Int J Colorectal Dis (1999) 14:267–271
© Springer-Verlag 1999
O R I G I N A L A RT I C L E
Andreas Sieg · Christine Thoms · Kai Lüthgens Markus R. John · Heinrich Schmidt-Gayk
Detection of colorectal neoplasms by the highly sensitive hemoglobin-haptoglobin complex in feces
Accepted: 25 October 1999
Abstract Screening for fecal occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. The immunological determination of human hemoglobin in feces has a higher sensitivity and specificity, but hemoglobin is degraded during its transport through the gastrointestinal tract. We compared the hemoglobin test to a newly developed immuno-chemiluminometric (ILMA) assay for quantifying the hemoglobin-haptoglobin complex in feces which shows high stability against degradation. From each of 621 patients with gastrointestinal complaints before scheduled colonoscopy we collected two 1-ml samples from a single stool; there were no dietary restrictions. The sensitivity for detecting colorectal carcinomas proved 87% with hemoglobin. With the hemoglobinhaptoglobin complex it was 87% at a cutoff level of 1.5 µg/g feces, 83% at 2.0 µg/g feces, and 78% at 2.5 and 3.0 µg/g feces. The sensitivity for detecting large adenomatous polyps was 54% with hemoglobin, 76% with the hemoglobin-haptoglobin complex at a cutoff point of 1.5 µg/g feces, 73% with the hemoglobin-haptoglobin complex at 2.0 and 2.5 µg/g feces, and 65% with the hemoglobin-haptoglobin complex at 3.0 µg/g feces. The optimal cutoff point for the hemoglobin-haptoglobin complex was estimated to be 2.0 µg/g stool. The specificity for hemoglobin (99%) was significantly higher than that for the hemoglobin-haptoglobin complex at 2.0 µg/g feces (96%). Immunological determination of the hemoglobin-haptoglobin complex in feces has a comparable sensitivity as the fecal hemoglobin assay for A. Sieg (✉) Practice of Gastroenterology, Hauptstrasse 45, D-76684 Östringen, Germany e-mail:
[email protected], Tel.: +49-6221-21806, Fax: +49-6221-27454 K. Lüthgens · M.R. John · H. Schmidt-Gayk Laboratory Group, University of Heidelberg, Heidelberg, Germany A. Sieg · C. Thoms · M.R. John · H. Schmidt-Gayk Department of Medicine, University of Heidelberg, Heidelberg, Germany
colorectal carcinomas and a significantly higher sensitivity for adenomatous polyps but a significantly lower specificity. Its use for colorectal cancer prevention is currently being evaluated in a screening study. Key words Colorectal cancer · Colonic polyps · Hemoglobin-haptoglobin complex · Occult blood · Hemoglobin
Introduction Guaiac tests are widely used in colorectal cancer screening to detect fecal occult blood (FOB), although they have an unsatisfactory sensitivity for detecting colorectal neoplasms in asymptomatic patients [1–4]. In a group of 248 patients with positive fecal guaiac tests who underwent colonoscopy followed by esophago-gastro-duodenoscopy upper gastrointestinal lesions were identified more frequently than colonic lesions [5]. FOB screening with guaiac tests reveal significantly fewer colorectal neoplasms than sigmoidoscopy [6]. A major disadvantage of guaiac tests is the fact that they are not specific for human blood and can produce positive results when meat, fruit, or vegetables containing peroxidase have been ingested [7]. The rate of false-negative results is increased by large amounts of vitamin C [8]. Nevertheless, the mortality rate from colorectal cancer could reportedly be reduced by 15–18% with biennial screening using nonrehydrated guaiac tests [9, 10] and by 33% with annual screening using rehydrated guaiac tests [11]. A meta-analysis with four randomized and two nonrandomized trials of Hemoccult screening showed a 16% reduction in mortality from colorectal cancer [12]. When adjusted for attendance at screening, this reduction was 23% for persons actually screened [12]. Given the more sophisticated immunological screening techniques to detect constituents of human blood in feces, it should be possible to reduce mortality from colorectal cancer even further. A higher sensitivity and specificity of immunological tests for hemoglobin (Hb) in the detection of co-
268 um azide, and 0.4 g EDTA per liter. The diluted samples were mixed thoroughly and centrifuged for 15 min at 3000 g, and the supernatants were measured in luminescence immunoassays specific for human Hb or the HbHp complex. The luminescence immunoassay for Hb was set up according to Gao et al. [21] and that for the HbHp complex according to Lüthgens et al. [20]. The upper limit of normal for human hemoglobin was set at 10 µg/g feces, according to our earlier findings [16]. For the HbHp complex the optimal threshold value was to be found. The detection limit was about 1 µg/g feces for human Hb and 0.03 µg/g feces for the HbHp complex. Diagnosis was based on the endoscopic and histopathological findings. Carcinomas were classified according to the UICC stages I–IV of the TNM system, and location. Adenomatous polyps were classified as to histopathological characteristics, size (large polyps: >1 cm; small polyps
