Zohar Levi

Use of Enalapril To Attenuate Decline in Renal Function in Normotensive, Normoalbuminuric Patients with Type 2 Diabetes Mellitus: A Randomized, Controlled Trial

The concept of microalbuminuria has had a major impact on diabetes research and clinical care of patients with diabetes [1-5]. Initial albuminuria is regarded by most researchers as an independent predictor of subsequent progression of nephropathy and risk for cardiovascular morbidity and mortality [6-8]. Angiotensin-converting enzyme (ACE) inhibitors have been found to attenuate progression of nephropathy in both types of diabetes in hypertensive [9-12] and normotensive patients [13-15] with microalbuminuria. They were also found to lower urinary albumin excretion in normotensive and normoalbuminuric patients with type 1 diabetes [16]. The relation between albuminuria and later progression of nephropathy in these patients has not been established, possibly because of short follow-up periods. No data are available on the effect of early introduction of ACE inhibitors in normotensive and normoalbuminuric patients with type 2 diabetes mellitus. We designed a randomized, double-blind, placebo-controlled trial of the effect of ACE inhibition on the course of nephropathy in 156 patients with type 2 diabetes. These patients had normal blood pressure and normal urinary albumin excretion at baseline. Methods Patients Potential candidates were identified through the computerized records of the central regional laboratory for the northern part of the greater Tel-Aviv area. Persons with hyperglycemia and normal urinalysis results were located through their family physicians. Consent was sought once eligibility was established. Inclusion criteria were age younger than 60 years; age 40 years or older at diagnosis; duration of diabetes mellitus less than 10 years with no clinical evidence of malignant, autoimmune, hepatic, cardiovascular, or renal disease; body mass index less than 30 kg/m2; normal blood pressure on at least two consecutive visits (systolic pressure 140 mm Hg and diastolic pressure 90 mm Hg; mean pressure 107 mm Hg); serum creatinine concentration of 123 mol/L or less; and urinary albumin excretion of 30 mg/24 h or less. All baseline data were obtained twice during the run-in prerandomization period. Patients were eligible only if values within the predetermined range were found on both examinations. The average of the values was used as the baseline value. A total of 255 patients who had type 2 diabetes according to World Health Organization criteria [17] and attended one of eight clinics in the greater Tel-Aviv area were found to be eligible and were contacted during 1990 and 1991. Of these patients, 214 gave informed consent to participate. Twenty patients were excluded during the observation period: Six had blood pressure values above normal, 5 had microalbuminuria, 3 had serum creatinine concentrations above the trial criterion, 1 patient developed unstable angina pectoris, and 5 withdrew consent. Of the 194 patients included in the study, 102 were women and 92 were men (mean age SD, 54.9 3.2 years [range, 37 to 59 years]). The known duration of diabetes was 0 to 9 years (mean duration, 5.75 2.8 years). Patients were instructed to use the standard isocaloric diet recommended by the Israeli Diabetic Association, and 69 study patients used diet alone to control their hyperglycemia. Pharmacologic therapy for diabetes was insulin in 34 patients and oral hypoglycemic agents in 91 patients. Protocol The protocol was approved by the hospital review board. After a 2-month observation period, patients were randomly assigned in a double-blind manner to receive enalapril (Assia-Riezel Ltd., Ramat-Gan, Israel), 10 mg/d, or placebo. Ninety-seven patients were assigned to receive enalapril, and 97 were assigned to receive placebo. Randomization was done centrally by telephone with a random number table [18]. Patient allocation to placebo or enalapril was recorded and kept by one of the authors. The placebo tablets were similar in appearance to the enalapril tablets. The medications, which came in sealed, numbered packages, were centrally prepared and were given to the patients at each visit by one nurse who was otherwise not involved in the study. Patients were followed by their family physicians, who were unaware of allocation. Two semiannual prescheduled visits took place each year, and interim visits were scheduled as clinically indicated. At the semiannual visits, hemoglobin A1c values, serum creatinine concentrations, serum electrolyte levels, and 24-hour albumin excretion and urinary creatinine concentrations were measured. Blood pressure was measured by the physicians twice at each visit by using mercury sphygmomanometers with the patients seated after a 5-minute rest; physicians recorded the average of the two values. The diastolic pressure was determined at Korotkoff phase V. If a systolic blood pressure of 145 mm Hg or more or a diastolic blood pressure of 95 mm Hg or more was found, measurements were repeated weekly. If elevated values persisted on two consecutive visits, a long-acting calcium-channel blocker (diltiazem or verapamil), hydrochlorothiazide, or both were administered. If systolic blood pressure values of 100 mm Hg or less were repeatedly found, the enalapril dosage was reduced to 5 mg/d (half of a 10-mg enalapril tablet or half of a placebo tablet). Fundoscopy was done yearly by an ophthalmologist, and the presence of retinopathy was recorded. For each patient, follow-up was terminated 6 years after randomization. Measurements All blood and urine samples were examined by a central laboratory. Assays were not changed during the study period. Glycosylated hemoglobin values were measured by affinity chromatography with a commercial kit (Isolab, Biochemical Methodology, Akron, Ohio). The normal range of this assay is a hemoglobin A1c value of 3.5% to 5.6% and an intra-assay and interassay coefficient of variability of less than 3%. Urinary albumin concentration was measured twice in 24-hour urine samples by an automated immunoturbidimetric method [19]. This procedure has intra-assay and interassay coefficients of variability of 5.9% and 7.6%, respectively. Creatinine concentrations were determined by using the automated method of Bartels and colleagues [20]. Creatinine clearance, normalized for 1.73 m2 of body surface area, was calculated for each visit by using the standard formula (urine creatinine x urine volume/plasma creatinine). The mean blood pressure (defined as the diastolic pressure plus one third of the pulse pressure) was calculated at each visit. Statistical Analysis Data are expressed as the mean (SD) with ranges. A P value less than 0.05 was considered significant. On the basis of the assumptions that 15% of normotensive, normoalbuminuric patients with type 2 diabetes will develop microalbuminuria during 6 years and that treatment with enalapril will reduce the risk for microalbuminuria by 12%, we calculated that 69 patients were required in each group for a type 1 error of 0.05 and a power of 0.80 [21]. To test for adequate randomization and to compare the patients who completed the trial with those who did not complete the trial, the enalapril and placebo groups and the 38 patients who dropped out were compared for mean age; mean duration of diabetes; and mean baseline albumin excretion, creatinine clearance, glycosylated hemoglobin value, and blood pressure by using pooled-variance Student t-tests for independent groups and one-way analysis of variance. To compare the annual means of the various measurements between the two groups and within each group, one between-group factor and one repeated-measures factor were used in analysis of variance. For variables shown to be different by analysis of variance, unpaired t-tests were used for between-group parallel annual means and paired t-tests were used for comparison of intragroup sequential annual means. The rate of decrease of creatinine clearance and the rate of increase of albumin excretion were computed by doing linear regression analysis with all of the semiannual values included in the equation. Urinary albumin values were logarithmically transformed before analysis. The degree of albuminuria at baseline was used as a covariate. The funding source had no involvement in the design, conduct, or reporting of the trial. Results Figure 1 shows the flow of participants during the trial. Thirty-eight patients did not complete the trial. Five patients died (3 in the enalapril group and 2 in the placebo group); death was related to coronary heart disease in 3 patients, stroke in 1 patient, and ovarian carcinoma in 1 patient. Six patients violated the protocol (2 patients in the enalapril group stopped taking their medication for more than 6 months, and 4 patients in the placebo group took an ACE inhibitor prescribed by consultant physicians for more than 6 months). Ten patients were lost to follow-up (6 in the enalapril group and 4 in the placebo group). The trial medication was discontinued in 12 patients: Six developed a disturbing cough (4 in the enalapril group and 2 in the placebo group), 4 had an allergic skin reaction (2 in the enalapril group and 2 in the placebo group), 1 patient in the enalapril group developed leukopenia, and 1 patient in the placebo group developed hyperkalemia. Finally, 5 patients developed severe urinary tract infections that had a detectable influence on renal function (2 in the enalapril group and 3 in the placebo group). A total of 156 patients completed the trial, of whom 77 received enalapril and 79 received placebo. Figure 1. Flow of participants through the trial. Baseline data for the two groups and for patients who did not complete the trial are shown in Table 1. The baseline characteristics of patients in the study groups and those who dropped out did not differ significantly. A modest but steady decrease in hemoglobin A1c values was seen in the enalapril and the placebo groups and may reflect the change in attitude toward glucose control among family physicians in the early 1990s. However, t

A Quantitative Immunochemical Fecal Occult Blood Test for Colorectal Neoplasia

Context Although screening with a guaiac-based fecal occult blood test (FOBT) reduces colorectal cancer mortality, better tests are needed. Contribution In the study, 1000 patients undergoing diagnostic colonoscopy provided fecal samples that a clinical laboratory tested with a quantitative immunochemical test for hemoglobin. Hemoglobin content was highest in samples from people with significant neoplasia, for which sensitivity and specificity were 67% and 91%, respectively. Positive and negative likelihood ratios were 7.8 and 0.36, respectively. Cautions The authors did not compare the immunochemical FOBT with guaiac-based FOBT. The study included people with symptoms. Implications The quantitative immunochemical test for fecal hemoglobin is a promising test that needs evaluation in a screening population. The Editors A colorectal cancer screening test should identify persons with early-stage cancer that is an immediate medical threat and persons with advanced adenomas that could be a future threat. As well as having high sensitivity, the screening test should have high specificity for detecting clinically significant neoplasia, cancer, and advanced adenomas to minimize follow-up colonoscopy examinations (1). The commonly used guaiac-based fecal occult blood tests (FOBTs) have low specificity for detecting human hemoglobin and relatively low sensitivity for identifying clinically significant colorectal neoplasia (18). Office-developed qualitative immunochemical FOBTs are specific for detection of human hemoglobin and have improved test specificity (1, 46, 913). However, the manufacturers designed the test to have sensitivity for measuring hemoglobin similar to that of a sensitive guaiac-based FOBT, which is a limitation. Moreover, we found that doing the actual measuring in the office was not conducive to large-scale screening while maintaining quality control (1, 2, 6). We investigated a clinical laboratorybased immunochemical test that measures the hemoglobin content of a stool sample. Laboratory-based, automated, immunochemical measurement of fecal human hemoglobin eliminates the need for diet restrictions, is specific for human hemoglobin, and allows for quality control. In addition, clinicians can choose a fecal hemoglobin threshold level to perform colonoscopy and can adjust this threshold to take account of the patients risk for advanced neoplasia and the availability of quality colonoscopy (1, 1420). The quantitative immunochemical FOBT has been evaluated in Japan and elsewhere (1422). However, to our knowledge, no English-language publication systematically compares fecal immunochemical hemoglobin content with total colonoscopy findings. We aimed to measure the sensitivity and specificity of different levels of fecal hemoglobin for detecting clinically significant colorectal neoplasia versus colonoscopy, to determine the posttest probability of advanced neoplasia at different fecal hemoglobin threshold values, and to determine the optimal number of fecal samples. Methods Patients We asked consecutive ambulatory persons who were referred for colonoscopy to volunteer to prepare immunochemical FOBTs for research purposes. Some patients were asymptomatic and were invited for elective colonoscopy, some patients were at high risk for colorectal cancer (these patients were from our clinic), and some patients were symptomatic and were referred by their treating physician (Table 1 and Figure 1). We have reported partial findings on the initial 500 patients (20). Table 1. Baseline Characteristics* Figure 1. Study flow diagram. I-FOBT = immunochemical fecal occult blood test; IBD = inflammatory bowel disease. Exclusions were concurrent hospitalization, visible rectal bleeding, known diagnosis of inflammatory bowel disease, hematuria, menstruation at the time of obtaining a stool specimen, and inability to prepare the immunochemical FOBT (Figure 1). We did not exclude patients with long-term use of nonsteroidal anti-inflammatory drugs or anticoagulant therapy that was stopped for colonoscopy. Endoscopy and Lesions We inserted the colonoscope to the cecum or an obstructing carcinoma. We excluded 49 patients with an incomplete colonoscopy. Biopsy was done on lesions or they were removed, and their sites were noted. We classified abnormal findings by number of polyps, polyp sizes, and sites grouped by location (proximal [colon cecum to and including splenic flexure] or distal colon) and by histologic characteristics. The endoscopist estimated polyp size with a calibrated open biopsy forceps. We grouped adenomas and mass lesions by diameter or size (5 mm, 6 to 9 mm, or 10 mm) and by histologic characteristics (tubular, serrated, tubulovillous, or villous). We classified dysplasia as low grade or high grade. Pathologists were blinded to the immunochemical FOBT results. Clinically significant neoplasia includes colorectal cancer or advanced polyps (adenomas 10 mm in diameter, adenomas with 20% villous histologic characteristics, or any high-grade dysplasia regardless of size) (23). We classified patients with more than 1 lesion according to the most advanced lesion. We reexamined all advanced adenomas smaller than 10 mm to confirm their histologic diagnosis (24). Fecal Sampling Participants received an explanation of the test and written instructions on how to prepare the fecal samples. After voiding urine and flushing the toilet before having a bowel movement, participants placed a disposable paper float in the toilet bowl to immobilize the stool for easy sampling (Appendix Figure 1). Each fecal sample tube has a unique bar code. Before preparing the sample, the patient wrote his or her name and the date on the tube. The immunochemical FOBT sampling probe is inserted into an 8-cm2-cm test tubeshaped container. The patient inserts the probe into several different areas of the stool and then reinserts it firmly into the tube to seal it (Appendix Figure 2). The probe tip with the fecal sample is suspended in a standard volume of hemoglobin-stabilizing buffer. According to the manufacturers manual, the amount of stool obtained by this process is semistandardized (but does depend on fecal consistency) at 10 mg (SD, 0.5). According to the manufacturers data, the mean specimen size ranges from 9.03 mg (SD, 0.29) for diarrhea to 11.89 mg (SD, 0.76) for hard stools. Examinees prepared 3 daily or consecutive samples during the week before colonoscopy examination. They observed no dietary or medication restrictions other than stopping aspirin and anticoagulant therapy before endoscopy. Samples were stored in double ziplock bags at 4C until development within 2 weeks (20, 25). We processed the samples by using the OC-MICRO instrument (Eiken Chemical Co., Tokyo, Japan) as described in the Appendix. Appendix Figure 1. Folded paper float opened ( left ) and placed in toilet bowl ( right ). After defecation and fecal sampling, the participant flushes the float into the toilet. Appendix Figure 2. Stool probe and fecal sample storage tube. The patient removes the fecal probe that has a serrated tip that accumulates the fecal sample. The probe is then reinserted deeper into the tube past a scraper and through a membrane that removes excess feces. The bottom compartment of the tube contains a 2-mL buffer solution for stabilizing the fecal specimen in the tip serrations. For pricing the immunochemical FOBT at

Performance Characteristics and Evaluation of an Automated-Developed and Quantitative, Immunochemical, Fecal Occult Blood Screening Test

20, we used the local agents price for 3 tests and added administrative costs. In comparison, the authorized pricing (from Israels Ministry of Health) is

Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

13 for screening with 3 guaiac-based FOBTs. The ethics committee of the Rabin Medical Center, Tel Aviv, Israel, approved the study in 2004. All participants gave written informed consent for the immunochemical FOBT and colonoscopy examination. Statistical Analysis We recorded each patients most severe pathologic finding (histologic characteristics, polyp size, and number of polyps) and the highest amount of fecal hemoglobin measured in that patients 3 immunochemical FOBT samples. We classified persons with only small rectal hyperplastic polyps as not having neoplasia. We analyzed fecal hemoglobin measurements according to the number of adenomas (<3 adenomas or 3 adenomas), lesion size, site in the colon (proximal or distal), and histology. We analyzed colorectal cancer and advanced adenoma separately and together as clinically significant colorectal neoplasia. Since the study sample was heterogeneous, we compared the sensitivity and specificity of the immunochemical FOBT in the 3 main categories of reason for referral (Appendix Table 1) by using the chi-square test and Fisher exact test. Appendix Table 1. Immunochemical Fecal Occult Blood Test and Endoscopy Results for Cancer or Clinically Significant Neoplasia, by Reasons for Colonoscopy* To classify a patients fecal hemoglobin level as normal or abnormal, we used 2 thresholds: the published and manufacturer-suggested threshold of 100 ng/mL of buffer and a threshold of 75 ng/mL, which we thought would give a higher sensitivity for detecting clinically significant neoplasia (14, 15, 20). We also repeated these analyses at different thresholds in increments of 25 ng/mL, ranging from 50 ng/mL to 200 ng/mL. We measured the diagnostic value of the immunochemical FOBT for detecting clinically significant neoplasia by using 5 criteria: sensitivity, specificity, likelihood ratios, and posttest probability after a negative and positive result. We compared sensitivity and specificity by using threshold values of 75 ng/mL or greater and 100 ng/mL or greater for abnormal findings and the McNemar test for symmetry. We reported polyp sizes and fecal hemoglobin measurements as means (SDs) and by quartiles. We also reported 95% CIs for means and likelihood ratios (26). Since the distribution of fecal hemoglobin measurements was not normally distributed, we used 1) a parametric test for log2-transformed data (since log of 0 is not defin

A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test, despite lower compliance rate. A prospective, controlled, feasibility study

OBJECTIVES:Guaiac fecal occult blood colorectal cancer (CRC) screening tests (FOBT) are faulted for low sensitivity and nonspecificity for human hemoglobin (Hb). Automated-developed, immunochemical, human Hb FOBT (I-FOBT) is specific, eliminates diet restrictions, and Hb quantification allows selection of a threshold for colonoscopy. Aims were to determine 1) test reproducibility; 2) test stability; 3) intrapatient daily I-FOBT variation; 4) test sensitivity and specificity for neoplasia in 500 symptomatic/high-risk patients undergoing colonoscopy; and 5) to correlate fecal Hb measurements with findings.METHODS:The desktop instrument OC-Sensor (Eiken, Japan) automatically develops and quantitates 50 tests/h for Hb. Patients prepared three tests, which were quantified and then 1) repeatedly re-examined; 2) stored at 4°C or 20°C or 28°C and repeatedly examined; and 3) fecal Hb levels were correlated with colonoscopic findings.RESULTS:Five I-FOBTs re-examined five times in 1 day had no significant measurement changes. Thirty tests stored for 21 or more days had a decay/day of 0.3%± 0.4 at 4°C (NS), 2.2%± 1.7 at 20°C (NS), and 3.7%± 1.8 at 28°C (p < 0.05). There were intrapatient variations between the three daily I-FOBTs (NS). At the recommended 100 ng Hb/mL threshold, all six cases of CRCs and 20 out of 28 cases of advanced adenomas were detected; evaluated together their sensitivity and specificity were 76.5% and 95.3%.CONCLUSIONS:Desktop, automated-developed, quantitative I-FOBT is now available. Refrigerated OC-Sensor samples are stable for 21 days, easy to prepare and develop and, at the 100 ng Hb/mL threshold, have high sensitivity, specificity, and negative predictive values for significant neoplasia. Suitability for population CRC screening awaits further evaluation.

Sensitivity, but Not Specificity, of a Quantitative Immunochemical Fecal Occult Blood Test for Neoplasia Is Slightly Increased by the Use of Low-Dose Aspirin, NSAIDS, and Anticoagulants

BACKGROUND AND STUDY AIMS The Capsule Endoscopy Crohns Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. METHODS This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohns disease. The CECDAI was designed to evaluate three main parameters of Crohns disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. RESULTS The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohns Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. CONCLUSION A new scoring system of mucosal injury in Crohns disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated.

A quantitative immunochemical faecal occult blood test is more efficient for detecting significant colorectal neoplasia than a sensitive guaiac test

Immunochemical fecal occult blood test (FIT) is a new colorectal cancer (CRC) screening method already recommended by the American screening guidelines. We aimed to test the feasibility of FIT as compared to guaiac fecal occult blood test (G‐FOBT) in a large urban population of Tel Aviv. Average‐risk persons, aged 50–75 years, were offered FIT or G‐FOBT after randomization according to the socioeconomic status of their clinics. Participants with positive tests underwent colonoscopy. Participants were followed through the Cancer Registry 2 years after the study. Hemoccult SENSA™ and OC‐MICRO™ (three samples, 70 ng/ml threshold) were used. FIT was offered to 4,657 persons (Group A) and G‐FOBT to 7,880 persons (Group B). Participation rate was 25.9% and 28.8% in Group A and B, respectively (p < 0.001). Positivity rate in Group A and B was 12.7% and 3.9%, respectively (p < 0.001). Cancer found in six (0.49%) and eight (0.35%) patients of Group A and B, respectively (NS). Cancer registry follow‐up found missed cancer in five (0.22%) cases of Group B and none in Group A (NS). The sensitivity, specificity, negative and positive predictive value for cancer in Group A and B were 100%, 85.9%, 100%, 3.9% and 61.5%, 96.4%, 99.8%, 9.1%, respectively. There was increased detection of advanced adenomatous polyp (AAP) by FIT, irrespective of age, gender, and socioeconomic status (Per Protocol: odds ratio 2.69, 95% confidence interval 1.6–4.5; Intention to Screen: odds ratio 3.16, 95% confidence interval 1.8–5.4). FIT is feasible in urban, average‐risk population, which significantly improved performance for detection of AAP and CRC, despite reduced participation.

Measured Body Mass Index in Adolescence and the Incidence of Colorectal Cancer in a Cohort of 1.1 Million Males

OBJECTIVES:We evaluated the effect of the use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), and anticoagulants on the performance of immunochemical fecal occult blood test (I-FOBT).METHODS:A prospective, cross-sectional study of 1,221 ambulatory patients having total colonoscopy after preparing three I-FOBTs. Information regarding the use of medications was collected from the health medical organization (HMO) database. I-FOBT was analyzed with the OC-MICRO instrument using both ≥75 and 100 ngHb/ml of buffer thresholds to determine positivity.RESULTS:Colorectal cancer (CRC) was found in 17 and advanced adenomatous polyp (AAP) in 97 patients. A total of 212 patients were using aspirin/NSAIDS at the time of I-FOBT testing. Qualitative analysis for the detection of AAP/CRC reveals a trend for an increased sensitivity with aspirin/NSAIDS use. At the threshold 75 ng/ml for positivity, the sensitivity for the detection of AAP/CRC was 66.7% for aspirin/NSAIDS use vs. 51.2% for nondrug takers (P=0.20), and at the threshold of 100 ng/ml, the sensitivity was 66.7 vs. 46.5% (P=0.09). The specificity, however, was not affected by the use of aspirin/NSAIDS. At the threshold of 75 ng/ml for positivity, the specificity for the detection of AAP/CRC was 89.5% for aspirin/NSAIDS use vs. 91.2% for nondrug takers (P=0.47), and at the threshold of 100 ng/ml, the specificity was 92.17 vs. 93.0% (P=0.69). A total of 33 patients were using antithrombotics/coagulants at the time of I-FOBT testing. This group was small; however, it appears that their use was also associated with a trend for increased sensitivity and no change in specificity.CONCLUSIONS:The use of aspirin/NSAIDS and anticoagulants was associated with a trend for increased sensitivity with no change in specificity for the detection of AAP/CRC. This study suggests that there is no need to stop these agents before I-FOBT testing.

Quantitative colonoscopic evaluation of relative efficiencies of an immunochemical faecal occult blood test and a sensitive guaiac test for detecting significant colorectal neoplasms

The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS; Beckman Coulter, Fullerton, CA, USA), is our standard screening test for significant colorectal neoplasia. We evaluated an automatically‐developed, quantified human haemoglobin immunochemical faecal test, OC‐MICRO (Eiken Chemical Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy burden.

Cumulative Evaluation of a Quantitative Immunochemical Fecal Occult Blood Test to Determine Its Optimal Clinical Use

Background and Aims: The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with colorectal cancer incidence in a large cohort of males. Methods: Body mass index (BMI) was measured in 1.1 million Jewish Israeli males who underwent a general health examination at ages 16 to 19 between 1967 and 2005. Overweight was defined as BMI ≥ 85th percentile of the standard U.S. distribution in adolescence. Colorectal cancer was identified by linkage with the Israel National Cancer Registry up to 2006. The mean follow-up period was 17.6 ± 10.9 years, reflecting 19.5 million person-years. Cox proportional hazards modeling was used. Results: The prevalence of adolescent overweight increased from 9.9% to 16.8% in the first 10 and last 10 annual examination cohorts. Colon (n = 445) and rectal cancer (n = 193) cases were detected. Overweight predicted an increased risk of colon cancer [HR = 1.53; 95% confidence interval (CI), 1.17–2.02, P = 0.002] but not of rectal cancer (HR = 1.09; 95% CI, 0.38–1.73, P = 0.72). The risk was greatest for nonmucinous adenocarcinoma of the colon (HR = 1.68, 95% CI, 1.26–2.23, P = 0.001). The association of BMI ≥ 85th percentile with colon cancer was even more pronounced in analyses that were restricted to men followed until at least 40 years of age [N = 367,478; HR = 1.75 (95% CI, 1.33–2.3, P < 0.001)]. Conclusions: Adolescent overweight is substantially associated with colon cancer incidence in young to middle-aged adults. Impact: These long-term sequelae add to the urgency to seriously address increasing childhood and adolescent obesity with its attendant increasing population impact. Cancer Epidemiol Biomarkers Prev; 20(12); 2524–31. ©2011 AACR.