Immunological Fecal Occult Blood Test Research Articles

Screening for Colorectal Cancer by Immunological Fecal Occult Blood Test: Number Needed to Screen and to Scope to Find One Advanced Neoplasm

REDUCED RENAL FUNCTION IS ASSOCIATEDWITH ANEMIA DURING TREATMENT WITH PEGINTERFERON/RIBAVIRIN IN ELDERLY CHRONIC HEPATITIS C PATIENTS R. Ceriani∗ ,1, M. Andreoletti 2 , G. Borroni 3, A. Bortoli 4 , M. Casiraghi 5, M. Cazzaniga6 , P. Guerzoni7 , G. Mandelli 8 , B. Omazzi 4, M.G. Pich1, A. Prada4, N. Terreni 8, G. Spinzi 8 1Irccs Istituto Clinico Humanitas, Rozzano (MI), Italy; 2Ospedale A Manzoni, Lecco, Italy; 3Asl Milano 1, Milano, Italy; 4Ospedale G Salvini, Rho (MI), Italy; 5Ospedale Civile, Legnano, Italy; 6Irccs Policlinico S. Donato, S Donato Milanese (MI), Italy; 7Ospedale Varese, Varese, Italy; 8Ospedale Valduce, Como, Italy

Anticoagulant or aspirin treatment does not affect the positive predictive value of an immunological fecal occult blood test in patients undergoing colorectal cancer screening

The immunochemical fecal occult blood test (i-FOBT) is widely used as a recommended screening strategy for colorectal cancer (CRC). A growing number of patients potentially targeted by CRC screening programs are on oral anticoagulant or chronic low-dose aspirin therapy, mainly for primary or secondary cardiovascular prophylaxis. This study aims at evaluating whether the use of these medications may impact on the diagnostic performances of i-FOBT for CRC screening. All i-FOBT-positive patients on anticoagulant or chronic low-dose aspirin therapy recorded in a regional mass screening program database were enrolled as cases. Control groups were derived from the same database and included drug-naive i-FOBT-positive patients, matched in a ratio of 1 : 2 for age (± 3 years of age), sex, date of colonoscopy, and practice site. Information about the use of medications was collected by cross-checking patients' interview before colonoscopy and data recorded in the provincial electronic registry of medical prescriptions. The positive predictive value of i-FOBT for significant neoplasia (high-risk adenoma and CRC) was calculated in the case and control groups. In a 2-year study period, 2376 patients were recorded in the regional database. Of these patients, 53 (2%) were on anticoagulation (control group of 106 patients) and 172 (6.6%) were on chronic low-dose aspirin treatment (control group of 344 patients). Significant neoplasia was detected in 15 (28.3%) patients on anticoagulants and in 37 (34.9%) corresponding controls (P=0.45). Significant neoplasia was detected in 50 (29.1%) patients on chronic low-dose aspirin and in 107 (31.1%) corresponding controls (P=0.64). The positive predictive value of i-FOBT for significant neoplasia is not affected by ongoing anticoagulant or chronic low-dose aspirin therapy. This finding suggests that there is no need to interrupt these treatments before i-FOBT for CRC screening.

Incremental net benefit and acceptability of alternative health policies: a case study of mass screening for colorectal cancer

The incremental net benefit (INB) and the related acceptability curves for public health programs provide valuable tools for decision making. We proposed to apply them to the assessment of mass screening of colorectal cancer. The now standard guaiac fecal occult blood test (FOBT) is already implemented in several countries. We considered the innovative immunological FOBT and computed tomography colonography (CTC) as competing screening technologies. Using biennial guaiac FOBT as the reference strategy, we estimated the cost-effectiveness of the following alternatives: biennial immunological FOBT, CTC every 5 years (strategy CTC5), and CTC every 10 years (strategy CTC10). Over a 30-year horizon and from the perspective of a third-party payer, we developed a Markov model on a hypothetical cohort of 100,000 subjects at average risk of colorectal cancer. Close expected net benefits between immunological FOBT and CTC5 induced uncertainty in the choice of the optimal strategy. Probabilistic sensibility analysis then suggested that below a willingness to pay (WTP) per life-years gained (LYG) of 8,587 €/LYG, CTC10 was optimal, while CTC5 would be preferred beyond a WTP of 8,587 €/LYG.

A simplified, non-invasive fecal-based DNA integrity assay and iFOBT for colorectal cancer detection

Neoplasia cells exfoliated from colorectal epithelium have dysfunctional apoptotic mechanisms, thus it is possible to identify high-molecular weight DNA fragments in feces. This prospective single-center study was performed to evaluate the sensitivity and specificity of fecal-based DNA integrity versus immunological fecal occult blood test (iFOBT) and calprotectin for colorectal cancer (CRC) and adenoma detection. Feces were collected from 204 subjects and DNA integrity was quantified by quantitative-denaturing high performance liquid chromatography (QdHPLC). Calprotectin and iFOBT were assessed using commercial kits. The diagnostic performance was calculated by receiver operating characteristic (ROC) curves analysis. A total of 192 fecal specimens were analyzed and 12 samples were excluded due to DNA degradation. We found long DNA (L-DNA) occurrence in feces with a sensitivity of 86% (n = 24/28) and a specificity of 81% for CRC detection. To minimize false-positive cases of the developed test, area under the curve of ROC was evaluated such that the specificity was increased to 92% with decreased sensitivity to 79%, p = 0.0001 for CRC detection. iFOBT was positive in 51% (n = 14/27) while calprotectin was positive in 75% (n = 18/27). The combination of iFOBT and L-DNA identified a greater number of CRC cases with a sensitivity of 89% and a specificity of 95%, p < 0.001. The combination also improved the sensitivity of polyps, particularly high-grade dysplasia and advanced adenoma (33%, p = 0.0015) as opposed to a single evaluation assay (17-21%). This study illustrates the usefulness of fecal DNA integrity assay by QdHPLC as a non-invasive, easy-to-perform, and reproducible method with a high level of sensitivity in detecting individuals with colorectal neoplasia. Combination of iFOBT and L-DNA improves the sensitivity for CRC and adenoma detection.

Cost-effectiveness of colorectal cancer screening with computed tomography colonography or fecal blood tests

To assess the cost-effectiveness of colorectal cancer screening using computed tomography colonography (CTC) and immunological fecal occult blood test (iFOBT). CTC and iFOBT strategies were compared with Nn screening or guaiac FOBT (gFOBT) using Markov modeling. CTC was proposed at 50, 60, and 70 years, whereas gFOBT and iFOBT were performed every 2 years beginning at 50 years until 74 years of age with a 30-year time horizon. We calculated incremental cost-effectiveness ratios and efficiency ratios (ERs). Then, we performed univariate and probabilistic sensitivity analyses. With gFOBT as reference, colorectal cancer prevention rate was 18% for CTC and 11% for iFOBT. The incremental cost-effectiveness ratio of CTC and iFOBT were respectively 3204 and 5458 euro per life years gained (LYG), the ER for CTC was 0.22 and the ER for iFOBT was 2.08 colonoscopies per LYG. Cost-effectiveness results were sensitive to CTC cost. In the probabilistic sensitivity analysis, compared with CTC, iFOBT strategy was cost-effective for 84.6% of simulations when we assumed a willingness to pay (WTP) of 20,000 euro/LYG. CTC requires substantially less colonoscopies than iFOBT and is cost-effective for low values of WTP. However, iFOBT is the preferred screening strategy for a WTP greater than 6207 euro/LYG.

Comparison of guaiac and immunological fecal occult blood tests in colorectal cancer screening: The patient perspective

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.

From Research to Clinical Application Multi-Parameter Testing: Marker Panels for the Early Detection of Complex Diseases

From Research to Clinical Application Multi-Parameter Testing: Marker Panels for the Early Detection of Complex DiseasesMulti Parameter Analysis can open novel diagnostic opportunities for the early diagnosis and screening of multimodal diseases like cancer. Single proteins have so far failed to describe such complex diseases. Being able to screen with a set of analytes is one promising way to overcome the present limitations. Various marker identification tools including proteomics approaches have been successfully applied to identify new screening markers for early detection of colorectal cancer (CRC). CRC is one of the most incident cancers worldwide and early detection is clearly a key factor in reducing mortality from CRC. Several screening methods are recommended, including colonoscopy, fecal occult blood testing (FOBT) and fecal DNA analysis. Of these annual stool testing with the guaiac based FOBT is most often applied, in spite of limitations such as low sensitivity and dietary influences. Though proce dures with improved performance eg. immunolo gical FOBT are available, a screening assay for CRC in serum that could easily be integrated in any health check-up would be highly welcome. A positive result of such a test would trigger a follow-up colonoscopy for an exact diagnosis. In this review we will cover aspects of marker identification strategies and describe a well structured marker validation process that is based on clinically characterized sample materials. Finally the value of analytical multi-parameter platforms enabling the combination of multi markers in routine diagnostics settings is outlined. An appropriate multi-parameter immunochemistry platform concept, currently developed under the working name »IMPACT« will be introduced.

T2032 Screening for Colorectal Cancer By Immunological Fecal Occult Blood Test: Results of Four Rounds in Two Municipalities of Aosta Valley (Italy)

T2032 Screening for Colorectal Cancer By Immunological Fecal Occult Blood Test: Results of Four Rounds in Two Municipalities of Aosta Valley (Italy)

Colorectal Advanced Adenomas: Frequency in Population At Risk and Correlation with the Quantitative Immunological Occult Blood Test

Introduction: Colorectal cancer (CCR) is the most frequent digestive neoplasia; typically, more than 90% arise from an adenoma. Advanced Adenomas (AA) are lesions ≥10 mm, villous component ≥25% or high degree dysplasia with major risk of malignization. The Program of Prevention and Early Detection of CCR uses Immunological Faecal Occult Blood Test (IFOBT) as a screening to quantify haemoglobin of the faecal matter; those patients with levels ≥100 ng hb/ml were sent to colonoscopy. Our aims were to compare the frequency of AA in two groups: asymptomatic with IFOBT ≥100 ng hb/ml versus symptomatic. They were referred for colonoscopy. A second aim was to correlate of the size of the adenoma with the IFOBT. Methodology: We designed an observational study from of 2829 consecutive patient's sent to colonoscopy between April, 2000 and December, 2007 at the Digestive Cancer Center of the National Cancer Institute of Montevideo, Uruguay. Previous informed assent, we collected clinical, demographic information, presence of adenoma (size, topography and histology) and IFOBT quantification (ng hb/ml). Groups: 1) asymptomatic, >50 years old with IFOBT ≥100 ng hb/ml (n=1927), and 2) symptomatic (n=902). Statistical analysis was performed chi square, Student t-test, and multiple lineal correlations with SPSS 17.0 for Windows and Epi Info ver. 3.3.2.0. Results: The asymptomatic group (n=1927) were 81 (Females 31) AA from 902 (8.9%) IFOBT positive patients. Sixty five patients had only one AA (80.2%) and 16 two or more (19.8%). Size: ≤ 9 mm (n=22, 27,2%), 10-15 mm (n=51, 62.9%) and ≥16 mm (n=8, 9.9%). The quantification with IFOBT showed a positive correlation with the size of the adenoma. Interestingly, there was a point of inflexion at 15 mm size, where the IFOBT values stop increasing (flat curve) at the interval between 1100 and 1900 ng Hb. For every mm that increases the size, the IFOBT increased 35 ± 9 ng Hb. The symptomatic group had 105 AA out of 1927 (5.1%) symptomatic patients. No differences were observed by age, sex or place of the lesions. Conclusions: The comparison between those two different groups at risk allows detecting incipient lesions asymptomatic patients. The use of the IFOBT as a screening tool for colonoscopy detected a major frequency of advanced adenomas in asymptomatic patients that in symptomatic. In patients with average risk for colorectal cancer the IFOBT is a useful tool for screening; colonoscopy in patients with positive test showed that the size of the adenoma is in directly relation with the level of the microhemorrhage.

Negative Predictive Value of Immunological Fecal Occult Blood Test in Patients with Adenocarcinoma of Unknown Origin with a Suspicion of Primary Colorectal Cancer

Negative Predictive Value of Immunological Fecal Occult Blood Test in Patients with Adenocarcinoma of Unknown Origin with a Suspicion of Primary Colorectal Cancer

Improved Diagnosis of Colorectal Cancer Using a Combination of Fecal Occult Blood and Novel Fecal Protein Markers

Annual testing for fecal occult blood is recommended as first-line screening for the detection of colorectal cancer (CRC), but is affected by limited sensitivity. We initiated a proteomics-based search for novel biomarkers to improve the sensitivity of detection of CRC in stool samples. Six markers, including immunologic fecal occult blood test (iFOBT), were evaluated in a collective of 551 samples (186 CRC, 113 advanced adenoma, and 252 control patients) to establish the diagnostic performance of each marker and marker combinations. We tested the known stool markers hemoglobin (iFOBT), hemoglobin-haptoglobin, calprotectin, carcinoembryogenic antigen, and the novel fecal markers tissue inhibitor of metalloproteinase-1 (TIMP-1) and S100A12. The best diagnostic performance was found for S100A12 with an area under the curve of 0.95, followed by TIMP-1 (0.92), hemoglobin-haptoglobin (0.92), hemoglobin (0.91), calprotectin (0.90), and carcinoembryogenic antigen (0.66). By using Bayes logistic regression as a mathematic model, the highest sensitivity (88%) for the detection of CRC at 95% specificity was obtained with the marker pair S100A12 and hemoglobin-haptoglobin. Increasing the specificity to 98%, the combination of S100A12, hemoglobin-haptoglobin, and TIMP-1 resulted in a sensitivity of 82%, with the highest increase of sensitivity found in early tumor stages (international union against cancer stage I: 74% sensitivity vs 57% of the best single marker). Depending on the specificity selected, a marker pair, S100A12 and hemoglobin-haptoglobin, or a triple combination including TIMP-1, allowed the detection of CRC at significantly higher rates than can be obtained with iFOBT alone.

Evaluation of Calgranulin B in Stools from the Patients with Colorectal Cancer

Calprotectin (heterodimer of calgranulin A and B) has been previously studied as a candidate stool marker for detecting colorectal cancer. We assessed the clinical usefulness of calgranulin B as a stool marker for colorectal cancer in a pilot study of patients with colorectal cancer. We performed 2-DE-based proteomics to screen stool markers for colorectal cancer. We checked the calgranulin B in stools from 77 colorectal cancer patients and from 75 controls by western blot and enzyme-linked immunosorbent assay. We measured calgranulin A using the same methods, and stool hemoglobin by immunologic fecal occult blood test. Fecal calgranulin A did not show any difference, but stool calgranulin B of colorectal cancer patients was significantly higher than controls [50.6 ng/mg stool protein (SD, 34.8) vs. 20.2 ng/mg stool protein (SD,24.0), respectively, P < 0.001). At the cut off level 24.4 ng/mg stool protein, the sensitivity was somewhat higher than fecal occult blood test (72.0 percent vs. 62.3 percent) but the specificity was much lower than fecal occult blood test (77.1 percent vs. 98.7 percent). Calgranulin B was increased in stools of colorectal cancer patients but our results suggest that colorectal cancer screening by determination of stool calgranulin B would not be better than conventional fecal occult blood test.

Comparison of an Established Simple Office-Based Immunological FOBT With Fecal Tumor Pyruvate Kinase Type M2 (M2-PK) for Colorectal Cancer Screening: Prospective Multicenter Study

The immunological fecal occult blood test (IFOBT) has established itself as a more precise marker for colorectal cancer (CRC) screening than traditional guaiac-based FOBT. The simpler, cheaper, and more convenient newer office-based IFOBTs have been validated for diagnosing CRC. Dimeric isoenzyme of pyruvate kinase, M2-PK, expressed by tumor cells, has as well been proposed as a screening tool for CRC. This is the first study comparing fecal M2-PK as a screening biomarker for CRC against previously evaluated office-based IFOBT and colonoscopy. Six hundred forty consecutive subjects (symptomatic, as well as for CRC screening) referred for colonoscopy for various indications across five centers in Germany provided the stool samples for performing M2-PK and an immunochemical FOB strip test. The IFOBT used was a rapid immunochromatographic assay for detection of fecal hemoglobin. For M2-PK, a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) was used. The M2-PK test needs 6 h, while the office-based test can be read in just 10 min and is five times cheaper. Office-based IFOBT had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LR) of 64.5, 96.3, 72.0, 94.9, 17.5, and 0.4 for diagnosing colorectal neoplasia (CRN), while the above performance characteristics for M2-PK at a cutoff value of 4 U/mL were 72.4, 73.8, 29.0, 94.8, 2.8, and 0.8 respectively. This office-based IFOBT was found to have significantly higher specificity, PPV, and positive LR as compared with M2-PK. IFOBT proved to be a convenient, noncumbersome, quick, and cheap tool in patients with above-average risk for detection of CRN.

Immunological Fecal Occult Blood Test Versus Serum Ferritin for the Detection of Colorectal Neoplasia in An Asymptomatic Population At High Risk for Cancer

Immunological Fecal Occult Blood Test Versus Serum Ferritin for the Detection of Colorectal Neoplasia in An Asymptomatic Population At High Risk for Cancer

What percent should be a reasonable positivity rate of immunological fecal occult blood testing?

What percent should be a reasonable positivity rate of immunological fecal occult blood testing?

Comparing Attendance and Detection Rate of Colonoscopy With Sigmoidoscopy and FIT for Colorectal Cancer Screening

We conducted a study to estimate population coverage and detection rate (DR) achievable through different strategies of colorectal cancer (CRC) screening. A population-based multicenter randomized trial comparing 3 strategies was used: (1) biennial immunologic fecal occult blood test (FIT), (2) "once only" sigmoidoscopy (FS), and (3) "once only" colonoscopy (TC). A random sample of men and women, aged 55 to 64 years, was drawn from general practitioners' (GP) rosters. Eligible subjects, randomized within GP, were mailed a personal invitation. Nonresponders in groups 2 and 3 were invited again at 12 and 24 months. Screenees with "high-risk" distal polyps (villous component >20%, high-grade dysplasia, CRC, size >or=10 mm, >2 adenomas) at FS, or with positive FIT, were referred for TC. The attendance rate was 32.3% (1965/6075) for FIT, 32.3% (1944/6018) for FS, 26.5% (1597/6021) for TC. FIT detected 2 patients with CRC (0.1%) and 21 with an advanced adenoma (1.1%). The corresponding figures were as follows: 12 (0.6%) and 86 (4.5%) patients, respectively, for FS; 13 (0.8%) and 100 (6.3%) patients, respectively, for TC. To detect 1 advanced neoplasm, it would be necessary to invite 264 people with FIT, 60 with FS, 53 with TC. FS would have detected 27.3% of the proximal advanced neoplasms detected at TC. Assuming the same participation rate at TC as at FS, 48 TCs would be necessary to detect 1 additional advanced neoplasm missed by FS. When participants are offered 1 screening test, participation is lower in a TC than in an FS program. However, DR of advanced neoplasia is higher with TC.

The detection rates and tumor clinical/pathological stages of whole-body FDG-PET cancer screening

FDG-PET has been used for cancer screening, mainly in East-Asia, and cancers are found not infrequently. However, their stages have not been clarified. We examined the detection rates of various cancers using whole-body PET for the screening of cancers in asymptomatic individuals, focusing on their clinical and pathological stages. Whole-body PET was obtained as a part of our cancer screening program among 3,426 healthy subjects. All subjects participated in a course of PET examination in conjunction with conventional examinations including a medical questionnaire, tumor markers, immunological fecal occult blood test, neck and abdominal ultrasonography and whole body computed tomography. A diagnosis and staging was obtained by an analysis of the pathological findings or by an analysis of the clinical follow-up data. Malignant tumors were discovered in 65 lesions found in 3,426 participants (1.90%). The PET findings were true-positive in 46 of the 65 cancer cases. The cancers were found in the following organs: the colon 14; thyroid gland 10; stomach 7; lung 5; liver 3; breast 2; and one each in the kidney, gallbladder, esophagus, pancreas and retroperitoneum. The stages were as follows: stage 0 5, stage I 17, stage II 10, stage III 7, and stage IV 6. One was an unknown primary. There were 19 false-negative findings (0.6%) on PET. Six cancers (0.18%) were missed in our screening program. PET imaging has the potential to detect a wide variety of cancers at potentially curative stages. Most PET-negative cancers are early stage cancers, and thus can be detected using other conventional examinations such as endoscopy.

A Review of False Negative Findings in Immunological Fecal Occult Blood Testing.

A Review of False Negative Findings in Immunological Fecal Occult Blood Testing.

Association of FOBT-assessed faecal Hb content with colonic lesions detected in the Florence screening programme

We assessed the correlation between quantitative results of immunological faecal occult blood testing (I-FOBT) and colonic lesions (191 colorectal cancers, 890 adenomas) detected at colonoscopy in 2597 FOBT+ (cutoff 100 ng ml−1 Hb) subjects. At univariate analysis, a higher average faecal Hb content was significantly associated with male gender (P=0.003), age (P=0.02), and colonoscopy findings (P=0.000). Among adenomas, higher faecal Hb content was significantly associated with size (P=0.0000), presence of severe dysplasia (P=0.0001), presence of villous component (P=0.0002), and location in the left colon (P=0.003). At multivariate analysis adjusting for potential confounders, age (P=0.03), size (P=0.0000), and location in the left colon (P=0.0005) were confirmed as having an independent association with higher faecal Hb content. Immunological FOBT is confirmed to be a specific screening test to detect cancer and adenoma, with a low positivity rate (3.7%) and a high positive predictive value (41.5%). Faecal Hb content is significantly higher for those lesions (cancer and high-risk adenomas) screening is aimed at detecting.

COMMUNITY‐BASED MASS SCREENING FOR COLORECTAL CANCER BY A COMBINATION OF FECAL OCCULT BLOOD TESTING AND FLEXIBLE SIGMOIDOSCOPY

Background: There have only been a few large‐scale community‐based reports on the combination of immunological fecal occult blood testing (IFOBT) and flexible sigmoidoscopy (FS). Based on the results of mass screening at our hospital, we investigated the utility of combining IFOBT with FS to detect colorectal cancer (CRC) and analyzed the detection rates of CRC.Subjects and methods: The subjects comprised examinees during mass screening for CRC from 1992 to 2002. Only examinees that underwent the 2‐day IFOBT method were enrolled. During the 11 years, 117 644 subjects had negative 2‐day IFOBT and underwent FS. Cancers that were directly found by FS or by work‐up examinations with negative 2‐day IFOBT were designated as IFOBT‐FS‐detected cancers.Results: The detection rate of CRC was 0.16% (mucosal cancer, 0.13%; invasive cancer, 0.03%) by negative 2‐day IFOBT and FS. It was 0.27% (mucosal cancer, 0.22%; invasive cancer, 0.05%) in first‐time examinees. The detection rate was significantly higher in males than in females, and rates increased with age in both genders. Adverse events included eight cases of ischemic colitis that occurred after FS (incidence rate, 0.0068%). There were no cases of perforation, hemorrhage or infection after endoscopy.Conclusion: Although there are problems in introducing FS into mass screening for CRC, such as cost‐effectiveness, speed of examinations and lack of manpower, FS is expected to prevail because preparation is easier, and it is a shorter and safer procedure than colonoscopy. In particular, a combination of IFOBT with FS is effective and recommended in first‐time examinees and for individuals 50 years and older. Mass screening using the combination of IFOBT and FS provides limited benefit in those who are below 50 years of age.