- [Narrator] The University of Michigan division
of gastroenterology
and the inflammatory bowel disease program hosts
the IBD visiting professor lecture series
in Ann Arbor, Michigan.
This series presents the latest in clinical research
and basic science from IBD experts from around the world.
- So we're gonna cover the magnitude of the risk.
We're gonna talk about risk factors.
Does surveillance colonoscopy work?
We're gonna talk about managing polypoid
versus flat dysplasia.
The management of, the natural history ,
this is a really bit of a moving target,
but we'll try to make some science out of it.
The effectiveness of chromoendoscopy.
The impact of chemopreventive agents,
surveillance recommendations at the end
and if there's time, at the end,
I'd like to share with you some of our
most recent data that's gonna be presented
at the oncology plan recession on distal dysplasia
being a risk factor for progression
to high grade and cancer.
So what do we know about the overall magnitude
of colon cancer risk?
Now we know that the lifetime risk
of getting colorectal cancer in FAP, is about a 100%.
With Lynch Syndrome, depending upon which gene you have
that's mutated, it's maybe 60 are 80%.
If you have IBD, it's about 15% lifetime or so.
So that makes IBD probably the third highest risk group
for getting colorectal cancer,
at least based on historical data.
So much of our understanding of how the time course
of that risk is, is shown in Jayne Eaden's meta analysis,
where, as we know, you don't typically find cancers
arising for the first decade of disease.
But after that 10 years of disease, it starts going up.
And patients look at this graph and they freak out
because it looks like it's gonna go up to infinity,
I'm destined to get colorectal cancer.
But look at the axis here, after 30 years of disease,
your probability is still only about 20%.
So it does go up, we used to think it was about 0.5 to 1%
per year and that's what we often tell our patients.
Unless you think that Crohn's Disease is any less
of a risk, you can get an almost superimposable
graph for people with Crohn's colitis.
This occurs if you eliminate people
who have just pure ileitis.
So if you only have ileitis, your risk of colon cancer
is no greater than the general population.
And, in fact, you have to have enough colon involved.
If you have a tiny little sigmoid inflammation
from Crohn's Disease, that's not gonna give you
all that much cancer.
So if you have substantial Crohn's colitis
for a comparable extent as somebody with a UC,
your risk is thought to be about the same.
So Jayne Eaden published her meta analysis in 01
and you can see here that at about 30 years of disease,
you got an 18% risk.
Subsequent to that there several
other population-based studies
that show that maybe dysplasia risk
is a lot lower.
In fact, you can see here from different parts of the world,
even after 30 years of disease,
we haven't even broken the double digits.
So that was kinda sobering.
Maybe the risk is not quite as high as we used to think.
And then Ed Loftus pulled a lot of this together
and also showed that the annual incidence rate,
it wasn't even 0.5% in many cases
it was even much less than 0.5% per year.
And, in fact, if you look at the relative risk
compared to the general population,
in some studies this was not statistically significant.
The Charles Bernstein study in Canada showed that UC
and Crohn's patients had about a two or threefold
greater risk than the general population.
So we're living with data that's somewhat conflicting.
What is the actual annual risk of getting colon cancer,
what is the overall lifetime risk?
We still feel, I think nobody would feel comfortable
so that we don't have to worry about IBD patients.
They're still a higher risk group.
So we have to come and manage them
at least based on historical data.
I just would point your attention in the back,
you may not be able to see, it's at the bottom,
but a technical review on this whole topic
just came out in Gastro Last month,
in the February issue of Gastro,
that Frankfort Lee, Rob Arts,
Jayne Eaden and I co-authored.
It's a bit of a long document.
Some of my colleagues at work joked
that it's gonna be a nice coffee table ornament,
that nobody's gonna read it
because it's like 40 pages long or something.
But anyway, anything that I say today,
if you all asleep or have to leave, it's in that document.
So, the most important risk factor we feel,
is having disease more than eight or 10 years
and extent of colitis.
Although this is based in large part
on old barium enema data,
if you've only had cholangitis in the extent
of your disease, you're supposed to be
at no greater risk than the general population.
But the more colon that's involved, the greater the risk is.
Of course we know that people of PSC
the seven or 5% of IBD patients who have VSPSC.
They're at very high risk of getting colorectal cancer.
Which is kind of curious because very often
their colitis is subclinical, it's very indolent.
Family history of colon cancer,
just like in the general population,
will increase your risk and the younger
the individual in the family is,
the higher your risk is with IBD, although,
again, that's based on very little data.
The issue of inflammation is interesting.
Until just a few years ago, this had not been looked at.
Now there's several studies.
There's a few that have looked at histology
and a couple of other have looked at colonoscopy.
However you measure active inflammation,
that does beget a higher colon cancer risk.
That doesn't mean that you have to have active,
you know, hamburger meat colonic mucosa
for 20 years, in fact, maybe there are people
who have just a horrible onset of disease,
the first year or two of their colitis
and then it burns out and lo and behold,
20 years later they got their cancer.
Should point out that one of these studies
came from our group and the person who led the study
was (mumbles) Bonsell Who was a University
of Michigan medical student who spent a year
with us doing the Doris Duke Clinical research fellowship,
so we're proud of her.
Now, anatomical abnormalities also had not really
been appreciated fully until recently.
We now know that if you have a diseased-looking colon,
you know we've all seen these colons,
if it's foreshortened and it's strictures,
if there's pseudopolyps, not only does it make it
harder to survey, but we think that each of these things
is a sign that there's been a lot of inflammation
in the past that has healed and that's probably
the risk factor.
But clearly dysplasia is the marker that we worry about
the most because that clearly puts somebody
on the path to cancer.
Those are the factors that increase risk.
What can lower the risk?
Well, surveillance colonoscopy is really what we rely on.
I'll spend a few minutes later talking
about chemo prevention,
the data's kind of mixed in that.
And there's even some data to say
that regular doctor visits actually lowers your risk.
What it is about that doctor's visit, I don't know,
maybe paying the bill more frequently,
lowers your risk.
I think what it is is that somebody
is actually reporting symptoms a little bit more regularly,
and that triggers a colonoscopy and there you go.
So we have to understand the level of evidence
that this technical review was based on.
It was actually, there's no randomized studies,
as you can imagine.
You're not gonna take an IBD population and say,
"Okay, half of you are gonna get colonoscopy
"and half of you are not and we'll see who gets cancer."
So, there aren't even any cohort studies.
So everything is case-control or decision analysis.
Its piecing together data as best we can
from the literature.
But when we look at the, when we look
at screening colonoscopy, or FOBT or sigmoidoscopy,
the gold standard to say that a screening
or surveillance test actually works,
is to say that it actually lowers mortality.
You can't just say that you're finding more cancers,
because all the cancers you were found are stage four,
your modality is useless.
You have to show that you lower mortality.
And we don't have that data and this is kind of
the best that we have.
Winston Churchill said, "Democracy is the worst form
"of government, except for all the others."
so we live in an imperfect world when it comes
to surveillance, but the one study,
there's really one study, that has shown
that surveillance colonoscopy lowers mortality
and you can't compare (mumbles) group at the Karolinska,
where in the case-control study design,
they had 40 patients with, who died of colon cancer
in UC and matched them into 102 controls,
and believe it or not, in those days
people were not getting regular colonoscopies.
They were getting barium enemas primarily.
So if you take and compare to a group
that never had colonoscopy, even having one colonoscopy
in the course of your colitis, will more than
lower your risk of dying from colorectal cancer.
Now the naysayers say well, yeah,
but that was not statistically significant.
But it still looks like an impressive reduction
in mortality and we use this, basically, to tell patients
that we think that what we do for surveillance,
is gonna save your life.
Can we lower the incidents, not just the mortality,
but the incidents?
Here too, there's basically only been two studies.
And I highlight them here.
There's one from England, which is in white
and there's one from the Mayo Clinic
which is shown here in purple.
They showed almost identical things.
Compared to people who never had a colonoscopy
in these case-control studies,
those who had a least one colonoscopy
significantly lowers their incidents
of developing colorectal cancer.
So, we do believe, that by doing colonoscopies,
and, as you know, we do them every one to two years
after eight or 10 years of disease,
we think that that actually is lowering the incidents.
For all we know maybe those numbers I showed you earlier
on where the incident rates have been going down,
maybe those rights are reflecting the efficacy
of colonoscopy or five ASAs or early colectomy.
It's a little bit hard to say where that's all coming from.
Let's understand a little bit
about polypoid versus flat dysplasia.