Interval fecal immunochemical testing in a colonoscopic surveillance program speeds detection of colorectal neoplasia.

BACKGROUND & AIMS: Rapidly progressing or missed lesions can reduce the effectiveness of colonoscopy-based colorectal cancer surveillance programs. We investigated whether giving fecal immunochemical tests (FITs) for hemoglobin between surveillance colonoscopies resulted in earlier detection of neoplasia. METHODS: The study included 1736 patients with a family history or past neoplasia; they received at least 2 colonoscopy examinations and were followed for a total of 8863 years. Patients were excluded from the study if they had genetic syndromes, colorectal surgery, or inflammatory bowel disease. An FIT was offered yearly, in the interval between colonoscopies; if results were positive, the colonoscopy was performed earlier than scheduled. RESULTS: Among the 1071 asymptomatic subjects (61%) who received at least 1 FIT, the test detected 12 of 14 cancers (86% sensitivity) and 60 of 96 (63%) advanced adenomas. In patients with positive results from the FIT, the diagnosis of cancer was made 25 months (median) earlier and diagnosis of advanced adenoma 24 months earlier. Patients who had repeated negative results from FIT had an almost 2-fold decrease in risk for cancer and advanced adenoma compared with patients who were not tested (5.5% vs 10.1%, respectively, P = .0004). The most advanced stages of neoplasia, observed across the continuum from nonadvanced adenoma to late-stage cancer, were associated with age (increased with age), sex (increased in males), and FIT result. The probability of most advanced neoplastic stage was lowest among those with a negative result from the FIT (odds ratio, 0.68; P < .001). CONCLUSIONS: Interval examinations using the FIT detected neoplasias sooner than scheduled surveillances. Subjects with negative results from the FIT had the lowest risk for the most advanced stage of neoplasia. Interval FIT analyses can be used to detect missed or rapidly developing lesions in surveillance programs.

In vivo mutagenic effect of very low dose radiation.

Almost all of our knowledge about the mutational effect of radiation has come from high dose studies which are generally not relevant to public exposure. The pKZ1 mouse recombination mutagenesis assay enables study of the mutational effect of very low doses of low LET radiation (microGy to cGy range) in a whole animal model. The mutational end-point studied is chromosomal inversion which is a common mutation in cancer. We have observed 1) a non-linear dose response of induced inversions in pKZ1 mice exposed to a wide dose range of low LET radiation, 2) the ability of low priming doses to cause an adaptive response to subsequent higher test doses and 3) the effect of genetic susceptibility where animals that are heterozygous for the Ataxia Telangiectasia gene (Atm) exhibit different responses to low dose radiation compared to their normal litter-mates.

The linear no-threshold model does not hold for low-dose ionizing radiation.

Almost all of the data on the biological effects of ionizing radiation come from studies of high doses. However, the human population is unlikely to be exposed to such doses. Regulatory limits for radiation exposure are based on the linear no-threshold model, which predicts that the relationship between biological effects and radiation dose is linear, and that any dose has some effect. Chromosomal changes are an important effect of ionizing radiation because of their role in carcinogenesis. Here we exposed pKZ1 mice to single whole-body X-radiation doses as low as 1 microGy. We observed three different phases of response: (1) an induction of inversions at ultra-low doses, (2) a reduction below endogenous inversion frequency at low doses, and (3) an induction of inversions again at higher doses. These results do not fit a linear no-threshold model, and they may have implications for the way in which regulatory standards are presently set and for understanding radiation effects.