- [Instructor] There was no difference in the rate of
permanent stomas, and some suggestion
the quality of life was better with a segmental colectomy.
So, for patients with proximal disease,
we would - an option is segmental colectomy.
There certainly would be reason, area for discussion
about doing the subtotal or abdominal colectomy.
Patients with distal disease almost
always need a total proctocolectomy.
Rarely, there's a patient who only has distal disease,
in which an abdominoperineal resection
with a colostomy is appropriate.
And in a controversial way would be
to consider an ileoanal reservoir.
And the final area that I'm gonna talk about
is Anorectal Crohn's disease.
You all know that this is a frequent and significant
problem. About a quarter - in population-based studies,
about a quarter, almost a quarter of patients
with Crohn's disease develop perianal fistulas.
The AGA has classified these into simple and complex.
Basically, if they're low, they have
only one opening and there are no associated problems
they're simple; if they're higher, are more complex
in terms of involving the vagina or having an
associated stricture or active rectal disease
they're considered complex.
Surgeons use a different classification, based on how much
of the sphincter muscle is involved; so that these perianal
or intersphincteric fistulas that involve very little of
the internal - of the total sphincter muscle; this is the
internal sphincter and this is the external -
we consider simple and low.
If they involve a significant percentage of the
external sphincter, that is considered a
more difficult problem and labeled transphincteric.
Our goals in taking care of these patients,
in an ideal world is closure of the fistula;
it certainly is to control sepsis and symptoms;
and to preserve continence.
So, for low fistulas,
that are more simple ones in which there's very little
muscle involved, we can do a simple fistulotomy, so this
would have been the external opening, here's the anus,
and there's just a small band of muscle, and that
can reasonably safely be divided with little consequence.
There are 21 studies that were reviewed doing fistulotomies
for low fistulas in patients with Crohn's disease
and there is a significant healing rate, and this is -
13 out of 21 have 80-100% healing rate, which is excellent
and hard to achieve in patients with Crohn's disease,
so it's a good operation from the point of view of healing.
However, there was a wide range of incontinence reported
and I think it requires very careful judgment about how much
muscle is actually involved if you're going to consider
doing a fistulotomy, and in some series a very high rate of
these patients came to proctectomy
or long-term diversion anyway.
The more difficult problem is what to do with the complex
fistulas, the patients who have multiple openings,
this person has - to orient you this is the anus -
this is a more chronic fistula, there's pus draining
here from an abcess cavity.
This is an older series
that looked at fairly standard treatment of treating people
with drainage of the abcess or perianal sepsis and inserting
a seton. This was done before infliximab or other biologic
therapies were available, and while that operation has been
thought to be controlling clinical symptoms for the majority
of people, the fistula healed or was quiescent in less
than half. Almost half required another seton,
so clearly the perianal disease was progressing,
and 15% required proctectomy. So there was a big room
for improvement. So what are the options?
This is - you all are I'm sure very aware of the medical
options, I'm just going to very quickly go through these -
one that's been used and studied is
metronidazole in particular but antibiotics in general,
there are no controlled trials showing that antibiotics are
effective for fistulas. There are some uncontrolled trials -
this is one looking at the use of metronidazole,
21 patients, 18 were maintained long term on metronidazole,
there was decreased pain and tenderness in all,
and in this series about half had complete healing;
another follow up study looked at 25% of patients,
when the dose of metronidazole was decreased
all the patients got worse so they clearly
had to be maintained. If it was restarted, not all improved
but a substantial percentage did. 16 of those patients
received the drug for over a year and half of them remained
healed. The problem is, another half developed paresthesias,
so there's clearly a down side to
long term use of metronidazole as you all know.
Because of those side effects, Cipro is often used,
however there's very limited to no data about the use
of Cipro and its success rate in treating perianal fistulas.
Azathioprine has also been looked at, this is a
meta-analysis, it's now fairly old but looked at
fistula closure as - which was usually reported as a
secondary outcome in these studies, and there was
certainly patients with given azathioprine did better than
patients on placebo and half of them it healed.
They took about three months to close, maybe a little bit
longer, and again there were significant adverse events
associated with the use of azathioprine in this
subset of patients.
The study which sort of changed the
face of treatment of anal-rectal disease or fistulas disease
and perianal Crohn's was this study which I'm sure
you're all familiar with; the - in that group, 68 - in that
study 68% of patients received a 50% reduction in
draining fistulas, and 50% or 55 demonstrated closure.
This is really the number we're interested in, I think
patients are... they're happy to have somewhat decreased
drainage but what they want is to be done with it.
The mean duration of closure in that study,
and those patients were just given the three doses,
was only 3 months, and 11% of them developed
a perianal abcess. The Accent II trial looked at - and this
is designed so that the patients who responded initially
to infliximab were then randomized to either get ongoing
infliximab or placebo, and you can see that there was a
significant rate, a better response, be there just in
fistula response, and again this is the standard of
decreased drainage, and in complete response, there was
an improvement in the patients who had infliximab.
So the question is what's happening in those patients?
Is it just that the drainage stops or are they
really healing? And there are now multiple studies published
using MRIs and ultrasounds that show that in most patients
there is a persistent tract underneath the skin.
That they may not be draining or may not be symptomatic
but the tract persists, which fits with the fact that most
of these treatments have required ongoing maintenance
therapy in order to keep people asymptomatic rather than
achieving a status of being healed and being
able to come off the medication.
So, maintenance therapy is often necessary. There are
problems with this that you all are more aware of than I am,
that antibodies develop; that immunosuppressive therapy
in addition to the infliximab seems to reduce that rate
of antibody formation, but the therapy is expensive.
And I don't know about you, but I certainly have
encountered patients who have come to me and say,
"I can't take that drug because I can't afford it."
So their kind need a surgical option.
Another option that's been looked at is cyclosporin,
there are no controlled trials that show that cyclosporin
is effective for perianal disease, there are 10 uncontrolled
studies with a significant response rate. This is typically
IV cyclosporin that was converted to oral; however,
there's a very high relapse rate when
the oral medications are stopped.
Tacrolimus has also been used in one randomized controlled
trial at the Mayo clinic; then 46 patients with fistulas,
43 of them - so the majority - were perianal. Again this is
looking at that standard of a closure of 50%, which I think
is quite hard to measure, they did find by that standard
a significant response rate to the Tacrolimus. However,
when you looked at closure there really was no significant
difference between the placebo and the drug.