The
information in this column is intended for informational
purposes only, and does not constitute medical advice or
recommendations by the author. Please consult with your
physician before making any lifestyle or medication changes, or if you
have any other concerns regarding your health.
FLAT
COLORECTAL NEOPLASMS
& CANCER
Colorectal cancer
is the second most common cause of cancer-related death in the United States. In 2008, an estimated
150,000 new cases of
cancer of the colon and rectum will be diagnosed, and nearly 50,000
deaths from
this disease are expected to occur.
As
I have mentioned in previous columns, colon and rectal cancers can, in
most
cases, be prevented or, at least, detected at a very early stage,
simply by
adhering to standard colorectal cancer screening guidelines (please see
my
1/7/2008 column for a more detailed discussion of current colorectal
cancer
screening guidelines). Currently,
colonoscopy, using a video camera mounted at the tip of a long flexible
tube
(endoscope), remains the gold standard for the detection of
premalignant polyps
(also called adenomas) in the colon and rectum.
While
the
majority of colon and rectal cancers that develop spontaneously appear
to arise
from premalignant polyps, which resemble fleshy protrusions sprouting
from the
lining of the large bowel, cancer has also been reported, much less
commonly,
to arise from lesions that have a flat shape, or even a slightly
depressed
appearance, with respect to the surrounding layer of tissue that forms
the
inner lining of the colon and rectum (the mucosa).
These less common forms of premalignant
colorectal lesions, often referred to as nonpolypoid colorectal
neoplasms
(NP-CRNs), were first widely
reported in
the Japanese medical literature, but were thought to occur only very
rarely in
western populations. A
new research
paper in the Journal of the American
Medical Association, however, suggests that NP-CRNs may not
be all that
uncommon in the United States
after all.
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.
To
summarize this important
WHI study update, the incidence of coronary artery disease associated
with an
average of 5.6 years of HRT use had, by the 3rd year of HRT abstinence,
returned to the level observed in age-matched women who had never taken
HRT. However, the
risk of cancer, and breast
cancer specifically, continued to be elevated, even 3 years after
discontinuing
HRT, among the women randomized to receive combination HRT pills during
the WHI
study.
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.
Disclaimer:
As always, my advice to readers is to seek the advice of your physician
before making any significant changes in
medications, diet, or level of physical activity.
