- We went back and did this ourselves
in a pseudo-prospective way.
'Cause every study so far, in 5-ASAs, has done a
case control study, where they basically
just looked at people retrospectively.
What we did, was we tried to simulate a cohort design,
where we went back to the mid-1990s
and just took everybody who had
a colonoscopy in the mid-1990s
and follow them in a pseudo-prospective way
for about 10 years into the early 2000s.
And we saw who developed indefinite,
low-grade, high-grade, cancer.
We were able from their charts to see
whether they were on 5-ASAs, how much they were on,
did they stop taking it.
For each patient, we knew,
of course we didn't do pill counts,
'cause it was retrospective, but we knew
who was on 5-ASAs for how long.
We wanted to see if 5-ASAs work, where do they work?
Do they work for people who have no dysplasia,
do they work once you've already had dysplasia?
The punchline is that once you already have dysplasia,
they don't work, okay, you've gotta catch people
before they get low-grade.
We have some data I'll show you in a moment
that for people who had indefinite dysplasia,
although it wasn't statistically significant,
the people that were on 5-ASAs did not progress.
So maybe it works before you get dysplasia.
We don't really know this,
because you'd have to study thousands of patients.
We only had about 300 patients in the study.
This is the data from our study.
If you look overall at the progression
to any kind of dysplasia, or just high-grade or cancer,
we did not find a statistically significant lowering
of the risk to progression, whether you looked
at 5-ASA as any use, more than 2 grams a day,
or average dose over time.
We cut the pie up as much as we can.
There is a trend towards protection, granted, maybe a 30%
protection from going to advanced neoplasia,
but none of that was statistically significant.
At least from our pseudo-cohort design,
we're not sure that 5-ASA is all that protective.
But here are the patients who had low-grade dysplasia,
and we looked at those who were on high dose of 5-ASA,
meaning more than 2 grams a day or low dose.
And you can see that there was really not a big difference.
If anything, the people on high dose
5-ASAs progressed more than people on low dose,
but this was not statistically significant.
But if you catch people before low-grade,
if you look at the indefinite group,
this was kind of interesting to us,
we had 28 patients who had indefinite dysplasia.
The ones that were on high-dose didn't progress at all
in a long period of time.
The ones on low-dose 5-ASA were the ones that did progress.
Now, again, it wasn't statistically significant,
but it's kind of interesting.
Maybe it depends on where the person is in their disease.
And of course some of the great work that's been coming out
in the last year from Peter Higgins's group
is the cost-effectiveness.
How do we put together our knowledge of 5-ASAs
with our knowledge of surveillance?
In their well-done study, assuming that there's
a colon cancer incidence of 30%, which may be true,
maybe it's a little bit less than that,
and we can think that 5-ASA may prevent about 49% of
colon cancers, that's based on the literature.
Without using any 5-ASAs a colonoscopy every year
prevented 89% of colon cancers and cost about $69,000
compared to colo every two years.
But with 5-ASA surveillance might be able to be lengthened
and I think Peter deserves credit,
and his group deserves credit
for getting us to think about
can we integrate colonoscopy intervals
based on what medicines the patient is on,
and I think we need to see more data on 5-ASA
and how it might interface with surveillance.
Now, chromo.
Anybody here doing chromoendoscopy for,
I know you've done some great research studies,
looking in Lynch syndrome and sporadic adenomas,
but is anyone using it for IBD patients yet?
Peter is.
I ask this question wherever I go,
very few people are doing chromo.
You go to Europe, more people are using chromo.
You have to learn what you're looking at.
It is a bit of a learning curve.
It's not that hard to learn.
But unless you're wearing scrubs, you're gonna go home
and your shirt and your pants are gonna be blue
because it gets all over the room.
Okay, so with chromo, you can see these kinds of lesions
that, arguably a good white-light endoscopy
might have tipped you off that there might be something
going on here, but when you squirt in indigo carmine,
or methylene blue it usually highlights things a lot better.
These are the studies so far that have compared
chromoendoscopy to white light.
And realize that some of these studies,
because they're a few years old, may not have been using
the very latest high-definition white light technology.
But be that as it may, every study
has shown that you increase your pick-up rate,
your yield of finding dysplasia is three,
maybe even four times that of white light.
This is the only study from the US, it's Jim Marion.
At our medical center, we found the same thing.
You can find more dysplasias if you use chromo.
The problem is we don't know what that means biologically.
So you find more dysplasias.
It's almost to me like finding an ACF in a colon.
What are you gonna do, are you gonna take out somebody's
colon because you found an ACF, or two, or three?
We don't know what to do with the information and in fact
when I ask the gurus in the world,
Ralph Kiesslich and Brian Saunders,
there have now been a handful of patients worldwide,
maybe about 10 or 12, that have gone to colectomy
because, purely because chromo
found more dysplastic lesions, and not one cancer
has been found at the time of colectomy.
The people who do chromo say that's a success.
'Cause we prevented cancer from happening.
But if you're the patient, you might have kept your colon
another few years, a colon is a handy thing
to have around the house, so it depends
on how you look at that data.
We don't know whether we're changing the natural history
based on chromo.
Peter, again, his group has done a nice job of helping us
model this, understand this, because basically what this
study did, was it's asking what percentage of the colon
has to be dysplastic for you to pick things up
by random biopsy or by chromo.
And what you can see here is that to detect dysplasia
affecting at least 5% of the colon,
I think 5% is probably a reasonable pick-up rate,
32 random biopsies, which is around
what we recommend these days,
provides only about 80% confidence
that you're gonna find that 5%.
You have to do 45 to 58 biopsies
to get up to 90% or 95% confidence.
Nobody takes that number of biopsies,
I'm telling you right now.
Even at Mount Sinai, where we study this,
we're not taking that number of biopsies.
In fact, studies have looked in the US and Canada,
in Europe, most physicians take less than 20 biopsies,
so we only have about 60% confidence
that we're finding dysplasia.
So to achieve a dysplasia detection threshold
equal to enhanced endoscopy, equal to chromoendoscopy,
with 90% confidence would require taking
4,690 random biopsies.
(audience laughs)
Everybody go ahead, you go out there and do that.
And the point is, enhanced endoscopy
can detect much smaller dysplastic fields.
It makes sense, you're squirting in dye,
you're finding things, but what we don't know
is the effect of that on cancer progression or cancer risk.
So right now these are the guidelines that we still live by.
They didn't really change significantly
when we put out this technical review last month.
Basically if someone has no dysplasia,
you have them come back in one or two years,
if there's indefinite, you want to intensify
the surveillance a little bit more frequently.
If there's low-grade or high-grade and a raised lesion,
and you've completely removed that lesion,
you biopsy the base and you biopsy everywhere else
and there's no dysplasia,
that person can remain in surveillance.
You'd have them come back probably in three to six months.
If you have high-grade in a flat mucosa
or low-grade in a flat mucosa,
most people would recommend a colectomy.
But again if you have low-grade and flat mucosa,
most patients, unless you tell them
there's a 73% chance that they've got cancer there,
they wanna stay in surveillance
and you have to keep following them closely.
We usually begin at eight years of disease.
We don't care whether you've only had left-sided
versus pancolitis, the old recommendations used to say that
you wait for 10 or 15 years of duration.
If there's only left-sided disease,
we tell everyone other than those with proctitis
to start at eight years.
With PSC patients, the moment you diagnose PSC
you gotta do a colonoscopy.
That's when their meter starts.
We repeat colonoscopies every one to two years,
you might want to shorten the interval
if there's active inflammation, if there's a family history,
if there's PSC, if these anatomical
abnormalities are present.
You wanna take representative biopsies
from each segment of the colon.
You can do chromoendoscopy if you have the expertise,
it's not mandated in the new guidelines,
and you wanna pay attention to raised lesions.
And do for Crohn's what you would do for UC.