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S: This is Sal again, and this is 4th in a series we're doing here at Stanford Med School w/Dr. Connolly.

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Dr: This is the 4th of the slides, and this would now be the reason why this section of colon was removed.

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This is cancer. So, just to orient. We're going to go to drawing.

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Like you said before, this is the lumen, the inside. Out here is the rest of your belly.

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S: Is there a word for your abdominal [insides]?

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Dr: Peritoneal. So the peritoneal cavity is where all the bowel loops are just moving around.

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What we have here is an important part, this is the muscle that allows peristalsis.

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S: The undulating motion to push stuff.

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Dr: Yes. It will milk it along. So the muscle is all fine there, that's how thick it's supposed to be,

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and it's all fine here...

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S: What scale is this? How thick is that muscle?

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Dr: Our tiny little red blood cells are those tiny dots there, and so we're talking thickness here of

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about a few millimeters.

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S: So that muscle is a few millimeters.

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Dr: Right. So remember that guy was about 6mm? That's about 6mm.

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Dr: That's actually strong, a very strong muscle, you can kinda see it go up here,

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it comes around here, but it looks like it's trouble along this area.

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S: And this stuff was probably once a polyp and it just turned into this massive polyp?

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Dr: Yes. So, we have the normal here, for the lining, this is where it's going dysplastic.

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There's where it's going dysplastic.

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And so now what happens is you got these edges of dysplasia..

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S: When people in the medical field say "plastic," they word means...tissue?

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Dr: Plastic in general, like plastic surgery, or the plastics in material science,

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means moldable. It also means you can grow, you can change shape.

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S: So when you call something plastic, it's moldable tissue?

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Dr: It's the shape changes. So the shape changes were wrong.

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Actually, dysplasia can refer to a cell, tissue, an organ, or an entire limb.

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It just means that it grew wrong, it molded wrong.

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So now, this is where we have the cell dysplasia,

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this is all the bad stuff. It basically started somewhere up there and started invading.

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S: Just one cell up there started dividing uncontrollably.

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Dr: Right. It could have started from one cell being very bad,

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it often starts though from one of these, meaning maybe a cell went bad right around there,

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Now it's really starting to grow.

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S: When you say grow, not the one cell but all of its descendants?

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Dr: Its descendants. Millions and billions are now growing downward to now, in this case,

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grow all the way through. And so you can see the scale is it not only grew a little bit,

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it went right through the muscle.

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S: The body does have some things to fight this off? But it was unsuccessful?

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Dr: Right. There are certain conditions where if you decrease the immune functions

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you'll get cancer. It's still argued if when the immune system decreases you get a virus,

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and a virus causes the cancer, or whether the immune system is [actively watching out for cancer].

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S: The whole notion of viruses is fascinating, because a lot of our ancient DNA is from viruses...

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Dr: Yeah. There are some categories, where viruses can get into your DNA and really mess up your DNA,

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and integrate into it, but viruses can also lead to irritation, with more cell growth and [likelihood

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for DNA copy errors].

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So now we're back where we're looking at the cancer that probably started around here,

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and is growing, including spreading all the normal tissue around it.

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Now we're going to look at the cells.

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First, look at the edges of this. We find normal, though not perfectly normal.

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You can see it's a little bit dividing and a little bit irritated. This is irritated along the edge.

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S: Hyperplasia.

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Dr: Exactly! What we have when we go deeper, this is all coming out, growing in all directions,

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this is where you can see cancer next to the normal.

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We talked before about dysplasia, but this right here is really bad.

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These are the normal ones, they're doing their job. They're making mucin, nuclei at the bottom,

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What is this guy doing? It's just chaos. Before we talked about carcinoma in situ,

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a cancer in a spot--if you saw cells this bad, you'd say, do not let them go far.

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Because they will have a tendency to invade. They're crazy. So this right here is a bunch of the cells,

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this is a bunch of the cells, they're these guys here.

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You can see they're really haphazard in how they're growing,

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they're not doing their job...

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S: If we had a polyp that had this stuff that hadn't crossed that boundary line yet,

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we'd still say, "We got to take this out."

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...although I guess we already took it out.

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Dr: Cancer of the colon is one of the ones where surgical cures still applies.

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Cut it out, and you are probably in pretty good shape.

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So if it looked like this only at the tip of the polyp, we'd probably got it out,

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But you'd say to yourself, "We better watch this person."

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S: If the whole polyp looked like that, you'd cut out a bigger section?

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Dr: Yes, if it's going down into the neck, or going a little further,

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or if you had cut it across the margin, then watch out.

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But here's the problem: Remember how I said up here it's not a big deal?

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But once you get near the veins and arteries?

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These guys are running amuck, near the veins and arteries,

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S: You can see these cells have split off, and infiltrating...

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Dr: That's one little nest of cells,

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that one is probably a cancer cell just dying to get into that little vein.

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S: So this is metastasis?

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Dr: This is where it would come from. So these guys are the bad actors,

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growing next to these very fragile blood vessels, so that guy is knocking on the door,

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wants to get in here--that's a venule, a little vein, that's the road out.

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S: It looks like a circle here because it's a 2D cross-section of it,

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but you can imagine it popping in and out of our screen.

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Dr: Yes. So this guy might pop in and out of screen, connect to this one...

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S: And it officially metastasized once it's found a beachhead someplace else?

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Dr: Right. It's considered a metastasis if the cell got into the vessel and left the region,

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This is looking like you really are worrying that this could metastasize.

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What's interesting is when you're looking at something like this, there's something called

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pre-cancer grade, and what grade is is what we've been talking about--

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how bad does that look? And so the grade is, "Wow, that looks nasty."

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S: Is nasty a technical term?

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Dr: Actually we use it quite a bit. When we talk about nastiness, it's a lack of behavour,

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if you can get a cell where the nucleus gets that big, or sometimes that big,

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there's chaos. And there's chaos not just in the nuclear size, but how it behaves.

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S: The nuclear size indicates that the cell is devoting cell replication?

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Dr: Yes. But it also means to me--normally things in the cell are very orderly,

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you do not divide your DNA until these things--now it's just left and right.

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This would be a high-grade tumor, and stage is the other main thing.

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Stage means where is it in the body.

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So in this case, if these nasty cells were only at the very top, it would be a lower stage than

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these which have come all the way down here.

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S: In situ carcinoma, what is the stage?

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Dr: Stage 0. It's basically nowhere. If you just begin to crossover, it's stage 1;

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and then there's depth for some stages, and then there's always "did it go to other parts of your body?"

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And that's the very highest stage

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S: And this is true of all cancer--when someone speaks of breast cancer, I've heard of stage 0-4,

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It isn't just the size--if the cancerous tissue is big, but in a safe place, still be stage 1 or 2?

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Dr: It is. The whole world has agreed to the same kind of staging, and that staging is what we're calling TNM.

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T has to do with how big it is, and how much it's crossed any barriers,

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N has to do with if they are in lymph nodes. The lymph nodes are nearby structures where the lymph goes.

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M has to do with metastasis.

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Staging has to do with all three.

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S: Metastases always has to happen through the circulatory system?

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Through the blood vessels, or does it also happen through the lymph network?

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Dr: It's something where going through the lymph nodes is one of the first steps for something like this,

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but getting to the liver or the lung, it's got to get into the blood vessels.

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The lymphatic in your colon connects to a local lymph node,

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but does not connect through lymph only to the (...? be quieter, Sal!)

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So it must have gone through the blood somewhere.

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So that's the way it looks here. And the final thing when looking at this cancer is

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if we go over here, this is the greatest depth of invasion.

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You had asked me about the body's immune function.

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Well, if you look here, you see how it's kind of loose?

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There is all these little immune cells?

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S: What's the immune cells?

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Dr: These guys here. These little round guys? These are lymphocytes.

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S: How can you tell the difference between the lymphocytes and the cancer cells?

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Dr: Because I'm a pathologist...

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They're these little round ones. Right here is a classic cell, which is called a plasma cell

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in which there is a nucleus here, and all the rest is making antibodies

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S: You're not circling that area are you?

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Dr: No, I'm just drawing. So this guy is this one. So I'm zooming in on him.

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Dr: That's a plasma cell, that's making antibodies probably against the tumor.

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That's the immune response in that spot.

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S: How do you know...that looks very similar to the cancer cells?

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Dr: This one is a little hard to tell. If you had a real microscope, you'd turn up the light,

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this would have a very specific look to the nucleus,

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and these guys over here have little pink granules in them,

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which is a type of immune cell.

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S: Which ones are cancerous here?

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Dr: These are all inflammation. The nearest cancer cells are these guys up here.

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S: On this view it becomes obvious, they look different.

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Dr: When you come out here, there's the cancer,

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there's the body's reaction to the cancer.

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There are therapies based on trying to get more of this immune response.

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S: Very cool 8-)