In this study, rectal ACF were removed and the rectum was re-assessed one year later. Despite the fact that all observed ACFs were removed at the baseline exam, the prevalence and mean number of ACF observed at year 1, 61% and 1.93, respectively, was only slightly, albeit statistically significantly (p=0.02), lower than that observed at baseline, 69% and 2.25. There was also a strong, statistically significant correlation between the prevalence and number of ACF at baseline and what was found one year later (p < 0.0001).
A number of explanations may explain these observations. The correlation of baseline and year one counts could be explained by an underlying tendency in some subjects to develop ACF; this tendency would then manifest itself in elevated counts at both exams. Alternatively, or additionally, some ACF may have not been removed at baseline, and these may have persisted at year one, so missed ACF may help explain the similarity in ACF count one year apart. Evidence suggests that the endoscopic detection of ACF is flawed, with considerable inter-observer variability 10
The year 1 ACF count is similar to the baseline ACF count, whether the ACFs observed at baseline are removed, as in the current study, or just observed, as occurred in our pilot, natural history study, where ACF at baseline were observed but not removed 9
. The mean number of ACF observed at year 1 when baseline ACF were left in situ was only slightly higher, 2.3, than the year 1 mean number observed in the current study of 1.93 (average baseline counts were similar in the two studies). That baseline removal had only a small effect on the year 1 count can be explained, at least in part, by the phenomenon of ACF regression. In the natural history study, 57% of baseline ACF were estimated to have regressed and 43% persisted, one year later 9
. If many ACF regress within a year, then removing ACF at baseline will not have a great affect on the ACF count one year later.
Few studies have examined ACF over time to evaluate ACF recurrence after removal. In the Adenoma Prevention with Celecoxib Trial, 45 subjects were examined at baseline and re-evaluated one year later 6
. The mean number of ACF at baseline and year 1 were similar, 8.3 and 6.2, respectively. However, the numbers of ACF were substantially higher than that seen in the current study, an observation which points to variability in ACF reproducibility which hinders comparisons across studies 10
Parallels between ACF and adenomatous polyps are notable. In this study the number of ACF at baseline and year 1 were strongly correlated, with a correlation coefficient of 0.44. Studies of adenomas have repeatedly reported a similar finding; namely, that after polypectomy, the number of adenomas at baseline is predictive of the number seen at repeat colonoscopy at 1–4 years 11–13
. We also observed a correlation in the location of ACF at baseline and at year 1. A similar finding has also been observed with adenomas; adenoma location at baseline and first surveillance are significantly correlated 12
. Regression, which was observed with ACF in our natural history study, has also been hypothesized to occur with adenomas 14
In an analysis of the baseline ACF exam in this cohort, we reported that cigarette smoking was associated with higher ACF prevalence and increased BMI was associated with lower ACF prevalence 8
. In this study of recurrent ACF, we also found a significant association with cigarette smoking; however, somewhat curiously, a significant OR was only seen for former smoking (OR=1.8), and not current smoking (OR=1.2). At baseline, ACF prevalence was associated more strongly with current (OR=2.6) as opposed to former (OR=1.6) smoking. Other studies have shown smoking to be a risk factor for prevalent ACF. For example, Moxon et al. showed that smokers had a significantly greater number of ACF than non-smokers and also demonstrated a significant dose-response effect (on ACF count) with number of pack years 3
Our previous finding that increased BMI was inversely associated with ACF was unexpected, since elevated BMI has been considered to be a risk factor for adenomas and colorectal cancer. Additionally, Swede et al. showed increased BMI to be associated with increased number of prevalent ACF 4
. Our result here, of a modest, but not statistically significantly elevated risk for recurrent ACF in obese subjects (OR=1.4) seems more in line with the literature than our earlier finding from the baseline exam.
This study sheds additional light on the role for ACF in research and clinical practice. In our multi-center study, we found serious limitations in ACF reproducibility, and a considerable dynamic to ACF progression, with evidence for regression and initiation within a relatively short time frame of 1 year 9,10
. Because of problems in the reliability of detection, we are skeptical of the use of ACF to predict clinical outcomes, and don’t believe there is a role for ACF detection in clinical practice 2,15
. Additionally, in contrast to animal models, where dysplastic ACF are commonly produced, dysplastic ACF are rarely detected in humans 2
. Thus, the conclusion from animal studies, that there likely is a link between preventing ACF and preventing colorectal cancer, may not be applicable in humans.
In conclusion, removal of ACF at baseline did not result in a markedly reduced number of ACF observed one year later, and the number of ACF observed at year 1 was generally comparable to the baseline level. The locations of ACF removed at baseline and those observed at year one were significantly correlated. Parallels between ACF and adenomas are notable, including a tendency for some individuals to develop recurrent lesions in similar locations, as well as the possibility of spontaneous regression. At this time however, there is no defined role for ACF detection in clinical practice.