Hello and welcome.
In this talk,
we're going to cover gastric carcinoma,
cancer of the stomach.
Let's talk about
So although it is clearly not the
most common malignancy in the world,
it is the third most common cause
of cancer related death worldwide.
So it is a bad actor.
If you have gastric cancer,
that's not usually a good prognosis.
There is, interestingly enough, a higher
incidence in certain parts of the world.
This is not uniformly distributed around
the world, although, as we'll talk about,
some of the causative factors
are relatively common,
such as Helicobacter pylori.
But it's more common in eastern Asia,
and Eastern Europe and South America.
Some of this is
related to genetics.
Some of it is related
to dietary commonalities
in terms of what gets ingested,
such as nitrosamines and food.
And some of this is related to
infections, common infections,
such as Helicobacter.
Overall, gastric cancer occurs more
frequently in men than in women.
And the reasons for that
are not exactly understood.
The median age at the time of diagnosis
is usually in the seventh decades.
So typically, older individuals,
men more common than women.
The majority of the
cancers of the stomach are
going to be Adenocarcinoma.
So these are big
gland forming cancers.
There can be two types.
One is the intestinal type,
which tends to be nodular and quite focal,
that's the majority 70% or so
of patients will have that.
And the typical location for
that is down near the pylorus
in the antrum of the stomach,
although it can occur in other places.
That's going to be the one that's
more common in men, older age groups,
and lower socioeconomic classes probably
related to infectious etiologies,
again, such as Helicobacter.
There's a second type, which is about a
third overall of these Adenocarcinomas.
And that's going to be
the linitis plastica type
that's literally translated
as a leather bottle.
I'll show you what that
looks like on the next slide.
This has an equal
and it tends to be a much more
infiltrative diffuse tumor.
So it doesn't have
It's kind of diffusely
And it's more common
in younger age groups.
So that's kind of
There are other cancers that we're not
going to spend too much time talking about
that's about 13% of the overall
gastric cancers are actually lymphomas,
not epithelial malignancies,
The stomach is the most common
extranodal site of lymphomas,
that's because there's lots of
inflammation in the stomach.
And with driving inflammation, we will have
local nodal hyperplasia of lymphocytes,
and they may acquire over
time certain mutations
that allow them to become mucosal
associated lymphoid tissue tumors
or MALT lymphomas.
Those will transform eventually
to a large cell lymphoma.
The MALT as you might expect,
is associated with inflammation
not otherwise specified,
but specifically with
which drives a very prominent
And then there are the non-epithelial
non-carcinoma gastric cancers,
such as the gastrointestinal
stromal tumor or GIST
which is about 1% of
primary gastric cancers.
This is a tumor of the cells
interstitial cell of Cajal
which are cells that are responsible for
maintaining normal peristaltic activity.
They're relatively rare
kind of gastric cancers,
but ones that is necessary
that we specifically identify
because treatment is targeted to unique
mutations that occur in these tumors.
And then finally,
And these are relatively rare.
They're very slow growing.
They're neuroendocrine tumors.
They tend to have a much
more indolent course.
So we've talked
about the other ones.
We talked about MALT lymphomas
and the GISTs and the carcinoid.
We're really going to focus here on
the carcinomas, epithelial malignancy.
Let's talk about
So risk factors for gastric carcinoma
is inflammation of the stomach.
And so anything that will cause
inflammation of the stomach
which causes mucosal damage,
and inflammation which is going to
release a variety of cytokine mediators
and reactive oxygen species is going to
drive the production of epithelial tumors.
So gastroesophageal reflux disease
or GERD is going to be a cause.
Obesity in general is
associated with this
that may actually reflect a
certain amount of reflux disease.
Remember that obesity is
a risk factor for GERD.
so things that are in
the diet can also impact
the development of
Clearly Helicobacter pylori infection and
I've already mentioned about five times,
so it's probably
Gastritis not otherwise specified
any inflammation of the GI lining,
of the stomach lining
will cause increased risk.
Because smoking reduces
the mucus production
which will be an increased
risk for gastritis.
So normally, the bile is released
into the first part of the duodenum,
second part of the duodenum
and goes more distal.
Sometimes that can reflux through
the pylorus into the stomach.
And bile can be an
but can also induce the production
of inflammatory mediators.
And then there are a variety of genetic
underpinnings for gastric malignancy.
So hereditary nonpolyposis,
colorectal cancer, abbreviated HNPCC,
Those specific mutations
associated with those entities
can give you an increased
risk of gastric cancer
as well as epithelial malignancies
elsewhere in the GI tract.
So this is just a
schematic kind of a cartoon
to give you a sense of the
basic mechanism by which injury
in quotation marks not
can ultimately cause malignancy.
So we have injury,
it could be Helicobacter,
it could be smoking,
it could be a whole variety of things
that cause inflammation
An injury will
cause loss of cells.
And to replace those
cells, we make more cells.
So we have
So we have now new
DNA being synthesized.
At the same time that
injury has also elicited
the recruitment of
Those cells are making a variety of
mediators that are part of inflammation,
Reactive oxygen species
will cause mutations
can cause DNA
breaks, for example.
And now we can have DNA breaks occurring
in the setting of proliferating cells.
That's a recipe for
or for the generation of mutations that
get permanently locked into the genome.
So we'll acquire
Oops, now we're on our way to
malignancy and invasive cancers.
So I've talked about
the intestinal type.
I just want to spend a moment
talking about the diffuse type.
a Latin phrase meaning leather bottle.
On the left hand side,
you see an example of a leather bottle.
It used to be the way that the
ancient Romans would transport
their various liquids in
a leather pouch like that.
The thickness and kind of the diffuse
kind of thickening of the wall
is what gives it that
leather bottle appearance.
So this is that
So it's associated
not so much with the typical inflammatory
mediators that we just talked about,
but by specific mutations.
And in particular,
we see loss of function mutations in CDH1,
that's a tumor suppressor gene,
that is encoding the
adhesion protein E-cadherin.
Loss of that leads to
and it tends to give rise to
that diffuse infiltrative tumor.
This is just showing you
example of what this looks like.
So the tumor cells are I
highlighted here with green circles.
They are adenocarcinoma so
they have mucin within them,
and they tend to
be kind of sneaky.
They are infiltrating and
inducing the local tissue
around them to
produce a fibrosis
that's how we get that thick leather
bottle sort of appearance grossly.
So the clinical presentation
of cancers of the stomach.
In the early stages, as you might
expect, it can be asymptomatic.
As we develop symptomatology that usually
suggest much more advanced cancer.
And the main reason it's the third leading
cause of cancer mortality in the world
is that it usually is discovered at a
stage where it's much more advanced.
So the symptoms suggesting worse kind
of prognosis and more advanced disease
include epigastric discomfort
actually feeling like
there is a a mass
or a pain there.
A combination of the tumor and
some of the factors that it makes,
as well as just
pressure at that spot,
the patient may develop anorexia,
doesn't feel like eating,
there may be nausea.
There may be weight loss
as a result of not eating
and not having good flow of food,
nutrition through the stomach
and into the rest
of the GI tract.
As we get further along, there's going
to be increasing levels of nausea.
To the satiety becomes
even earlier and earlier,
very little food will make you
feel like you're completely full.
You may have a formal
and in that case may have
vomiting after ingesting food.
And as the tumor erodes and and
undergoes focal necrosis itself,
you may develop either vomiting of
or you may have Melena,
you may have dark tarry stools
into the GI tract
that eventually comes
out at the distal end.
The signs overall, there may be
a completely normal physical exam
or there may be an
particularly of metastatic disease,
you may have an enlarged liver,
a palpable liver mass
or a very irregular margin
underneath the right upper quadrant
underneath the ribcage.
A Virchow's node is the node
that sits right at the junction
of the thoracic duct and
left subclavian vein.
And it is about right
there, an enlarged node.
There is classic for
For reasons I don't
understand an Irish node
can occur in the left
excellent again drainage
presumably from lymphatics
coming of a gastric cancer.
You can have a Sister Mary Joseph's
nodule which is actually going out
old umbilical vein connections so that
you get a periumbilical nodule of tumor
and the tumor may slough on
the surface of the stomach
and/or may have increased
and then you will
develop in a sideways.
And these are not unique
to gastric carcinoma,
they occur in a
variety of carcinomas.
But you can get a acanthosis
nigricans kind of a soft,
velvety hyper pigmented
This is due to keratinocyte
activation and proliferation.
You can get multiple
a dermatomyositis, so autoimmune
inflammatory disease may happen.
states are very common
particularly with the adenocarcinomas
at a linitis plastica of variety
and a membranous nephropathy usually
due to immune complex deposition.
So in patients
who are high risk,
that is to say patients with
familial adenomatous polyposis,
colorectal cancer and others,
we will constantly surveil and hopefully
pick up malignancy by doing endoscopy,
an earlier stage and
be able to intervene.
Patients who have a prior
history of gastric adenomas,
little benign proliferations of the
gastric epithelium are also at high risk.
If there has been a prolonged
history of gastritis,
whether it's atrophic or not,
that chronic inflammation
hitting the gastric epithelium
is going to put the
patient at increased risk.
And then we've already identified
certain high risk ethnic populations,
Eastern European and South America.
Our main diagnostic modality is going
to be esophagogastroduodenoscopy, EGD.
And we're going to look
for ulcerated masses,
irregular heaped up
margins, and induration.
And in linitis plastica,
it actually may be much more subtle.
Remember, just had those sneaky little
cells kind of going throughout the wall.
But what we'll see is
the wall is very stiff.
So it doesn't really
And we may not see really good rugal
folds, for example in the stomach.
Overall, unless you have a really deep
ulceration associate with the tumor,
barium imaging has
much lower sensitivity
and you really
want to do an EGD.
How are we going to manage this?
Well, I already told you,
the vast majority of patients
are going to present
later in the course.
So, although we can do surgery,
although we can do chemotherapy,
those are not in general going
to give us a very happy outcome.
So, if Helicobacter pylori is a driving
force in this, you can definitely do that.
But at the point you've made
the diagnosis of cancer,
additional Helicobacter pylori therapy
is not going to make a huge difference.
The clinical staging is going to be very
important for dictating our therapies.
So if it's non metastatic,
usually or more commonly,
you will have a successful outcome
with chemotherapy and surgery.
With metastatic disease,
our chemotherapies are usually
not going to be successful.
And you may do a palliative
just to prevent obstruction
or severe bleeding.
But chemotherapy and radiation,
everything else you're going to do is
usually not going to have a good outcome
once we have metastatic spread.
So the overall 5-year
survival is 30%.
I already said this
is a bad actor,
the third leading cause of
cancer mortality in the world.
Even with curative surgical
resection where we got it all,
the patients are about 50/50 in
terms of their 5-year survival.
And the stages that are there.
So local disease,
local disease of a certain size,
local disease with nodal spread
or distant disease stages 1-4,
you can see the survival curves
and overall not a happy outcome.
not super uplifting topic,
but one, especially in large portions of
the world we need to pay attention to.
I hope you've enjoyed the
talk on gastric carcinoma.