I'd like to get started.
We wanted to talk today about a
patient with Crohn's disease.
We asked Dr Sidney Barrett if he would
discuss this topic for us and this
patient dr barrett I
think many of you know dr barrett
is on our faculty
but is I started to say
stationed in roanoke but works in roanoke at the
Veterans Administration Hospital there.
And particularly many of the students have had an
opportunity to work with him at
Salem.
The patient will be presented by dr lois smith.
D.
W.
Is a 23 year old woman who began to have
blood tinged mucus or diarrhea at age
19.
Despite treatment with a Self Dean.
Diarrhea and cramping,
abdominal pain continued and a £20 weight
loss ensued Over the next three years.
She was first seen at the University of Virginia
Hospital in july 1975
at which time practice copy was unremarkable,
but X ray studies revealed an abnormal mucosa
in the terminal ilium and seek um with a stricture
of the mid descending colon.
The diagnosis of granuloma.
This colitis was made on the basis of the
history and X ray findings.
A sulfa Dean was discontinued because of a hemolytic
anemia which subsequently responded to
supplemental iron and folic acid
predniSONE 40 mg per day was given
for her colitis with clinical improvement and weight
gain complications of her disease
have included the following episodes
number one.
A left lower quadrant abscess
presented in october 1975 as an
abdominal mass.
Barium enema at that time demonstrated officials
tracked from the descending colon to the abscess
cavity treatment with penicillin and gentamicin
for two weeks and an increase in her pregnancy.
Own dosage to 60 mg per day
resulted in resolution of the mass.
In september of 75 she presented with a dry
scaly rash on her forearms and feet,
which was felt to be peligro.
This was a clinical diagnosis based on the appearance of the
rash and resolution.
After nice and supplementation.
Number three are three.
Ologists.
By March of 1976 her predniSONE had
been tapered to 15 mg a day and she
developed arthritis in both knees which were
partially responsible,
partially responsive to rest and solicited therapy.
Her present hospital admission on july the
12th was necessitated by three weeks of
increasing diarrhea,
fecal urgency and 10 isthmus.
She has had no fever,
chills nor recto vaginal fistulas,
drainage.
Physical examination revealed a thin
young white female in no apparent distress
temperature was 36.5 degrees centigrade.
Post 30 respiration 18 blood
pressure 1,
20/80 The skin was normal.
H.
E.
N.
T.
Examination revealed no evidence of your itis.
She was eventually,
however,
the chest was clear to percussion and ask rotation
and the examination of the heart was unremarkable
abdomen was soft to palpitation with no organa
medley nor masses.
The bowel sounds were normal.
The rectum was extremely tender to examination but with no
palpable areas of fluctuates.
The pelvic exam was normal.
The remainder of the physical exam was unremarkable
laboratory data,
hematocrit 47%.
White blood count 16,200
A wreath recite sedimentation rate.
50 mls per hour,
serum electrolytes and B.
U.
N.
Un remarkable serum protein
6.3 with albumin.
3.4 g percent uric acid,
7.9 mg percent alkaline
phosphate,
97 International units.
L.
D.
H.
1 34 international units.
S.
G.
O.
T.
20 international units.
X X rays will be subsequently shown
hospital course patient symptoms were
felt to represent exacerbation and rectal
involvement of her underlying disease.
Symptomatic treatment with six bass was
instituted after which she was able to tolerate a
practice practice ka pik examination on the
16th which revealed involvement of both rectal
and anal mucosa.
With March,
granularity and free ability and overlying
puss.
A sonogram performed on the 13th was negative
for any detectable abscess.
The dosage of predniSONE was increased to
30 mg per day and her symptoms
gradually improved.
She was discharged from the hospital on july the
20th.
Her discharged white count was
9500 with the urethra site
sedimentation rate of 34
fine.
Thank you very much.
Dr smith.
Any questions or comments dr
bolton.
Speak loudly
please
Not on this admission.
She has had that previously.
Yes.
Without any positive results dr
schafer you want to get set up for X rays?
I wondered what happened to her teeth dr smith.
Do you know what the occasion was that led to the
extractions?
I'm not sure I would assume.
Poor dental hygiene but it was not this
was not done in the last year too since the onset of her.
Not that I'm aware of
dr Whitby
when the diagnosis of the
niacin deficiency was made
Villagra.
Was she then continued on multivitamin
supplementation?
From then on.
Yes on her admission even she was on multi
vitamins niacin B 12 folate the
works dr barrett.
Has she been pregnant or tried to get pregnant any time during the
course?
No she has never been pregnant nor has she tried as
far as I'm aware.
Thank you very much.
Dr smith schaefer.
Okay I'm dr schaefer contrary to the
program that says dr
cooper we have the lights please.
These are films from the
upper G.
I.
Small bowel and colon examinations that were performed
in july 1975 approximately a year
ago.
And I'm just showing you here the proximal small
bowel which appeared normal except for the
presence of some dilatation of the bow
particularly.
I want to emphasize that the duodenum appeared normal
here.
We can see that there is further dilatation
more distantly in the genome but there is no
mucosal edema,
no strictures,
no evidence of involvement of the small
bow uh approximately.
We did notice that there was tremendously
delayed
transit time.
This is at three hours and still we haven't reached the
colon.
We're still in the terminal ilium and
it took 5 to 5.5 hours before we
actually reached the terminal ilium with
the barium.
These are spot films of the terminal ilium that show that
the caliber of the terminal ilium is reduced.
It's a regular.
The terminal ilium was spastic.
This is terminal ilium that we're seeing
here and here we noticed that there was some
Dema Dema speculation and there were
changes consistent with inflammatory disease involving the
terminal ilium.
The most spectacular changes though are in the colon that
were uh scene on the day before with the colon
examination
calling.
We see tremendous the regularity
of caliber of the bowel.
There was no evidence of abnormality on other
films uh in the region of the
rectum or sigmoid colon.
There was a very localized,
very narrow stricture in the proximal
descending colon.
Uh The area of the spanish lecture was
tremendously narrow and there was
another area area of narrowing over in the region of the
hepatic fracture with distension.
Here we see a post evacuation film that gives
us uh appearance here in the distal
transverse colon.
And I don't know whether you can appreciate it or not of both
longitudinal ulceration and transverse
ulceration here is a,
can you see that stricture in that film dr schafer
here is there is
a localized structure here in the descending colon
associated with what appears to be somewhat of
official ist track,
how common is that type of severe?
That is.
That is a severe.
Well now I see the lumen is uh I was looking at that
one thing on our left,
but the lumen is much wider.
Is that correct?
Could you point out the lumen of the bowel there at that stricture
point?
The Lumen of the Bowel is here and it is
approximately 2-3 mm
in diameter.
And how often do you see strictures of that severity?
And granulomas?
Uh enteritis involving the colon.
It uh it's more
common than we see in ulcerative colitis,
certainly.
And uh it's not a rare occurrence,
but usually we don't see such severe strictures on our
initial examination.
Usually we do see skip areas of involvement.
Like we see here,
we do see the longitudinal and uh
transverse alterations,
but we don't.
Normally,
at first examination see a stricture this
severity.
So these changes all fit most compatible e
with a diagnosis of brain alone.
This colitis by actually
fine,
thank you very much.
Uh This patient had to uh was ready
for discharge from the hospital on monday or Tuesday and
so she could not be here today and we felt that it was
not uh justifiable to try to get her to
come back.
So we made a brief uh film
uh a film clip to show you.
We could run that now.
Well,
Mr West,
thank you for coming over here today from the Towers,
we've talked for a few minutes.
You you call this problem that you have
regional regional enteritis is that you've
had this for a three year for three
years.
How was it initially diagnosed?
Well,
I was passing some blood in my stool and I went to an
internist and he did photography
and said that I had colitis.
Did you have you had diarrhea then?
Not really bad.
Just slight diarrhea.
Just the blood in my stool.
What's been the major manifestation of this
problem over this three year period?
The diarrhea and throwing up
vomiting.
And how severe did the
diarrhea get early On?
It got very bad.
I was going to the bathroom maybe 20 times a day
and you know,
just all the time I couldn't keep anything down.
And that you're when when things were really
at their worst.
You started predniSONE.
And was that did you attribute your improvement
to that medication?
Yes,
it seemed almost instantly I started getting better
less diarrhea.
And You had lost 20-25 lbs by
that time.
And you started to gain your weight and things got better.
Now have you continued on predniSONE since then for the
past 2.5 or three years?
Well I was on it for maybe a six month period and
then they took me off because I was doing well.
But then last july began to do the
same thing.
So after you stopped the pregnant sonia began to have a recurrence
of put me back on it and I've been on it ever since.
What's the dosage?
Well,
when I came in the hospital,
I was on 15 mg a day.
But now they've raised it to 30 to see if they could
probably what brought you to the hospital this time?
Well,
the diarrhea and I have some infection in my
victim.
It's very sore.
But you did you were having some diarrhea when you
came in this time.
That was sort of increase in
the severity of your symptoms.
How many stools were having a day?
Well,
that's six and very.
Did you relate that to anything other than
the fact that did you tell me that
there are certain times of the year when this gets
seems to get worse.
It seems like in the spring my two
major when it's hit me as being in
spring.
I don't know why it seems that way.
So,
did you actually have an infection in your
rectum this time or was that was an abscess or
No?
I don't have an abscess.
But they say from the disease,
they have some infection and your symptoms have
subsided since you've been in the hospital.
And they're better than they were when I can you attribute your
improvement to any specific
therapists,
they've been giving me a lot of sits baths and some
kind of suppository.
That does seem to have quite a bit,
I'm not sure what it is.
Have you had any other
complications from your from
this problem from this disease for the first time
I came back for my checkup I had
on my hands and my feet only it
was very puzzled by it because I only had
it on my hands and on and on my toes.
But they cleared it up very fast with vitamins.
And were you eating well then or was that related to
eating constantly?
When I started taking the presence on.
My appetite was very good.
But that was when your diarrhea was quite severe.
Diarrhea was subsiding too.
I thought I was getting better.
I was gaining weight when I came back from my checkup
but I had were you taking any supplemental vitamins
then?
No,
I don't think I was taking vitamins.
Thank you very much for coming over today.
Thank you.
Thank you.
I'm sorry about the focus on that.
Apparently there's some problem with the camera dr barrett
and this pilot?
Yes.
The movie that dr Mandel showed a couple of weeks ago was very
impressive with the white cells assassinating all the various bad
guys.
And I'm convinced that what the
gastroenterologist who talks about regional enteritis needs in order
to give a good presentation is a similar movie that
shows as a thigh,
a prion healing fistulas and predniSONE
license granulomas and the like.
But there is no such movie because we don't have any
information like that.
The story I'm going to talk about is the same
dismal story that you've heard in previous grand rounds
over many years about regional enteritis.
There are some interesting things on the horizon.
It'll be interesting in a few years to find out what
they mean,
where they fit into the whole picture.
For instance,
what is that uh side a
toxic effect of the illegal infiltrate
that occurs in cultures
of human colonic cells that looks exactly like viral
effects.
Uh why do the lymphocytes of patients with
Crohn's disease have a toxic effect
on human colon
cells and culture.
But we don't have any of that information today.
And I'm not going to say anything more about it.
I also don't want to talk anymore about the
extra intestinal parts of disease.
Except to comment on pila gra uh DR Hook
asked me to explain it and I certainly can't
uh in reviewing the literature,
I only find one case report in Dr bak
is textbook which candidates 1940
he shows a patient with a typical rash,
typical radiologic and pathologic findings and comments
no more about it.
I certainly can't explain this lady's disease.
What I would like to talk about are some of the
intestinal manifestations of the disease,
particularly some of the physiologic arrangements that
occur and what little we can do to redress the
balance and I'll have a discouraging word or two to say
about both medical and surgical therapy.
We have the first slide please crones
disease
can affect the entire gut all the way
from mouth to anus.
It's not surprising
if you think about it to
realize that the presenting
symptoms reflect generally the area of the ballot is
involved.
And as this slide reviews illegal
disease and proximal colonic disease of the
area's most frequently involved and
I will get back to those in a moment after making a short
digression to fill in this space between distal
ilium and seek them.
Yes,
science
patients who present with an
acute onset of cerebral illness and
right lower quadrant pain,
glucose psychosis are often judged on clinical grounds to have
acute appendicitis and indeed when they're operated on,
this is usually what they have.
But a minority of the time the surgeon will find
something else,
he may find just esoteric Adan itis,
he may find an acute inflammation
of just the terminal ilium
or
acute disease involving the terminal ilium.
If we can believe reports from Europe,
about 75% of this
group will have an infection that's
due to sort of tuberculosis
or politica.
This is an acute self limited disease in which no surgery
needs to be done.
There are no recurrences.
The minority will turn out to have an acute onset to their
Crohn's disease and will go on in the course of time
to develop the full blown manifestations of the disease.
The evidence that links yesenia
infection to these diseases consists of
culturing the organisms from the nodes and
illegal contents.
Not only that,
but the illumination titus to the
organism rise precipitously in these
patients,
you also need to know that if the disease does
turn out to be an acute onset of what turns out to
be chronic,
the organism cannot be cultured.
Nor is there any rise in illumination.
Likewise,
if retrospective reviews are made in patients who have
already established disease,
they have no um elevated titles
to use any organism.
Disease of the appendix uh is decidedly
rare as are these others.
Uh As I mentioned,
most of this data is from the european literature.
There are only a few scattered case reports in the United
States.
So it remains to be seen where in the total
picture of acute Crohn's or
also acute disease in the right lower quadrant
of the abdomen.
Where you see Nia Sioux,
tuberculosis infection fits in.
Let me turn now disease of the ilium and
colon.
There are too many numbers on this slide.
I just want to make several points.
The first point is that most
patients in this is typical of several
large series have small bowel disease,
either alone or in concert with disease.
In the colon,
the minority perhaps 10-20% have
disease of the colon alone.
And this makes an important differential diagnostic point
uh in making the
diagnosis of Crohn's versus all sort of colitis,
abdominal pain and diarrhea are almost
universal when illegal diseases
present,
weight loss is
often present.
Um and there are several points which I would
like to make about abdominal pain for moving on.
First of all,
when the disease starts and involves the terminal
ilium.
The pain is typically cramping and in the region
about the umbilicus,
this pain isn't relieved by defecation or
passage of flatness.
As disease in the colon often
is later on as the disease progressive
progresses and fiscally or
inflammatory masses are formed.
The pain may become continuous and move to the right
lower quadrant.
Next let me point out that anemia is present
almost half the time,
but that obvious bleeding
is less common,
suggesting that there are other factors involved.
And I'll come back to that.
Finally,
when patients with Crohn's of
the kolinahr granuloma colitis
only in the colon are compared to patients with
ulcerative colitis.
There are some differences which are worth pointing out.
First of all,
diarrhea is common to both,
but bleeding is virtually universal in patients with
ulcerative colitis.
Likewise,
rectal involvement is almost universal,
95%,
maybe too low a figure,
it is very difficult if not impossible to make a
diagnosis of all sort of colitis.
If the rectum is normal and when this
lady first presented,
it's my understanding that her rectum was not involved.
The last point I'd like to make here is that
periodontal disease is significantly
more common in patients with Crohn's or
granulomas colitis.
Uh and 70% maybe a low figure
this presents as officially or fissures in
the region and it's worth also pointing out
that these peri anal manifestations may precede
the full clinical picture by months or years.
In some patients,
the diagnosis will not be obvious.
They don't present predominantly with abdominal pain and
diarrhea.
They may have a variety of other clinical syndromes.
More than likely these clinical syndromes will
complicate established disease,
and I'd like to say a word about several of them,
about anemia,
about weight loss,
about urinary stones and
about gallstones.
This is a series of 63 patients who had
active Crohn's disease,
65% on investigation were
found to have low serum iron.
This probably resents the blood loss,
which is usually a cult uh iron is well
absorbed in the most proximal part of the gut
and usually I would expect it to be absorbed
normally.
However,
I have seen no data on uh
iron absorption studies in these patients.
It would not be surprising in today's patient to
find that she malabsorption iron since she did
have considerable abnormalities in the proximal small
bowel.
Next 22% had low iron binding
capacities.
Uh this may represent protein malnutrition or
it may represent uh the part of the anemia of
chronic disease 16%
had low B 12 and B 12
levels.
Most of these patients had
extensive involvement of the terminal ilium or had extensive
resection uh of the terminal ilium for disease.
They're a minority had various
strictures,
blind or variations on the blind loop syndrome,
in which overgrowth of bacteria bind the
B 12 and make it unavailable for illegal
absorption,
somewhat surprising is that
64% had a low serum foley.
This is surprising at first
glance,
because it is well absorbed in the proximal gut and
usually the proximal gut is not involved.
What is also more surprising is when they looked at
the extent of disease in their patients,
many of them had distal disease only know manifestations of
proximal disease.
However,
more recently,
it's been found out that absorption of label
folate is abnormal in most
patients with Crohn's disease,
regardless of whether they have
radiologic or even histological involvement of
proximal small bowel.
What is even more interesting is that a sulfa Dean
further increases the malabsorption of folate,
not only in patients with Crohn's disease,
but even in normal patients,
how this fits into the overall picture,
I'm not sure,
but it certainly is a warning that any
patient with crones disease,
mame al absorb folate,
albeit in subtle fashion and they
probably all probably ought to be supplemented with
folate and other vitamins as well.
Having heard that,
I suppose it's not too surprising to see that in this
series,
40% had a mega plastic anemia and most
of them turned out to be do uh two full
aid.
The minority to be 12 and a few were mixed
disorders.
Moving on now to weight loss
an intact ilium is necessary for
the neuropathic circulation of bile salts.
If the ilium is either
diseased or removed
assaults are lost,
this results in a decreased concentration of bile
salts in the proximal gut during
digestion.
Therefore the critical my seller
concentration of bile salts is not
reached and fat malabsorption of long chain
triglycerides occurs.
Therefore stool fat excretion goes
up and also because the
ilium is lost.
The Schilling test is abnormal.
Well,
it's easy enough to correct the loss of B 12 with parental
B 12.
But in order to correct the
malabsorption of fat,
one needs to give a diet that is lower in the long
chain triglycerides and supplement the diet
with medium chain triglycerides.
Portage in is one formulation of it,
which do not require my cells in
order to be absorbed.
A variation on this function of the
ilium is some sort of intestinal
stasis,
The common component of which is bacterial overgrowth.
And here bacteria in the proximal small gut,
the conjugate and di hydroxy lit
the bile salts.
Once again,
the critical my seller concentration of bile salts
is absent and fats are
absorbed and as I mentioned
earlier,
the bacteria compete for
B-12 binding it and making it unavailable for
absorption further on.
In this case,
the simple thing to do is to treat with
antibiotics,
which decreases the intestinal contents of
bacteria,
returning fat absorption to normal and returning
B-12 absorption to normal
when bile salts aren't
absorbed as in this situation
here,
I apologize for this slide,
They get to the colon
when they get to the colon,
they turned the colon from its normal,
efficient absorptive state into a secret
ori state.
And what I want to point out with this slide is
that this line represents zero flux of
water and electrolytes above indicates
absorption below secretion when the
bowel is refused.
First with electrolytes,
the net flux is absorption when
bile salts are added,
inhuman or in experimental animals,
net secretion is the result.
So the colon becomes
an organ which is contributing to the diarrhea.
The binding resin cola star mean,
will bind bile salts and will certainly decrease the
diarrhea.
Although this may be at the expense of increasing
Seattle area because if the bile salts are bound by the
coolest are mean,
they are not available for fat absorption.
The patient with Crohn's disease really can't win when it comes to
absorption
gallstones.
Uh bile salts are necessary
to maintain cholesterol in the bile in
solution when the ilium is
lost and bile salts are not re
absorbed.
The ability of the bile to hold cholesterol and secretion
diminishes.
Therefore,
cholesterol can precipitate and become the night is for
stone formation.
So we have an excellent theoretical reason to
suspect the patients with Crohn's disease involving the ilium
will have an increased incidence of gallstones.
Patients with Crohn's disease
involving or all sort of colitis involving only the
colon have an incidence of gallstones in this
series,
which is roughly comparable to the hospital
population.
Those with illegal disease.
Indeed do have an increased incidence of
gallstones.
The message here is to be aware that it
happens inflammatory,
rather inflammatory bowel disease is associated
with the syndrome of cola static liver disease.
The patient who has jaundice and elevated alkaline
phosphate case may indeed have
that form of perry cholangitis,
but on the other hand,
might also have a very treatable
form of disease gallstones.
Parenthetically,
I also ought to remark that on theoretical
grounds.
Coolest Ira mean,
which binds bile salts ought to predispose towards
the formation of gallstones over the long run.
But I know of no data to support this.
I would just be aware of it.
We're treating a patient for a long time with Co star
mean,
some arrows are missing on this.
The slide was made hastily.
You're aware of a number of renal
complications which occur in uh Crohn's
disease.
There can be fiscally from involved bowel to ureter or
to bladder.
There can be obstruction of the ureter by an abscess.
There can even be renal amyloidosis.
These patients also develop stones
which turn out to be in the main oxalate stones.
The current thinking on why they develop oxalate
stones is as follows in the normal
situation.
Dietary oxalate is
bound by calcium in the gut.
There should be an arrow here into an insoluble
precipitate and is then passed out in the stool
in the abnormal situation with illegal disease,
dietary oxalate and
calcium meet with un absorbed fat.
Harold here somehow
or presumably calcium
complexes with the fat oxalate remains
soluble,
is absorbed and excreted Greenlee,
where stones can form way to
attack this.
There are several plausible ways eat less
spinach,
decrease the dietary content of oxalate,
increased calcium so it'll bind the
oxalate.
One can also add aluminum to the diet,
perhaps in the form of something like an eagle,
which has also been shown to bind oxalate
or decrease the amount
of fat in the diet,
particularly long chain triglycerides.
All of these will decrease the urinary
excretion of oxalate
treatment.
Let me concentrate predominantly
on these last two sections.
What
by comparison in all sort of
colitis,
there is excellent data to indicate that
predniSONE is the best drug to induce a
remission of the disease in its acute phase
and that is alpha Dean is the best drug
at maintaining the remission.
Once it's gotten with predniSONE
in this disease,
whether of the large or small bowel,
there is no such convincing data,
although clinical observation for a long period of time
has led most physicians to use a sulfa
Dean as the first line drug,
particularly in a patient who wasn't specifically who isn't
terribly ill.
Give it a trial of a month or
two and then move on to predniSONE.
If the A's alpha Dean doesn't work or to use a sulfa Dean
in the sacred patient,
essentially unresolved are the two questions of
which is the preferable drugs in the acute situation,
which is the preferable drug in the long term
situation.
There has recently been an attempt to answer some of these
questions or at least to provide some data to provide the
rationale for therapy.
National Cooperative study of disease
addressed itself to both of these part.
One was an attempt to induce remission in patients
with active Crohn's disease.
238 patients with active disease
has defined by one of the references on
on the sheet were treated for four
months in double blind fashion.
With one of the four options I listed on the other
slide,
hazel thodin predniSONE is a thigh aspirin
and placebo results which were
reported last month and there are more patients to come,
so perhaps they may change no surprise.
predniSONE is superior to placebo,
is alpha.
Dean is superior to placebo.
This is what physicians have observed for a long
time.
Perhaps a little bit surprising is a tire print
was no better than placebo
dr Drucker of this institution published a report
about six or seven years ago and this was
also followed by others which indicate that
Prince had a place in the treatment of some patients
with active Crohn's disease.
Indeed,
one report suggested that fiscally
closed when a tire print was used.
This,
these previous studies were
almost all uncontrolled.
Now,
this study presents evidence that in a
controlled situation is a thigh prin is no better
than placebo.
It follows on the heels of another.
Another study,
also listed in the reference sheet,
which suggests the same thing.
The group at Yale took patients maintain them on their
usual dose of predniSONE and added easier
either as a prince or placebo
and studied the patients for four months at a time.
The groups then crossed over and
once again,
no difference could be found between and
placebo it seems
then as of now,
that is not for every patient with
crones disease,
there are a few in whom it might be tried.
For instance,
the patient who has is unable to tolerate high
doses of steroid.
It may exert a steroid,
quote steroid sparing effect.
It also might be used in a patient in whom surgery is
unacceptable.
There are those who still hold out and suggest that there is a sub
population of patients with Crohn's disease who
may benefit from a print.
But this sub population has yet to be
defined.
Finally,
let me turn to surgery and make several
points.
Once again,
the data are conflicting and even the most
optimistic results that you can find are none
too cheerful.
Several points.
First of all,
when disease involves a small bow,
basically there are two options to remove
it all or to bypass it in some fashion.
Usually the surgeon will remove it if it's technically
feasible.
This study is taken from the last reference on the
paper published in the new England Journal by
Janowicz group from out Sinai last year.
And it indicates that there is some
minimal data in favor of
resection.
That is that with the passage of time,
the cumulative recurrence rate is slightly less other
authors in their day to have a more
favorable swing towards resection.
But what should be pointed out is that whatever the
procedure,
the cumulative rate of recurrence when patients are
followed over the long haul is awfully
high.
The next point I'd like to make is
that again,
is that there is a lot of controversy over the
recurrence rate after surgery for Crohn's
disease.
When the data is analyzed
crudely,
it is indicated in most series
that the re
operation rate or the recurrent and recurrence rate diminished after
each successive operation.
This data is open to criticism and is
criticized in this paper because
it fails to allow for decreasing time of follow up
after each successive operation.
When this is corrected for
data like this appear and exactly the
opposite conclusion is drawn.
That is that after each successive operation,
the chance of another operation becomes greater.
The final point I'd like to make
about surgery is that there were several
reports in the early 1970s
concerning granulomas colitis.
Crohn's confined to the colon.
They suggested that the recurrence rate after
total collector me with Elias to me was
much better than any kind of surgery for Crohn's that
was confined to the small bowel.
And indeed,
that there was virtually no difference between the surgical
results in ulcerative colitis and
granulomas colitis.
The group of Mount Sinai,
which is Dr Kron's hospital,
immediately replied to this report by coming up
with 31 patients of theirs who had had recurrence
after total collecting me and Elias to me for
the colon.
And this is not their data but data from a similar
series.
Again,
both the patients with all sort of colitis in the
colon have had total collector me and Elias.
To me,
the group with all sort of colitis have had far fewer
operations and the cause
of the operation has
been predominantly recurrent disease
proximal that is in the small bowel and more
often in this group.
Elias to me,
reconstruction as somebody who
doesn't have uh the
long experience and expertise with disease.
I take data like this with
uh a note of caution.
The outlook for the patient with surgery
after crones after surgery for Crohn's
disease is certainly guarded.
Now,
it maybe there's data which I haven't sighted to
suggest that the course after
Crohn's confined to the colon is
better than confined to the small
bowel.
But it certainly cannot be said
as far as I can see that Crohn's,
which is limited to the colon has as good a prognosis
as all sort of
colitis patient with ulcerative colitis who has a
total collectively can virtually be told he is
cured.
No such guarantee can be given
to the patient who has had a collective
for Crohn's disease.
Let me mention one more point.
Uh it was my understanding but not confirmed that
pregnancy complicated uh this lady's course.
At one point,
you turn the slide off,
please.
Dr Crone has addressed
himself to this point and he finds,
first of all,
that about a third of patients
who become pregnant when their
disease is inactive will have an exacerbation during
that time again,
those who become pregnant while the disease is minimally
active,
about a third of those will have an exacerbation.
The majority,
therefore,
both in his series and in the more recent one and the
british literature indicate that pregnancy
can be safely undertaken in women
who are either inactive at that
point,
from the crones disease,
or only moderately active
If pregnancy can be achieved in a period of
active disease,
the chances of carrying the pregnancy
to a successful conclusion are considerably less.
It's also interesting to note in the
series,
uh published in the British Medical Journal two or three years
ago,
that the fertility of women with Crohn's disease is
considerably reduced and that half of their series of 80
women who attempted over a ten-year period to become
pregnant or unable to do so.
Thank you.
Thank you.
Sydney,
you characterized your presentation at the
beginning as the same old dismal story.
And I don't know,
perhaps,
perhaps it was the same story in some respects.
But I'd say that your presentation was notable
for its factual content and for its clarity And
thank you.
Are there uh comments or
discussions from the group?
Dr Durant is holding up his hand undoubtedly to
explain this occurrence of
yersinia infection.
Sorry.
No.
Uh to enjoy that very much,
said I'm sure we all did.
Uh but a couple of the
things that you mentioned,
one of them the your senior but the other the granuloma
tissue response that characterizes the
pathologic lesion in these patients uh raised
the question of these patients immune status.
Uh Can you comment on any information about their
immune status,
particularly cell mediated immune status or
energy?
I avoided that purposely because I find it very
difficult to in reviewing the topic to make
too much sense.
And if there's somebody who can make more sense out of it than
I can I would would welcome a comment,
dr bolton.
You asked a question in that area.
You want to comment or does anyone
No one wishes to comment on that or the other
doctor.
I wanted to to make a
comment and ask a question.
Said the
problem of regarding iron deficiency anemia.
Certainly agree with you that these people
typically do have anemia of chronic disorder
characterized by low serum iron,
unusually low T.
I.
B.
C.
The percentages that you gave more of them had
something like 40% at a low serum iron about
20% at a low T.
I.
B.
C.
But very often they may even be hipaa
chronic.
And then if you look at the bone marrow you will find storage
giant.
They tend to have thrombosis.
Itto sis along as another evidence of
inflammatory response and very often they are
not iron deficient.
Um I wanted to comment also
about the hemolytic anemia here which did seem to
be related clearly to a sulfa Dean
which does in some way produce oxidant
damage to the red cell,
produces Heinz bodies and results in
hemolytic anemia.
And I think the statement here that the hemolytic anemia
responded two supplemental iron and folate
probably should say that the anemia improved as
a sulfa Dean was withdrawn and possibly
there was a component of full A
deficiency.
Um I wonder about the pill
Agra whether or not this isn't like
what is seen with some patients with blind loop syndrome.
You characterized these patients
with Crohn's disease as being,
well they have components of the bacterial overgrowth
problem possibly with B 12 malabsorption
on that basis.
And when there's bacterial
overgrowth and I would have to go back to review the
biochemistry of this but I think that the
bacteria may do something to trip to
fame.
They certainly you get a lot of in Dole's Indal
acetic acid is excreted into can excreted in
the urine.
And I wonder if with some borderline
malabsorption of niacin.
Perhaps uh an effect on breaking down trip to
faint and the lumen of the gut that the
requirements are increased perhaps
uh in addition and that they developed Malaga
on that basis.
It's interesting that it's so rare that you
I think that's a logical Step
two Do I.
I just couldn't find any definite um
studies of particularly vitamin absorption
or of effects of
bacteria in intestinal stasis on
vitamin metabolism.
Now,
if you recall in talking to her,
I asked her specifically about that and it was she answered very
clearly uh that she was eating
well at that time and that her
diarrhea was not particularly severe at that time.
So perhaps some sort of intrinsic mechanism did what
would account for it.
Dr Owen,
I said I may have missed it.
But would you interpret this cooperative study to
say that nobody is going to be using a Visa thigpen anymore
for Crohn's disease?
And also uh since this is part one,
could you tell us what part two is going to be like?
Part two involves a two year
study in patients with inactive disease.
To see whether any of those
four possibilities will suppress
the recurrence of the disease.
And so the data is not available yet.
Unfortunately,
it's my understanding that has been deleted from
that group because of a high incidence of
side effects,
unusually pancreatitis has occurred in
four or five patients.
Uh and I believe it's been deleted on those grounds.
Uh no,
people will not stop using as a tire print on the grounds of the
study.
I think people still believe although they haven't been
able to prove that some people by
golly do get better.
It's just we're just not smart enough to define them.
I wanted to ask dr will be related to
the Himalayas.
Sis understand that the fact that
she did developed developed hemolytic anemia with a sulfa
Dean.
And I think dr Zirkle in
dr keeling agree with your comments about the
protocol.
But the fact that she did develop that
means that she's a rapid settle later
of the compound.
And how does that account for the Himalayas?
Sis I don't really know.
DR hook maybe Sid got his hand
up can answer that.
How that does all I can say is that there is an
effect an oxidative injury to the
hemoglobin molecule which forms Heinz bodies
which then leads to him policies in the
spleen uh presumably because of
increased resistance and lack of reform ability of the
red cell.
Nobody knows how it works even in ulcerative
colitis.
But good results
are best correlated
with blood levels of self appearing the sulfur
part of the of the molecule.
And side effects are best
correlated with the slowest settle later phenotype.
It's not a rapid,
slower satellites.
Right.
They have.
Does that mean that there will be a slower settle later
of for example,
supposedly holds true.
So it's added backwards I believe.
So the molecule is split in the
distal small bowel or large bowel
into self appearing and five amino
salicylic acid and after
being absorbed in the sulfur is then set elated.
And as I said,
high blood levels of sulfur occurring more often and
slower sata laters are associated with more side
effects.
Okay.
I wanted to ask you uh that second
slide where you showed a number of different conditions related
to things in the right lower quadrant.
I didn't quite understand.
Um you said
75% of something would be
explained by the larceny organism.
What of what is that?
The people of the non
appendicitis group obviously
uh those who have missing
pericarditis,
acute regional acute terminally itis
not Crohn's and acute Crohn's
but people presenting with with an
acute illness with right lower quadrant discomfort
and
if it's not you're a genital disease and it's
not typical acute appendicitis
then it's one of those
others,
the patients presenting with the syndrome of acute
appendicitis that don't turn out to have a large
proportion of them will have the Athenian.
If reports in this country bear out
what Reports carries.
I've been trying to recruit somebody down here to tell us more
about your sena uh dr Grant.
Do you want to did I succeed with you?
I suppose.
So uh you're saying it's certainly
uh recognized cause of
granulomas.
This disease in the terminal small bowel as well
as the peasant eric.
And notice that uh
further that said mentioned
uh there gram negative enteric bacteria
that really looked like proteus on
usual.
Something about you
language
try it
now.
The the
the organism is a non lactose fermenter which is
often missed in the routine uh
bacteriology lab because it's expected to be a
normal uh flora organism.
Uh It also uh
frequently will require growth that room temperature to
isolate it.
And it's been caused uh identified
increasingly in Scandinavian countries as a cause of acute
diarrheal disease as well.
Uh It's an interesting organism because it tends to
grow inside cells like
salmonella and indeed its path of
physiology may well be similar
to an invasive process that
gets inside cells and then is allowed to
survive.
Especially perhaps in patients with defective cell
mediated immunity.
Which is a good it would fit
well with the granuloma.
This process that we see uh that was why I asked the
question about that.
I don't know that anybody has looked at these people to find out that they
have indeed do have defective cell
community.
Have they?
I because they don't they don't,
go on,
go on to be.
Well uh let me make one
other comment that you raise.
That's very interesting indeed.
That is the toxic effect of illegal influence
uh from these patients.
Uh maybe due to a virus uh everything
seems to be uh incriminating viruses
these days.
But another possibility are the site of
toxic effects from products of certain
bacteria.
Shigella are fairly familiar to produce a site
of toxin,
but Clostridium preventions may also produce it
and goodness knows what other bacteria might produce.
Site a toxic products.
And uh I think that's certainly an area that we need
to look into more.
The idea of the virus I think is pretty tenuous at this point.
It's based purely on morphological changes in the cell
culture.
They look like it.
Therefore it must be dr arora.
See it's a very simple and I question I think
I'm very ignorant.
Why did you place right on the top of the list?
Low fiber diet.
Uh could you explain why do you
rational this particular diet for patients in
dr bak is textbook.
He has a long section on diet
which is I think very conservative and very
restrictive.
Most people don't believe or don't practice in
that fashion,
feeling that let the patient eat what the patient
will as long as it doesn't upset the car owns.
The only restrictions on this are patients with
genetic lesion strictures who will find
that increased fiber in the
diet causes more pain and
therefore they find if you don't tell them first,
but they ought to decrease the fiber in the diet.
Well,
Dr Stone is coming to the microphone.
I was surprised to see the uh the rectal
involvement at 50%.
I would have guessed that it would have been much lower.
The figures vary from,
I don't know,
25,
to 50%.
A couple of comments.
One question I get asked continually.
I'm sure you do too.
Is this disease increasing?
Are we seeing more actual cases or is it a question of
of our better diagnostic
capability?
And two,
what are your thoughts about the
the filter bubble agent which is being
now uh talented
perhaps uh playing a role in ideology?
Is this just a toxic effect?
Or is there a better evidence than that that it is a is
a living organism?
The answer to the first question,
I believe there is some epidemiologic
evidence to cite that the incident is indeed increasing and
equals that incidence of all sort of colitis
personal experience which is brief.
I've seen considerably more Crohn's than I have ulcerative
colitis.
I don't know what that reflects.
Uh One of the other
interesting things in the pathogenesis
is that material from human granulomas in the
intestine have been passed through a filter
injected into rabbit ilium and it produced a similar
pathologic picture and I believe this has been passed another
generation.
And what
I know about dr I know
you've seen this patient,
you interested,
you ever comment,
Sir Dr
Hunter.
Is there anything to be learned from
geographical epidemiology of this disease?
Does it occur all around the world with equal
frequency more common in whites than blacks?
More common in jewish populations.
More common in urban populations.
Um probably in Israel as well.
And other than that,
uh,
I don't think there are broad bands of geographical
involvement versus non involvement to suggest certain
viruses.
Are there other questions or comments?
Not.
Thank you very much.
Time's up.