Pathophysiology of Bleeding from Large Bowel Neoplasms

抄録

The early detection of large bowel cancer in populations is usually based on screening for blood products in the feces using "occult blood tests" (OBTs). The success of this screening depends in part on an understanding of the nature of bleeding from large bowel neoplasms, the chemical fate of blood products released into the lumen and the nature of products excreted in the feces, and the performance characteristics of the OBT used.
Studies have revealed certain facts about the nature of bleeding from large bowel neoplasms. Asymptomatic neoplasms may bleed but the amount is variable. Cancers bleed more re unt is variable. Cancers bleed more amount is variable. Cancers bleed more y bleed but the amount is variable. Cancers bleed more than adenomas, an large lesions tend to bleed more than small ones, yet the amount is not dependent on the stage of the cancer. The quantity of bleeding varies from day to day and bleeding may be intermittent. Furthermore, there is normal physiological microbleeding and overlap exists between the ranges of bleeding seen in normal subjects and those with adenomas or cancers. All of these facts must be considered when planning strategies for screening programs based on OBTs. While OBTs can detect presymptomatic lesions, they will always be more effective at detecting larger lesions; furthermore, the more often the test is repeated, the more likely it is to detect an intermittently bleeding lesion.
When blood enters the proximal gastrointestinal (GI) tract, the globin moiety of hemoglobin (Hb) is rapidly digested and, while a small fraction of the heme is absorbed, most of it is passed unchanged to the colon. Hb entering the large bowel lumen suffers a different fate. Globin may be degraded by luminal proteases, but only slowly. Heme itself may be de-ironed by bacteria to produce heme-derived porphyrins (HDPS). Thus, depending on the site of blood loss and amount of bleeding, feces will contain a mixture of intact Hb, free heme and HDPS. HDPS predominate for proximal GI bleeding, while intact Hb and heme predominate for distal bleeding. This variable degradation of Hb has major implications for the choice of OBT.
There are three main types of OBT - each type differs in its ability to detect the various Hb-derivatives in feces. The hems-porphyrin assays (e.g. HemoQuant^TM) detect Hb, heme and HDPs; they do not discriminate between proximal (e.g. aspirin-induced) and distal bleeding, unless the assay is modified to measure HDPs separately from all the products. The guaiac tests (e.g. Hemoccult^R, Shionogi B) detect Hb and heme, but rot HDPS and are, therefore, more sensitive for distal than proximal bleeding. However, their chemical sensitivity is not as great as that of the heme-porphyrin assays. The immunochemical tests (e.g. HemSp) detect only human Hb, thus they are selective for large bowel bleeding. Heme-porphyrin assays and guaiac tests may be affected by drugs and/or diet (giving both false-positives and negatives for blood or neoplasia). Immunochemical tests are not affected in this way. One must, therefore, select the test carefully to suit the clinical situation; immunochemical tests are inefficient at detecting proximal lesions, but this is useful in screening for bowel cancer.
Given that there is a low but definite physiological microbleeding, a critical issue is the ability of an OBT to discriminate between normal blood loss and the increased quantities observed when a neoplasm is present. The ability to discriminate might depend on the analyle being tested. To test this we have quantitated daily fecal loss (by radiochromium), fecal Hb plus heme plus HDPS (by HemoOuant), fecal Hb and heme (by HemOccult) and fecal Hb (by ELISA) concentrations, in normal and neoplasm-bearing subjects. Hb proved to be the best anafyte for discriminating between the two, although intact hems also provided good discrimination.