- [Announcer] This program is brought to you
by the University of Michigan.
For more information, visit umich.edu.
- [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.
- Well, it's great to be here,
and as Peter was introducing me,
I heard days are numbered and tornado in the same sentence,
and then my name, so I'm wondering what that all means.
Hopefully that's not gonna portend anything going forward,
but thank you for having me here,
and again, to Peter, thank you for inviting me.
I was able to take a tour of your facility yesterday,
and I was impressed how big, I thought Pittsburgh,
how big Michigan is, so truly an impressive place
with a lot of buildings, and more buildings,
I understand, underway.
So as Peter said, and hopefully,
I don't know if people can see this,
but Peter mentioned I'm gonna really cover the aspects
of post-operative Crohn's Disease,
mainly from a clinical standpoint,
but in my last slide I will mention some of the
interest we have in looking at genetics, the microbiome,
and some of the physiology of post-op Crohn's.
We actually just assembled a group last week
at our university, and we're planning to put in
a U award for post-op Crohn's
and a natural course of disease
that has nothing to do with treatment.
But today, I'm gonna focus more on the clinical aspects.
Let's see, huh.
For some reason, let's see.
Hopefully I don't have to do this for every slide.
Yeah, that's, that's what's not working.
Um, and again, okay, there we go.
For some reason it seemed locked up.
So I think that all of you are familiar
with these treatment paradigms
for inflammatory bowel disease
where traditionally the medicines
we had used at the lowest part of the pyramid
were what we considered the safest treatments,
and then we went up to more aggressive immunomodulators,
anti-TNFs, and then surgery was on top.
Interestingly, one of the aspects that we're now looking at
for a defined group of Crohn's patients
is maybe we should be going to surgery
earlier in their course.
Maybe their disease, by the time we meet them,
is too far gone in terms of stricturing and fibrosis,
that actually inverting the pyramid
and starting with surgery may be more relevant.
We're not there yet.
There is a German study actually looking at this.
We have a small pilot study looking at first onset
of treatment being surgery,
followed by different parameters of medicines,
whether it be anti-TNF or immunomodulators after.
I really hope I don't have to do this the whole time.
I apologize.
The question is whether or not our increased use
of immunomodulators and anti-TNFs has decreased the need
for surgery over time.
And there are limited prospective data,
and we do have a couple of retrospective studies
looking at this.
You're probably familiar with the study
out of Paris that looked at the impact
of increasing use of immunosuppressive therapy
in Crohn's disease and intestinal surgery.
And without going through the study too much in detail,
what this group found is despite the increased use
of Imuran and 6-mp, there was still a high rate of surgery.
We actually published our data last year
looking at small bowel resection rates
in a similar cohort, but also included anti-TNF therapy.
And we collaborated some with Mt. Sinai in New York as well.
And we looked at nearly 3,000 patient charts
for patients with Crohn's who underwent surgery.
We included all the typical medicines that you would see
as far as treatment for IBD,
looked at disease behavior,
and then broke these down into different cohorts in time,
from a 1995 cohort up to 2007.
And what we found is that the time periods,
or each bar across the bottom,
you can see 5-ASA, immunomodulators,
anti-TNFs and corticosteroids on the far right,
and as you can see, and not surprising for those physicians
treating IBD is that there is an increased use
of immunosuppressives and anti-TNF over time.
And somewhat of a flattening or a decrease
in 5-ASA and corticosteroids.
So our question was, were we seeing a different rate
of surgery in these patients receiving
more immunosuppressive therapy and anti-TNF
at the University of Pittsburgh.
And interestingly, at least based on our study,
we did not find that the increased use
of anti-TNFs and immunosuppressive therapy
made a change in the outcomes as far as rates of surgery.
Now one very important caveat is that
part of this may be limited in the time
by which immunosuppressives and anti-TNFs were started.
Meaning that, if the disease is too far gone,
surgery's probably inevitable anyway,
and I think as we look at the data
in natural course of Crohn's disease,
that's an important factor to keep in mind.
Nonetheless, we found that the surgical rates
were fairly flat across time.
So what does this mean?
This means that, at least right now, in 2011,
despite IBD medicines, still nearly two-thirds
to three-quarters of our Crohn's disease patients
will undergo a resection in their lifetime.
Those are data that have been well-published
even in recent natural course of disease studies
from large centers and is something that we've seen as well.
We know that surgery is not a cure.
These are data by Paul Rutgeerts and other
from the early 1990s, where we know that
if you do nothing at all, you take a patient
who undergoes a resection,
they have a ileocolonlic anastomosis,
so the slate is wiped clean,
they have no active Crohn's disease,
and you do nothing else, that in three years,
30% of patients are starting to manifest symptoms
of Crohn's disease, and that by 10 years,
nearly two-thirds of the patients are having symptoms.
Somewhat alarming is that,
based on how the endoscopic appearance is
after surgery, nearly 90%, 70 to 90% of patients,
one year after surgery, will have endoscopic recurrence.
They may not feel this,
and I'll come back to this entity
of clinically silent Crohn's disease,
but the endoscopists in the room know
that if you have a patient with an ileocecal resection
and anastomosis, usually there's a honeymoon period
up to five years where they feel absolutely wonderful.
But, if you do a colonoscopy,
look at their anastomosis and neoterminal ileum,
there's a surprisingly high rate of ulcers and inflammation.
Probably even more surprising,
and this was again based on the Belgium data,
is the histologic recurrence occurs as early
as one week after surgery.
And there are some fairly elaborate studies,
which I won't go through, but in essence,
what they looked at is the neoterminal ileum
above an anastomosis, taking biopsies,
and finding that as early as one week
after an anastomosis, there is already Crohn's
that's starting to recur.
So patient may not feel it,
we may not see it early,
but there's already Crohn's disease occurring.
And this is getting into the whole interest
we have in linking genetics with microbiome,
and this is the big grant that we're putting forward
for our post-operative model.
Well, again, coming back to Paul Rutgeerts data,
can we predict which patient will have Crohn's disease
and complications of Crohn's disease post-operatively?
And in essence, he came up with a scoring system
that I think most of us in IBD are familiar with
as far as looking at post-operative recurrence.
And in his study, he took patients who had an anastomosis.
One year after surgery they underwent a colonoscopy,
and then they came up with a score from zero to four.
In essence, a zero is normal, one is less than five ulcers
that are seen in the neoterminal ileum.
Two is more than five, and then three and four,
more significant inflammation and scarring.
What was then done is he looked at what happened
to these patients who had these degrees
of inflammation then long-term.
And these are just to show you some of these scores.
For those that are involved in the prevent study,
you've probably seen these before
as examples of some of the scores that we use.
So on the top, it would be a score of a one.
So less than five ulcers in the neoterminal ileum.
A zero would be completely normal.
Three and four, I think, most of us are familiar
with seeing this in patients,
not just with surgery, but Crohn's disease,
would represent what we would consider
more moderate to severe.
And certainly that bottom one, the four,
we can start to see that there's already stenosis.