tests (iFOBT) could improve clinical performance and test accuracy in screening and surveillance for advanced colorectal neoplasms. METHODS: Eligible articles were identified by searches of electronic databases. All randomized trials and diagnostic cohort trials directly comparing iFOBT with guaiac-based FOBT (gFOBT) were included. A statistical analysis was performed using RevMan 4.2.8. A sensitivity, specificity and summary receiver operating characteristic curve was performed using Meta Disc. RESULTS: We identified five randomized trials and 11 diagnostic cohort trials. In the randomized trials, the detection rates of advanced colorectal neoplasms with iFOBT or gFOBT were 2.23 percent and 1.24 percent, respectively. The pooled odds ratio (OR) was 1.50 (95% CI 0.94–2.39). In cohort trials, the advanced neoplasm detection rates of iFOBT or gFOBT were 1.44 percent and 0.50 percent (OR 1.99, 95% CI 1.24–3.19) in the average-risk screened population, and were 8.8 percent and 7.1 percent (OR 1.27, 95% CI 1.01–1.60) in diagnosed patients scheduled for colonoscopy. The sensitivity of iFOBT (0.67, 95% CI 0.61–0.73) was superior to that of gFOBT (0.54, 95% CI 0.48–0.60), as well as the specificities (0.85, 95% CI 0.83–0.87 vs 0.80, 95% CI 0.78–0.82) and positive predictive values (0.41 vs 0.29) in cohort trials of diagnosed patients. CONCLUSION: Our review suggests that iFOBT could perform better in increasing the detection rate of advanced colorectal neoplasm than gFOBT and possesses higher sensitivity and specificity in the surveillance of advanced colorectal neoplasm for patients.     

Diagnosing colorectal cancer and inflammatory bowel disease in primary care: The usefulness of tests for faecal haemoglobin,faecal calprotectin,anaemia and iron deficiency. A prospective study

Objective: Abdominal complaints are common reasons to consult primary care but they are seldom caused by colorectal cancer (CRC), high-risk adenomas (HRAs), or inflammatory bowel disease (IBD). Reliable diagnostic aids would be helpful in deciding which patients to refer for bowel imaging. Our aim was to assess the value of a faecal immunochemical test (FIT) and a faecal calprotectin (FC) test in detecting CRC, HRAs and IBD in primary care, and the value of combining these tests with anaemia and iron-deficiency tests.

Materials and methods: This prospective study included 373 consecutive patients that received a FIT or a FC test ordered by a primary care physician. We collected samples for FITs, FC tests, full blood counts and iron-deficiency tests. Physicians were instructed to refer patients with a positive FIT or FC test (cut-off ≥100μg/g) for bowel imaging. The patients’ presenting symptoms were recorded. Patients were followed for 2 years.

Results: The best test for detecting CRC and IBD was the combination of the FIT and haemoglobin concentration. This test had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 61.7%, 11.7% and 100%, respectively. The FIT detected a significantly larger proportion of CRC, HRAs and IBD than the FC test (0.92 versus 0.46, 95% confidence interval 0.22–0.67).

Conclusion: A negative FIT combined with a normal haemoglobin concentration could rule out CRC and IBD with a high degree of safety. This could be useful in prioritising referrals for bowel imaging from primary care.     

Diagnostic accuracy of one or two faecal haemoglobin and calprotectin measurements in patients with suspected colorectal cancer

Background: The role of faecal biomarkers in patients at ‘high risk’ of colorectal cancer (CRC) is not yet defined. Pre-analytical factors, such as heterogeneity of biomarker distribution within faeces, may influence their optimisation in clinical practice. We undertook to determine whether repeat or combined biomarker testing improves diagnostic accuracy for CRC or clinically significant disease.

Methods: Patients referred with suspected CRC provided two separate faecal samples each for faecal immunochemical testing (FIT) and faecal calprotectin (FC) prior to investigation. Diagnostic accuracy of FIT and FC were evaluated based on final diagnoses.

Results: Five hundred fifteen patients completed a full colorectal evaluation. The optimal cut-off for CRC using a single FIT was ≥12 µgHb/g faeces (84.6% sensitivity, 88.5% specificity). For two FIT, the cut-off was ≥43 µgHb/g faeces if either and ≥2 µgHb/g faeces if both were positive. There was no advantage in their diagnostic accuracy compared with a single FIT. FC had a lower diagnostic accuracy for CRC than FIT, which was not improved by repeat FC. No benefit was identified with FIT-FC combined.

For CRC, significant adenomatous polyps and organic enteric disease combined, FIT and FC performed similarly to each other but were poorer predictors (AUC 0.677 and 0.660). There was no uplift in diagnostic accuracy when the tests were repeated or combined.

Conclusion: This study supports using a single FIT at a cut-off close to that recommended by NICE DG30 to improve diagnostic accuracy for ‘two-week wait’ patients referred with suspected CRC.     

Positive predictive value of fecal immunochemical test for high-risk colonic adenomas and carcinoma: A health maintenance organization cohort screening study in Lebanon

Background and Study AimsFecal Immunochemical Test (FIT) is one of the leading modalities for colorectal cancer screening. Studies show that FIT is highly sensitive for the detection of colorectal cancer (CRC) but not similarly accurate for detection of pre-cancerous advanced adenomas (AA). We studied the performance metrics of FIT for the detection of CRC and AA in a health maintenance organization (HMO) cohort screening program.Patients and MethodsRetrospective cohort study of asymptomatic persons of screening age belonging to a HMO. Endoscopy and pathology reports of those who tested positive were used to calculate the positive predictive value (PPV) of FIT, and characterize endoscopic findings on colonoscopy.ResultsBetween 1995 and 2017, 3000 persons had screening fecal occult testing as part of their Employee Health Care plan. Of those, 150 had a positive qualitative FIT (cutoff 10 Âµg hemoglobin/g feces). All underwent colonoscopy, and median time to colonoscopy was 27 days. 4 (2.6%) had carcinoma (2 stage IIIA and 2 stage IIIB), 106 (70.6%) had adenomas of which 40 (26.6% of the total cohort) had advanced adenomas (≥1 cm, villous features, or high-grade dysplasia) giving a PPV for AA and carcinoma of 29% and 3% respectively. When stratified by age, the PPV of AA; carcinoma was [50–59 (21.7%; 0.0%)], [60–69 (14.6%; 4.2%)], [70–79 (42.6%; 2.1%)], [80–89 (33.3%; 11.1%)].ConclusionThe performance characteristics of FIT testing are acceptable for population screening in resource-limited settings. The results of this study are helpful when discussing expectations prior to colonoscopy in people with positive FIT.     

Familial colorectal cancer screening: When and what to do?

Colorectal cancer(CRC) is the third leading cause of death worldwide and represents a clinical challenge.Family members of patients affected by CRC have an increased risk of CRC development.In these individuals,screening is strongly recommended and should be started earlier than in the population with average risk,in order to detect neoplastic precursors,such as adenoma,advanced adenoma,and nonpolypoid adenomatous lesions of the colon.Fecal occult blood test(FOBT) is a non invasive,widespread screening method that can reduce CRC-related mortality.Sigmoidoscopy,alone or in addition to FOBT,represents another screening strategy that reduces CRC mortality.Colonoscopy is the best choice for screening highrisk populations,as it allows simultaneous detection and removal of preneoplastic lesions.The choice of test depends on local health policy and varies among countries.     

Colorectal cancer screening:20 years of development and recent progress

Colorectal cancer(CRC)is the second most common cancer in Europe and its incidence is steadily increasing.This trend could be reversed through timely secondary prevention(screening).In the last twenty years,CRC screening programs across Europe have experienced considerable improvements(fecal occult blood testing;transition from opportunistic to population based program settings).The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates.Each year,approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy.Twenty years ago,the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000.Originally,this program was based on the guaiac fecal occult blood test(FOBT)offered by general practitioners,followed by colonoscopy in cases of FOBT positivity.The program has continuously evolved,namely with the implementation of immunochemical FOBTs and screening colonoscopy,as well as the involvement of gynecologists.Since the establishment of the Czech CRC Screening Registry in 2006,2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program.The overall program expanded to cover 25.0%of the target population by 2011.However,stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation,which is currently being prepared.     

A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population

BACKGROUND & AIMS: The fecal occult blood test (FOBT) is recommended as a screening test for colorectal cancer, but there are few reliable studies on the accuracy of immunochemical FOBT. The aim of this study was to analyze the sensitivity of immunochemical FOBT and to compare the results with the findings from complete colonoscopy. METHODS: Asymptomatic adults underwent 1-time immunochemical FOBT and total colonoscopy simultaneously. The prevalence and location of colorectal neoplasia were determined by colonoscopy. The results of immunochemical FOBT and the colonoscopic findings were compared. RESULTS: Of 21,805 patients, immunochemical FOBT was positive in 1231 cases (5.6%). The sensitivity of 1-time immunochemical FOBT for detecting advanced neoplasia and invasive cancer was 27.1% and 65.8%, respectively. In addition, the sensitivity for invasive cancer according to Dukes' stage showed 50.0% for Dukes' stage A, 70.0% for Dukes' stage B, and 78.3% for Dukes' stages C or D. The sensitivity for detecting advanced neoplasia at the proximal colon was significantly lower than that detected in the distal colon (16.3% vs 30.7%, P = .00007). CONCLUSIONS: Although the screening of asymptomatic patients with immunochemical FOBT can identify patients with colorectal neoplasia to a certain extent, the sensitivity is relatively low and different according to the tumor location. Therefore, programmatic and repeated screening by immunochemical FOBT may be necessary to increase sensitivity for colorectal cancer detection.     

Fecal immunological blood test is more appealing than the guaiac-based test for colorectal cancer screening

BackgroundThe reasons for participation in fecal immunological testing (FIT) of subjects who were previously non-respondents to guaiac fecal occult blood testing (g-FOBT) have not been assessed.Population and methodsWe aimed to determine the reasons for current compliance with FIT among non-responders to g-FOBT, termed “converts‿, in a French district. A questionnaire was returned by 170 converts aged from 55 to 75 years (response rate 75.2% after exclusions).ResultsThe major barriers to participation in screening with g-FOBT were test-related: the test was perceived as complicated (24%) and it required three consecutive stools (28%). Among the test-related major determinants of FIT compliance was the perception that the test was less complicated than previous test (30%) and that a unique stool sample was required (29%). Among the non-test related major determinants of FIT compliance were the perception that the general practitioner was more convincing (31%) and the feeling to be more concerned because of age (21%). The reasons for compliance among converts did not differ according to age, sex, and rural or urban residence.ConclusionsOur study demonstrated that the simplicity of FIT and the endorsement of practitioners were both major motivations for FIT compliance among non-respondents in at least two previous consecutive campaigns.     

Proportional incidence of interval colorectal cancer in a large population-based faecal immunochemical test screening programme

BackgroundThe European guidelines for quality assurance in colorectal cancer (CRC) screening recommend that interval cancer rate be expressed as a proportion of background incidence rate.AimTo determine the crude and adjusted proportional incidence of interval CRC in an Italian regional two-yearly faecal immunochemical test (FIT) screening programme.MethodsThe programme (year of implementation, 2005) is targeted at over 1,000,000 people aged 50–69 years. The test is a one-sample OC-Sensor (Eiken Chemical Co., Tokyo, Japan). The study covered one-third of the regional area. Excerpts of 434,295 eligible negative FIT records dated 2005–2012 from 193,193 subjects were retrieved from the regional CRC screening data warehouse. By 31 December 2013, the cohort accumulated 198,302 man-years and 235,370 woman-years. Interval CRCs were identified by record-linkage with the local population-based cancer registry. Their number was divided by the expected number, estimated with age-period-cohort models, to obtain the proportional incidence.ResultsThe proportional incidence of interval CRC for men and women was, respectively, 0.06 (95% confidence interval (CI), 0.04–0.09) and 0.17 (95% CI, 0.13–0.23) in the first interval year, and 0.21 (95% CI, 0.16–0.26) and 0.28 (95% CI, 0.22–0.36) in the second year.ConclusionsThe results were acceptable and in line with previous studies.     

Randomized study of biennial screening with a faecal occult blood test: results after nine screening rounds

Background: Two large true population studies in Europe have shown a significant reduction in mortality from colorectal cancer (CRC) by screening with a faecal occult blood test. In one trial conducted in Funen County, 61,933 individuals (aged 45–75 years) were randomly allocated either to a control group or to receive a biennial Hemoccult‐II test. Methods: These individuals were followed from 1985 to 2002 and 9 screening rounds were performed. Results: First screening was accepted by 67% (20,672). Positivity rates varied between 0.8% and 3.8%, and the cumulative proportion of the test group having colonoscopy was 5.3%. Screen‐detected CRC was early (Dukes' A) in 36% compared to 11% among controls. Incidence of CRC was unchanged, but mortality was reduced by 11%. This figure increased to 43% in persons participating in all 9 rounds. No more than 8,558 were screened at the 9th round. Patients with CRC detected between screenings had better survival than controls. Death rates from causes other than CRC among participants never became higher than among controls. Conclusion: The lesser reduction in mortality from CRC of 11% compared to 18% after 5 screening rounds may be explained by the decrease in the number screened. Efficacy in those screened supports the introduction of countrywide screening in Denmark, but it must be ascertained that acceptability, proportion of early CRC and logistics all reach the same standard as in the randomized trial.     

Fecal immunochemical test in cancer screening – colonoscopy outcome in FIT positives and negatives

Objectives: Fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, but evaluations of multiple sample strategies in colonoscopy screening cohorts are rare. The aim of this study was to assess accuracy of FIT for advanced neoplasia (AN) with two fecal samples in a colonoscopy screening cohort.

Materials and methods: The study comprised 1155 participants of the colonoscopy arm in SCREESCO (Screening of Swedish Colons, NCT02078804), a randomized controlled study on CRC screening of 60-year-olds from the Swedish average-risk population. Participants provided two FIT samples prior to colonoscopy. First sample, mean of two, and any of the two samples above cut off level were assessed. Colonoscopy findings (CRC, advanced adenoma (AA), AN (CRC?+?AA) and adenoma characteristics) were evaluated in uni- and multivariable analysis in relation to FIT positivity (at ≥10?µg hemoglobin (Hb)/g).

Results: Of 1155 invited, 806 (416 women, 390 men) participated. CRC, AA and non-AA were found in one (0.1%), 80 (9.9%) and 145 (18%), respectively. Sensitivity and specificity for AN were 20%/93%, 25%/92% and 26%/89% for first, mean of two and any of the two samples respectively at cut off level 10?µg/g, corresponding to 60 (74%)–65 (80%) participants with missed AN. The difference in sensitivity between screening strategies was non-significant. The specificity for first sample was significantly higher than for any of the two samples at cut off 10?µg/g (p?=?.02) and 20?µg/g (p?=?.04). FIT positivity in participants with adenoma was associated with pedunculated shape (p?=?.007) and high-risk dysplasia (p?=?.009).

Conclusions: In an average-risk colonoscopy screening cohort of 60-year-olds, sensitivity for AN was modest and did not increase when using two samples instead of one. FIT predominantly detected adenomas with pedunculated shape and high-risk dysplasia, and participants with flat or broad based adenomas may thus be missed in screening.     

Fecal immunochemical test accuracy in average-risk colorectal cancer screening

AIM:To assess the fecal immunochemical test(FIT)accuracy for colorectal cancer(CRC)and advanced neoplasia(AN)detection in CRC screening.METHODS:We performed a multicentric,prospective,double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy.Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample(FIT1)and the highest level of both samples(FITmax)using the OC-sensor.Areas under the curve(AUC)for CRC and AN were calculated.The best FIT1and FITmax cut-off values for CRC were determined.At this threshold,number needed to scope(NNS)to detect a CRC and an AN and the cost per lesion detected were calculated.RESULTS:About 779 individuals were included.An AN was found in 97(12.5%)individuals:a CRC in 5(0.6%)and an advanced adenoma(≥10 mm,villous histology or high grade dysplasia)in 92(11.9%)subjects.For CRC diagnosis,FIT1 AUC was 0.96(95%CI:0.95-0.98)and FITmax AUC was 0.95(95%CI:0.93-0.97).For AN,FIT1 and FITmax AUC were similar(0.72,95%CI:0.66-0.78 vs 0.73,95%CI:0.68-0.79,respectively,P=0.34).Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28%and 42%and specificity between 91%and 97%.At the best cut-off point for CRC detection(115 ng/mL),the NNS to detect a CRC were 10.2 and 15.8;and the cost per CRC was 1814€and 2985€on FIT1 and FITmax strategies respectively.At this threshold the sensitivity,NNS and cost per AN detected were 30%,1.76,and 306€,in FIT1 strategy,and 36%,2.26€and 426€,in FITmax strategy,respectively.CONCLUSION:Performing two tests does not improve diagnostic accuracy,but increases cost and NNS to detect a lesion.     

Potential for prevention: a cohort study of colonoscopies and removal of adenomas in a FIT-based colorectal cancer screening programme

Introduction: Evidence suggests that colorectal cancer (CRC) screening using guaiac faecal occult blood tests (gFOBT) reduces the CRC burden by facilitating timely removal of adenomas. Yet, the faecal immunochemical test (FIT) is being implemented in many countries. The aim of this study was to analyse the risk of having adenomas detected when invited for FIT-based screening as compared to those not yet invited.

Material and Methods: The study was designed as a register-based retrospective cohort study. The potential for prevention was estimated as number of individuals who had no adenomas, non-advanced adenomas, and advanced adenomas detected per 1000 invited/not yet invited individuals and the relative risk (RR) of each of the three outcomes.

Results: A total of 1,359,340 individuals were included, 29.6% of whom had been invited and 70.4% had not yet been invited to participate in CRC screening. Compared with the not yet invited population, the invited group had a RR of no adenomas of 2.28 (2.22–2.34) and a RR of advanced adenomas of 7.41 (6.93–7.91). The RR of colonoscopy was 2.93 (2.87–2.99) for the invited population compared with the not yet invited population.

Conclusion: The RR of having a colonoscopy was three times higher among those invited compared to those not yet invited for CRC screening and twice as often those who had been invited compared to those not yet invited had no adenomas detected. Still, the risk of advanced adenomas was more than seven times higher among the invited population, indicating that the screening programme holds great potential for reducing the CRC burden.

Abbreviations: CI: Confidence interval; CRC: Colorectal cancer; FIT: Faecal immunochemical test; ICD: International Classification of Disease; RR: Relative risk     

The Usefulness of a Novel Screening Kit for Colorectal Cancer Using the Immunochromatographic Fecal Tumor M2 Pyruvate Kinase Test

Background/AimsM2 pyruvate kinase (M2-PK) is an enzyme that is produced in undifferentiated and proliferating tissues. This study aims to evaluate the usefulness of the immunochromatographic M2 pyruvate kinase (iM2-PK) for the screening of colorectal cancer (CRC) and premalignant lesions.MethodsHealthy volunteers and patients with colorectal neoplasia were enrolled in six academic hospitals in the capital province of Korea. The iM2-PK value was compared with the immunochromatographic fecal occult blood test (iFOBT) and fecal tumor M2-PK enzyme-linked immunosorbent assay (ELISA).ResultsA total of 323 subjects were enrolled. The sensitivity of iM2-PK for CRC was 92.8%, which was superior to iFOBT (47.5%, p<0.0001). For adenomatous lesions, the sensitivity of iM2-PK was 69.4%, which was also superior to iFOBT (12.1%, p<0.001). Compared with M2-PK ELISA, iM2-PK exhibited significantly enhanced sensitivity for CRC (97.5% vs 80.0%, p=0.0289). The sensitivity of iM2-PK was higher in advanced stages of CRC compared with cancers confined to the mucosa and submucosa (p<0.05). However, lymph node metastasis had no influence on the sensitivity of iM2-PK.ConclusionsThe iM2-PK exhibited increased sensitivity for identifying CRC and adenomatous lesions compared with iFOBT. Given its rapid results and convenience, CRC screening using iM2-PK is promising.     

Performance of the Fecal Immunochemical Test for Colorectal Cancer Screening Using Different Stool-Collection Devices: Preliminary Results from a Randomized Controlled Trial

Background/AimsWe are in the process of conducting a randomized trial to determine whether compliance with the fecal immunochemical test (FIT) for colorectal cancer screening differs according to the stool-collection method. This study was an interim analysis of the performance of two stool-collection devices (sampling bottle vs conventional container).MethodsIn total, 1,701 individuals (age range, 50 to 74 years) were randomized into the sampling bottle group (intervention arm) or the conventional container group (control arm). In both groups, we evaluated the FIT positivity rate, the positive predictive value for advanced neoplasia, and the detection rate for advanced neoplasia.ResultsThe FIT positivity rates were 4.1% for the sampling bottles and 2.0% for the conventional containers; these values were significantly different. The positive predictive values for advanced neoplasia in the sampling bottles and conventional containers were 11.1% (95% confidence interval [CI], −3.4 to 25.6) and 12.0% (95% CI, −0.7 to 24.7), respectively. The detection rates for advanced neoplasia in the sampling bottles and conventional containers were 4.5 per 1,000 persons (95% CI, 2.0 to 11.0) and 2.4 per 1,000 persons (95% CI, 0.0 to 5.0), respectively.ConclusionsThe impact of these findings on FIT screening performance was unclear in this interim analysis. This impact should therefore be evaluated in the final analysis following the final enrollment period.