FLAT COLORECTAL NEOPLASMS & CANCER
is the second most common cause of cancer-related death in the
majority of colon and rectal cancers that develop spontaneously appear
from premalignant polyps, which resemble fleshy protrusions sprouting
lining of the large bowel, cancer has also been reported, much less
to arise from lesions that have a flat shape, or even a slightly
appearance, with respect to the surrounding layer of tissue that forms
inner lining of the colon and rectum (the mucosa).
These less common forms of premalignant
colorectal lesions, often referred to as nonpolypoid colorectal
(NP-CRNs), were first widely
the Japanese medical literature, but were thought to occur only very
western populations. A
paper in the Journal of the American
Medical Association, however, suggests that NP-CRNs may not
be all that
uncommon in the
This new study, which included more than 1,800 patients, assessed the results from elective colonoscopy performed at a large Veterans Administration medical center in 2003 and 2004. Far from being rare, NP-CRNs were found in nearly 10% of the colonoscopies performed. The patients were then broken down into three subgroups for further analysis. Among patients undergoing colonoscopy for routine screening purposes, NP-CRNs were observed 5.8% of patients. Patients undergoing colonoscopy because of concerning symptoms (such as rectal bleeding, a change in bowel habits, or other gastrointestinal symptoms) were noted to have NP-CRNs in 6% of case. Among those patients undergoing colonoscopy because of a prior history of colorectal cancer, NP-CRNs were observed in more than 15% of patients, or 1 in every 6 or 7 patients previously treated for colorectal cancer.
When the results of biopsies taken from these NP-CRNs were assessed, more bad news resulted. Although fewer than 1% of all patients (and only 0.3% of the screening colonoscopy group patients) were discovered to have early cancerous changes within a NP-CRN lesion, a comparison between NP-CRNs and the more common colorectal polyps revealed a disturbing finding. Among all 3 subgroups of patients, the presence of early cancers within flat or depressed NP-CRNs occurred nearly 10 times as frequently as was seen in colorectal polyps. When looking at specific subgroups of patients, once again, this study revealed that in patients undergoing colonoscopy for routine screening purposes, NP-CRNs were 2 times as likely to harbor small cancers when compared to colorectal polyps. In those patients undergoing colonoscopy for surveillance purposes, because they had previously been diagnosed with colorectal cancer, NP-CRNs, when identified, were almost 64 times more likely to harbor early cancers when compared to polypoid masses! When comparing the flat type of NP-CRNs with the depressed type, the depressed lesions were most likely to contain cancer (33% of the depressed lesions already had cancer cells present in them). These worrisome findings are all the more concerning given that, on average, the NP-CRNs containing cancer tended to be considerably smaller than the polyps also found to have cancer present in them (1.6 centimeters in diameter vs. 1.9 centimeters, respectively).
The findings of this study raise several important new considerations with respect to colorectal cancer screening strategies. First of all, despite the previous belief that NP-CRNs were rare lesions within western populations, this study suggests that, in fact, they are rather common, at least in a selected group of veterans (on average, veterans tend to have a greater incidence of risk factors associated with colorectal cancer than the general population).
The finding that, irrespective of the size of the lesions, that NP-CRNs are more likely to harbor small cancerous tumors suggests that the biology of these flat or depressed lesions may be different than that of the more typical, and more common, polypoid lesions. In this study, a special colored dye was used to stain the lining of the colon and rectum, which made it easier to detect NP-CRNs. However, this technique is not generally used in routine colonoscopy at most endoscopy centers, and the results of this study, therefore, raise the issue as to whether or not this technique should be routinely added to the current practice of colonoscopy. Also, even with special staining of the mucosa, NP-CRNs are still more difficult to identify than polypoid lesions, and the borders, or margins, of these flat or slightly depressed lesions are less distinct than is the case for polyps.
The current data in the medical literature suggests that approximately 10% of polyps may be missed, even by experienced examiners, during routine colonoscopy. Given the greater difficulty of identifying NP-CRNs during colonoscopy, one can assume that considerably more than 10% of NP-CRNs are currently being missed with even the most thorough conventional colonoscopic examinations. As NP-CRNs now appear to be significantly more likely to contain small cancers than are polyps, better and more specialized methods of colonoscopy may be necessary to reduce the chance that an early cancer within a small NP-CRN might be missed (and, for the record, virtual CT colonoscopy, which I have discussed previously in another column, cannot currently detect NP-CRNs). In addition to the greater challenge of detecting NP-CRNs, when compared to colorectal polyps, NP-CRNs that are identified during colonoscopy, and are amenable to removal with the colonoscope, may be more likely to be incompletely removed when compared to polyps.
Finally, due to declining reimbursements for colonoscopy, gastroenterologists often feel pressured to perform colonoscopy more rapidly than in the past, in order to increase their productivity. It has been well demonstrated that the more rapidly a colonoscopy is performed, the greater the likelihood that colorectal polyps will be missed. Since we know that NP-CRNs are considerably more difficult to detect than polyps, the implications of performing rapid colonoscopy are very clear: more NP-CRNs will be missed, even with the addition of new techniques such as mucosal staining, as GI doctors try to perform more colonoscopies per day to keep pace with declining reimbursements for their professional services.
Because of the many questions that this study has raised, I predict that it will eventually be viewed as a landmark cancer research paper, and its findings will stimulate a serious review of all of our current colorectal cancer screening guidelines. Currently, it is not clear if the general public is at the same high risk of having NP-CRNs in their colon and rectum (or the same risk of harboring colorectal cancer within NP-CRNs) as this selected population of veterans. But the provocative findings of this study will, nonetheless, have major implications on future colorectal cancer screening strategies for all of us.
HEALTH RISKS AFTER STOPPING HORMONE REPLACEMENT THERAPY (HRT)
I have written about the various findings published, over the past 6 years, from the landmark Women’s Health Initiative (WHI) study in previous columns. A new update, published this week in the Journal of the American Medical Association, sheds additional light on the long-term health implications of combination hormone replacement therapy (HRT), as taken by millions of women in this country, over the past 5 decades, for the symptoms of menopause. As I have mentioned before, the use of combination HRT has unequivocally been linked to an increase in the incidence of breast cancer, coronary artery disease (including heart attack), and stroke, among other serious illnesses. This new WHI study update takes a look at those women who stopped taking HRT when the WHI released its disturbing preliminary findings (and which resulted in the early termination of the WHI combination HRT research trial) in 2002. In this update, the health status of women who had stopped taking HRT medications for an average of 3 years is reviewed and analyzed. The results paint a mixed picture of health risks present even 3 years after cessation of HRT.
A total of 15,730 postmenopausal women were included in this analysis, and consisted of women who took combination HRT pills during the WHI study and women who took placebo (sugar) pills that appeared identical to the HRT pills. When the data was analyzed, the good news was that, at an average of 3 years after stopping HRT, the risk of coronary artery disease between the two groups of women had, once again, become equal. That is to say, the increased risk of coronary artery disease that was observed, during the WHI study, among the women randomized to receive HRT had declined to the same levels observed in the group of women who had received only placebo pills. However, unfortunately, the increased risk of developing cancer persisted in the group of women who had previously taken HRT pills during the study.
The overall cancer risk among the women who had previously taken HRT pills was 24% greater than for those women who had received placebo pills, although the total numbers of patients diagnosed with new cancers was still small (1.56% of women in the HRT group vs. 1.26% in the placebo group). In terms of breast cancer risk, specifically, there was a 27% increase in risk among the women who had previously been assigned to receive HRT pills, when compared to the placebo group although, once again, the absolute numbers were rather small in both groups (0.42% vs. 0.33%, respectively). While a “modest trend” towards decreasing breast cancer risk was observed, over time, among the women in the HRT group, even at 3 years, a significant increase in both the incidence of cancer and the risk of death (from any cause) was still present when compared to the placebo group of women. When the WHI study data was reanalyzed, 3 years after the women in the HRT group had stopped using HRT, the results indicated a persistent imbalance between the risks and benefits of combination HRT, with a calculated 12% increased risk-to-benefit ratio favoring risk over benefit.
Longer follow-up of the women assigned to receive HRT pills during this study will have to occur before we can learn when, if ever, the increased risk of cancer (and the overall increased risk of death from all causes) will return to the same levels as has been observed in women who never received HRT. Once again, my advice to women passing through menopause is that they avoid HRT if at all possible. For the couple of percent of women who have truly debilitating menopause-associated symptoms that do no respond to non-hormonal treatment, taking the smallest dose of HRT medications, and for the shortest possible duration of time, appears prudent.
TELEVISION, CHILDREN & OBESITY
By now, most of us know that increasing amounts of time spent in front of the television have been associated with increasing levels of obesity in children. Now, a new randomized research study, just published in the Archives of Pediatric & Adolescent Medicine, sheds new light on this topic.
In this clinical study, 70 overweight children, ages 4 to 7, were randomized to two groups. In the intervention group, television and computer usage was restricted, while in the control group, no restrictions were implemented. All of the children participating in this study were evaluated every 6 months throughout the 2-year study. Weight, height, body mass index (BMI), television and computer viewing habits, calorie intake and levels of physical activity were specifically assessed at these 6-month intervals.
In this small but innovative study, the children in the intervention group showed significant reductions in overall sedentary behavior, with increased physical activity and decreased calorie intake, when compared to the kids in the control group. When the researchers looked at socioeconomic status as a factor, they found that the children in the lower socioeconomic groups appeared to benefit to a greater degree from restrictions in television and computer usage than did the children in higher socioeconomic groups. Finally, when analyzing the data, the researchers noted that restricting TV viewing and computer usage resulted in improvements in the BMI of the kids in the intervention group, and that these improvements in the level of obesity were mediated primarily through decreased caloric intake, and not due to the increased level of physical activity also observed in this group.
In summary, this small randomized study showed that restricting the amount of time that overweight kids spent in front of a television and computer appeared to aid in weight loss, and that this benefit appeared to be primarily related to these children grazing on fewer calories while engaged in these sedentary activities. If your young children are like mine, weaning them from prolonged exposure to the mesmerizing effects of the hundreds of cable shows available on television is a huge challenge, but a necessary one.
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center
Send your feedback to Dr. Wascher at
Copyright 2008. Robert A. Wascher, MD, FACS. All rights reserved.
Dr. Wascher's Archives:
12-16-2007: Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality