Occult blood screening for colorectal carcinoma: A critical review

Objectives. —To define the validity of fecal blood as a marker for colorectal neoplasia in the screening setting and to compare yields by Hemoccult and HemoQuant fecal occult blood screening tests. Design. —A multicenter masked comparison of fecal blood test results against structural colorectal evaluations and longitudinal follow-up, serving as criterion standards, in nonreferred subjects at risk for colorectal neoplasia. Setting. —Communities, primary care centers, referral centers. Participants. —Two groups: (1) 1217 patients aged at least 18 years undergoing routine structural surveillance evaluations following curative resection of a colorectal tumor and (2) 12312 relatives of colorectal cancer patients aged at least 50 years. Interventions. —Blinded Hemoccult II and HemoQuant testing on three mailedin stool samples per subject. Main Outcome Measure. —Sensitivity of fecal blood tests for colorectal neoplasia. Results. —In the postresection group, surveillance evaluations revealed 46 malignant colorectal neoplasms and 402 polyps. At matched specificity, sensitivity of either test for cancer was 26% (95% confidence interval, 13% to 39%). Hemoccult was positive in 21% of intraluminal recurrences, 33% of all new primary tumors, and 29% of Dukes A or B cancers; HemoQuant was elevated in 24%, 28%, and 29%, respectively. Sensitivity for polyps 1.0 cm or larger was 13% by Hemoccult and 11% by HemoQuant. In the group of relatives, estimated sensitivity for cancer at 1 to 3 years of follow-up was 25% to 33% by Hemoccult, not significantly different from the 29% to 43% by HemoQuant. Conclusions. —Based on our observations in the screening setting, fecal blood appears to be a poor marker for colorectal neoplasia. Most cancers and the vast majority of polyps will be missed. Hemoccult and HemoQuant are similarly insensitive. ( JAMA . 1993;269:1262-1267)

Accuracy of fecal occult blood screening for colorectal neoplasia : a prospective study using Hemoccult and HemoQuant tests

The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin.

The hookworms Necator americanus and Ancylostoma duodenale infect approximately 1 billion people worldwide. The prevalence of hookworm infection increases with age in children, typically reaching a plateau in late adolescence, whereas the intensity of infection may continue to increase throughout adulthood. Hookworms cause intestinal blood loss in amounts proportional to the number of adult worms in the gut. The relationship between hookworm infection intensity and hemoglobin concentration is evident in epidemiologic studies, but may be apparent only above a threshold worm burden that is related to the iron stores of the population. Current hookworm control efforts are focused on reducing infection load and transmission potential through periodic anthelmintic chemotherapy. Several controlled trials have demonstrated a positive impact of anthelmintic treatment on hemoglobin levels, with best results obtained in settings where iron intakes were also increased. Evidence suggests that anthelmintic programs will have modest impacts on iron deficiency anemia in the short term, with greater impacts on more severe anemia. Hookworms are an important cause of anemia in women, who are often overlooked by current helminth control programs. Current WHO recommendations for use of anthelminthics in schoolchildren and women are reviewed. There is a need to clarify whether hookworms are an important etiology of iron deficiency anemia in preschool children.

Hookworm Control as a Strategy to Prevent Iron Deficiency

Aim
Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous thromboembolism. This study examined the safety, pharmacokinetics and pharmacodynamics of multiple dose apixaban.

Method
This double-blind, randomized, placebo-controlled, parallel group, multiple dose escalation study was conducted in six sequential dose panels – apixaban 2.5, 5, 10 and 25 mg twice daily and 10 and 25 mg once daily– with eight healthy subjects per panel. Within each panel, subjects were randomized (3:1) to oral apixaban or placebo for 7 days. Subjects underwent safety assessments and were monitored for adverse events (AEs). Blood samples were taken to measure apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and modified prothrombin time (mPT).

Results
Forty-eight subjects were randomized and treated (apixaban, n = 36; placebo, n = 12); one subject receiving 2.5 mg twice daily discontinued due to AEs (headache and nausea). No dose limiting AEs were observed. Apixaban maximum plasma concentration was achieved ∼3 h post-dose. Exposure increased approximately in proportion to dose. Apixaban steady-state concentrations were reached by day 3, with an accumulation index of 1.3–1.9. Peak : trough ratios were lower for twice daily vs. once daily regimens. Clotting times showed dose-related increases tracking the plasma concentration–time profile.

Conclusion
Multiple oral doses of apixaban were safe and well tolerated over a 10-fold dose range, with pharmacokinetics with low variability and concentration-related increases in clotting time measures.

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Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects

We describe a new, specific, quantitative method for fecal blood, based on conversion of nonfluorescing heme to fluorescing porphyrins, that obviates serious deficiencies inherent in currently used tests. A two-reagent system is used to determine the two hemoglobin-related fractions that are found in feces. The hot citric acid extract includes only the variable fraction of porphyrins that have been preformed from heme in the intestinal tract; this often is the major fraction. Total hemoglobin is indirectly determined by reaction with heated oxalic acid:FeSO4 reagent, which converts the remaining heme to porphyrin without loss of the preformed porphyrins. A three-step purification procedure eliminates interfering materials. Analytical recovery of added hemoglobin is linearly related to concentration over a several-thousand-fold range. The assay is equally applicable to whole blood or to sub-microgram amounts of hemoglobin in the 8-mg (wet weight) fecal sample tested. Quality control by liquid chromatographic and fluorometric analysis documents fluorescence specificity of the heme-derived porphyrins.

M Ellefson

Papers

The "HemoQuant" test: a specific and quantitative determination of heme (hemoglobin) in feces and other materials.