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Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:10.06,0:00:15.64,Default,,0000,0000,0000,,(From M1 Patients and Populations at University of Michigan Medical School. Lecture by Gerald Abrams, MD.)\NI think a good place to start is with\Nthis slide again, just to remind you that
Dialogue: 0,0:00:15.64,0:00:16.08,Default,,0000,0000,0000,,one of the defining
Dialogue: 0,0:00:16.08,0:00:19.75,Default,,0000,0000,0000,,traits of malignant
Dialogue: 0,0:00:19.75,0:00:25.04,Default,,0000,0000,0000,,neoplasms is the ability to invade
Dialogue: 0,0:00:25.04,0:00:27.29,Default,,0000,0000,0000,,more importantly even
Dialogue: 0,0:00:27.29,0:00:29.01,Default,,0000,0000,0000,,as
Dialogue: 0,0:00:29.01,0:00:34.09,Default,,0000,0000,0000,,a second defining characteristic is\Nthe ability to set up
Dialogue: 0,0:00:34.09,0:00:37.01,Default,,0000,0000,0000,,underlying distant
Dialogue: 0,0:00:37.01,0:00:38.06,Default,,0000,0000,0000,,and
Dialogue: 0,0:00:38.06,0:00:39.10,Default,,0000,0000,0000,,discontinuous
Dialogue: 0,0:00:39.10,0:00:45.00,Default,,0000,0000,0000,,secondary foci of growth. What this involves is cells
Dialogue: 0,0:00:45.00,0:00:49.06,Default,,0000,0000,0000,,breaking off, leaving, what we\Ncall, the primary cells
Dialogue: 0,0:00:49.06,0:00:51.02,Default,,0000,0000,0000,,getting
Dialogue: 0,0:00:51.02,0:00:55.08,Default,,0000,0000,0000,,into the moving currents or fluids that\Nflow into the body, let's say into the blood
Dialogue: 0,0:00:55.08,0:00:57.09,Default,,0000,0000,0000,,or into the lymph
Dialogue: 0,0:00:57.09,0:00:58.58,Default,,0000,0000,0000,,lodging at a
Dialogue: 0,0:00:58.58,0:01:01.06,Default,,0000,0000,0000,,distance, in other words, here is the\Nprimary
Dialogue: 0,0:01:01.06,0:01:03.09,Default,,0000,0000,0000,,clump of cells, these cells
Dialogue: 0,0:01:03.09,0:01:06.04,Default,,0000,0000,0000,,float over there, they lodge and
Dialogue: 0,0:01:06.04,0:01:08.61,Default,,0000,0000,0000,,get out of the vessel they are in
Dialogue: 0,0:01:08.61,0:01:11.04,Default,,0000,0000,0000,,and they form a new nodule.
Dialogue: 0,0:01:11.04,0:01:13.01,Default,,0000,0000,0000,,That's the process of metastasis.
Dialogue: 0,0:01:13.01,0:01:18.05,Default,,0000,0000,0000,,That's what the process is called. The focus itself is called him a metastasis (or plural metastases).
Dialogue: 0,0:01:18.05,0:01:18.100,Default,,0000,0000,0000,,
Dialogue: 0,0:01:18.100,0:01:21.08,Default,,0000,0000,0000,,and the
Dialogue: 0,0:01:21.08,0:01:24.06,Default,,0000,0000,0000,,ability to metastasize
Dialogue: 0,0:01:24.06,0:01:27.01,Default,,0000,0000,0000,,by all odds is the most lethal aspect of cancer.
Dialogue: 0,0:01:27.01,0:01:29.08,Default,,0000,0000,0000,,And
Dialogue: 0,0:01:29.08,0:01:33.02,Default,,0000,0000,0000,,that's the the feature that most often
Dialogue: 0,0:01:33.02,0:01:35.05,Default,,0000,0000,0000,,makes a cancer incurable.
Dialogue: 0,0:01:35.05,0:01:39.07,Default,,0000,0000,0000,,Sometimes a cancer is incurable\Nbecause of local invasion, you know,
Dialogue: 0,0:01:39.07,0:01:45.00,Default,,0000,0000,0000,,something wraps around the aorta or some other structure, you can't get at it,
Dialogue: 0,0:01:45.00,0:01:45.58,Default,,0000,0000,0000,,that could be
Dialogue: 0,0:01:45.58,0:01:51.06,Default,,0000,0000,0000,,lethal but it's usually metastasis. The sad fact is that
Dialogue: 0,0:01:51.06,0:01:55.02,Default,,0000,0000,0000,,if you exclude skin cancers, many of which are in a different category, if you exclude those
Dialogue: 0,0:01:55.02,0:01:57.01,Default,,0000,0000,0000,,about
Dialogue: 0,0:01:57.01,0:02:01.08,Default,,0000,0000,0000,,thirty to fifty percent of\Npatients who present to their doctors
Dialogue: 0,0:02:01.08,0:02:05.02,Default,,0000,0000,0000,,with some signs and symptoms that turn out to be cancer, about thirty to
Dialogue: 0,0:02:05.02,0:02:08.83,Default,,0000,0000,0000,,fifty percent already have metastases.
Dialogue: 0,0:02:08.83,0:02:11.52,Default,,0000,0000,0000,,So it's something that really
Dialogue: 0,0:02:11.52,0:02:13.03,Default,,0000,0000,0000,,is the biggest roadblock
Dialogue: 0,0:02:13.03,0:02:13.71,Default,,0000,0000,0000,,
Dialogue: 0,0:02:13.71,0:02:16.82,Default,,0000,0000,0000,,to successful treatment.
Dialogue: 0,0:02:16.82,0:02:20.66,Default,,0000,0000,0000,,So again these defining characteristics
Dialogue: 0,0:02:20.66,0:02:25.50,Default,,0000,0000,0000,,are invasion and metastasis. Now
Dialogue: 0,0:02:25.50,0:02:28.06,Default,,0000,0000,0000,,these abilities, to talk first about invasion and metastasis together,
Dialogue: 0,0:02:28.06,0:02:30.08,Default,,0000,0000,0000,,
Dialogue: 0,0:02:30.08,0:02:34.46,Default,,0000,0000,0000,,are not just a matter of cell proliferation
Dialogue: 0,0:02:34.46,0:02:36.06,Default,,0000,0000,0000,,in other words, it's not the matter of fact
Dialogue: 0,0:02:36.06,0:02:40.00,Default,,0000,0000,0000,,that the cancers proliferating in the\Nprimary so much that the cells get squeezed
Dialogue: 0,0:02:40.00,0:02:42.03,Default,,0000,0000,0000,,out and they move. That's nonsense.
Dialogue: 0,0:02:42.03,0:02:44.63,Default,,0000,0000,0000,,Some primaries grow very large and then
Dialogue: 0,0:02:44.63,0:02:46.60,Default,,0000,0000,0000,,never leave
Dialogue: 0,0:02:46.60,0:02:52.62,Default,,0000,0000,0000,,the local area. These neoplasms acquire
Dialogue: 0,0:02:52.62,0:02:53.04,Default,,0000,0000,0000,,the
Dialogue: 0,0:02:53.04,0:02:58.02,Default,,0000,0000,0000,,cells in the neoplasm gradually acquire the ability to invade
Dialogue: 0,0:02:58.02,0:03:02.19,Default,,0000,0000,0000,,and to metastasize, and again these\Nrepresent an accumulation
Dialogue: 0,0:03:02.19,0:03:05.78,Default,,0000,0000,0000,,of different kinds of mutations very likely giving the cells the
Dialogue: 0,0:03:05.78,0:03:06.08,Default,,0000,0000,0000,,the ability to
Dialogue: 0,0:03:06.08,0:03:08.37,Default,,0000,0000,0000,,do this.
Dialogue: 0,0:03:08.37,0:03:10.06,Default,,0000,0000,0000,,Now metastasis I would emphasize
Dialogue: 0,0:03:10.06,0:03:13.00,Default,,0000,0000,0000,,is a very complex cascade of events,
Dialogue: 0,0:03:13.00,0:03:14.09,Default,,0000,0000,0000,,
Dialogue: 0,0:03:14.09,0:03:16.53,Default,,0000,0000,0000,,it's not just whoops!
Dialogue: 0,0:03:16.53,0:03:17.06,Default,,0000,0000,0000,,but involves the
Dialogue: 0,0:03:17.06,0:03:21.08,Default,,0000,0000,0000,,cells first of all invading, getting through that extracellular matrix,
Dialogue: 0,0:03:21.08,0:03:23.78,Default,,0000,0000,0000,,breaking through basement membrane,
Dialogue: 0,0:03:23.78,0:03:28.60,Default,,0000,0000,0000,,getting into a vessel whether it's a\Nblood vessel or a lymphatic, floating
Dialogue: 0,0:03:28.60,0:03:32.75,Default,,0000,0000,0000,,with the stream and surviving\Nduring that flotation, which is another
Dialogue: 0,0:03:32.75,0:03:34.32,Default,,0000,0000,0000,,nice trick, lodging
Dialogue: 0,0:03:34.32,0:03:35.10,Default,,0000,0000,0000,,somewhere,
Dialogue: 0,0:03:35.10,0:03:40.28,Default,,0000,0000,0000,,being able to extravasate, get out of that\Nvessel where it lodged,
Dialogue: 0,0:03:40.28,0:03:45.29,Default,,0000,0000,0000,,and set up housekeeping and get all of\Nthe requirements for growing another nodule.
Dialogue: 0,0:03:45.29,0:03:49.19,Default,,0000,0000,0000,,this is sort of, its been\Nlikened to, a decathlon event. You have to
Dialogue: 0,0:03:49.19,0:03:49.05,Default,,0000,0000,0000,,win
Dialogue: 0,0:03:49.05,0:03:52.19,Default,,0000,0000,0000,,a lot of events to be a successful metastasis.
Dialogue: 0,0:03:52.19,0:03:54.73,Default,,0000,0000,0000,,and
Dialogue: 0,0:03:54.73,0:03:58.30,Default,,0000,0000,0000,,there are three primary roots, this one is the lesser but
Dialogue: 0,0:03:58.30,0:03:59.04,Default,,0000,0000,0000,,cells
Dialogue: 0,0:03:59.04,0:04:04.02,Default,,0000,0000,0000,,can metastasize via the bloodstream, via the lymph flow
Dialogue: 0,0:04:04.02,0:04:05.09,Default,,0000,0000,0000,,and sometimes directly.
Dialogue: 0,0:04:05.09,0:04:08.12,Default,,0000,0000,0000,,Now here
Dialogue: 0,0:04:08.12,0:04:11.32,Default,,0000,0000,0000,,for instance, just to illustrate this,
Dialogue: 0,0:04:11.32,0:04:13.90,Default,,0000,0000,0000,,here is a clump of cancer cells within a
Dialogue: 0,0:04:13.90,0:04:16.01,Default,,0000,0000,0000,,tiny vein
Dialogue: 0,0:04:16.01,0:04:18.27,Default,,0000,0000,0000,,within adipose tissue.
Dialogue: 0,0:04:18.27,0:04:19.07,Default,,0000,0000,0000,,This was actually
Dialogue: 0,0:04:19.07,0:04:24.01,Default,,0000,0000,0000,,in a breast that had been removed by mastectomy, this was, in other words,
Dialogue: 0,0:04:24.01,0:04:26.26,Default,,0000,0000,0000,,primary cancer of the breast.
Dialogue: 0,0:04:26.26,0:04:27.08,Default,,0000,0000,0000,,What had happened here
Dialogue: 0,0:04:27.08,0:04:29.82,Default,,0000,0000,0000,,a tongue of cells had
Dialogue: 0,0:04:29.82,0:04:34.03,Default,,0000,0000,0000,,broken through a venule wall somewhere upstream
Dialogue: 0,0:04:34.03,0:04:36.09,Default,,0000,0000,0000,,and here you see it caught in the act of floating
Dialogue: 0,0:04:36.09,0:04:38.90,Default,,0000,0000,0000,,with the blood.
Dialogue: 0,0:04:38.90,0:04:43.75,Default,,0000,0000,0000,,Now there's a certain predictability to where the metastasis will go. In this case,
Dialogue: 0,0:04:43.75,0:04:47.13,Default,,0000,0000,0000,,this is coming from the breast. Eventually
Dialogue: 0,0:04:47.13,0:04:50.63,Default,,0000,0000,0000,,these venules are going to go into veins which are going to flow into
Dialogue: 0,0:04:50.63,0:04:52.70,Default,,0000,0000,0000,,the superior vena cava. The cells
Dialogue: 0,0:04:52.70,0:04:55.07,Default,,0000,0000,0000,,aren't going to lodge anywhere along there because the vessels are getting bigger
Dialogue: 0,0:04:55.07,0:04:57.07,Default,,0000,0000,0000,,and bigger. And
Dialogue: 0,0:04:57.07,0:04:58.15,Default,,0000,0000,0000,,they
Dialogue: 0,0:04:58.15,0:05:01.08,Default,,0000,0000,0000,,go to the right side of the heart out the pulmonary artery.
Dialogue: 0,0:05:01.08,0:05:02.10,Default,,0000,0000,0000,,Pretty soon, these cells
Dialogue: 0,0:05:02.10,0:05:08.38,Default,,0000,0000,0000,,are going to encounter the capillaries in the lungs where they are going to lodge.
Dialogue: 0,0:05:08.38,0:05:09.00,Default,,0000,0000,0000,,Metastasis,
Dialogue: 0,0:05:09.00,0:05:13.69,Default,,0000,0000,0000,,a cell clump like this, if it's successful, may
Dialogue: 0,0:05:13.69,0:05:14.08,Default,,0000,0000,0000,,very well
Dialogue: 0,0:05:14.08,0:05:17.20,Default,,0000,0000,0000,,end up in the lungs.
Dialogue: 0,0:05:17.20,0:05:21.26,Default,,0000,0000,0000,,Now you haven't studied this in gross anatomy yet, you're just beginning gross,
Dialogue: 0,0:05:21.26,0:05:22.04,Default,,0000,0000,0000,,but
Dialogue: 0,0:05:22.04,0:05:24.03,Default,,0000,0000,0000,,I'll tell you that for instance
Dialogue: 0,0:05:24.03,0:05:29.04,Default,,0000,0000,0000,,the blood flow drainage, the venous drainage of the GI tract
Dialogue: 0,0:05:29.04,0:05:31.57,Default,,0000,0000,0000,,goes into what we call the portal vein, which is
Dialogue: 0,0:05:31.57,0:05:33.19,Default,,0000,0000,0000,,a big vein
Dialogue: 0,0:05:33.19,0:05:35.13,Default,,0000,0000,0000,,that goes into the liver.
Dialogue: 0,0:05:35.13,0:05:40.05,Default,,0000,0000,0000,,Now the cells, if these cells had broken out of a gastric cancer,
Dialogue: 0,0:05:40.05,0:05:41.03,Default,,0000,0000,0000,,and
Dialogue: 0,0:05:41.03,0:05:43.09,Default,,0000,0000,0000,,were in the veins draining the stomach, they would
Dialogue: 0,0:05:43.09,0:05:47.00,Default,,0000,0000,0000,,go into this portal vein and then the first capillary bed
Dialogue: 0,0:05:47.00,0:05:48.04,Default,,0000,0000,0000,,they hit is the liver.
Dialogue: 0,0:05:48.04,0:05:50.00,Default,,0000,0000,0000,,So you'd
Dialogue: 0,0:05:50.00,0:05:55.54,Default,,0000,0000,0000,,find metastases in the liver, you'd predict metastases in the liver.
Dialogue: 0,0:05:55.54,0:05:58.05,Default,,0000,0000,0000,,Or if you had a malignancy in the soft tissues\Nof the leg,
Dialogue: 0,0:05:58.05,0:06:02.01,Default,,0000,0000,0000,,the cells would eventually get to the inferior vena cava, up to the heart,
Dialogue: 0,0:06:02.01,0:06:04.44,Default,,0000,0000,0000,,and into the lungs.
Dialogue: 0,0:06:04.44,0:06:06.76,Default,,0000,0000,0000,,So it turns out that the lungs
Dialogue: 0,0:06:06.76,0:06:10.41,Default,,0000,0000,0000,,and the liver constitute the two big filters in the body
Dialogue: 0,0:06:10.41,0:06:14.01,Default,,0000,0000,0000,,and they catch a lot of metastases.
Dialogue: 0,0:06:14.01,0:06:15.67,Default,,0000,0000,0000,,Now this is nowhere
Dialogue: 0,0:06:15.67,0:06:18.04,Default,,0000,0000,0000,,near being entirely predictable for the
Dialogue: 0,0:06:18.04,0:06:20.09,Default,,0000,0000,0000,,following reasons,
Dialogue: 0,0:06:20.09,0:06:23.10,Default,,0000,0000,0000,,the cancer cells don't necessarily lodge
Dialogue: 0,0:06:23.10,0:06:24.98,Default,,0000,0000,0000,,permanently
Dialogue: 0,0:06:24.98,0:06:28.24,Default,,0000,0000,0000,,in the lungs or the liver.
Dialogue: 0,0:06:28.24,0:06:32.59,Default,,0000,0000,0000,,they change their shape, they squiggle around,
Dialogue: 0,0:06:32.59,0:06:35.73,Default,,0000,0000,0000,,let's say coming from the GI tract, they may get\Nthrough the liver
Dialogue: 0,0:06:35.73,0:06:36.00,Default,,0000,0000,0000,,into the
Dialogue: 0,0:06:36.00,0:06:38.03,Default,,0000,0000,0000,,inferior vena cava up to the
Dialogue: 0,0:06:38.03,0:06:41.15,Default,,0000,0000,0000,,heart and out anywhere in the body.
Dialogue: 0,0:06:41.15,0:06:43.70,Default,,0000,0000,0000,,So it turns out that really practically
Dialogue: 0,0:06:43.70,0:06:47.25,Default,,0000,0000,0000,,speaking, cancer cells once again in circulation are all
Dialogue: 0,0:06:47.25,0:06:49.07,Default,,0000,0000,0000,,over the place
Dialogue: 0,0:06:49.07,0:06:50.38,Default,,0000,0000,0000,,and
Dialogue: 0,0:06:50.38,0:06:53.03,Default,,0000,0000,0000,,it also turns out that there are secondary factors
Dialogue: 0,0:06:53.03,0:06:56.50,Default,,0000,0000,0000,,that determine where the metastases will occur
Dialogue: 0,0:06:56.50,0:06:58.34,Default,,0000,0000,0000,,For instance,
Dialogue: 0,0:06:58.34,0:07:01.84,Default,,0000,0000,0000,,we know that cancer cells get out\Nsystemically. We rarely see metastases
Dialogue: 0,0:07:01.84,0:07:04.03,Default,,0000,0000,0000,,in skeletal muscle. I have no idea
Dialogue: 0,0:07:04.03,0:07:05.64,Default,,0000,0000,0000,,why.
Dialogue: 0,0:07:05.64,0:07:07.06,Default,,0000,0000,0000,,But we rarely do.
Dialogue: 0,0:07:07.06,0:07:11.04,Default,,0000,0000,0000,,It turns out that certain cancers have a propensity
Dialogue: 0,0:07:11.04,0:07:13.90,Default,,0000,0000,0000,,to set up metastases in one
Dialogue: 0,0:07:13.90,0:07:16.04,Default,,0000,0000,0000,,set of tissues and certain cancers
Dialogue: 0,0:07:16.04,0:07:20.01,Default,,0000,0000,0000,,have a propensity to set up metastases in another set of tissues. It's as if they
Dialogue: 0,0:07:20.01,0:07:22.96,Default,,0000,0000,0000,,favor the "taste"
Dialogue: 0,0:07:22.96,0:07:23.06,Default,,0000,0000,0000,,of
Dialogue: 0,0:07:23.06,0:07:24.57,Default,,0000,0000,0000,,one tissue
Dialogue: 0,0:07:24.57,0:07:28.01,Default,,0000,0000,0000,,over another, and you'll learn these patterns, I'm not going to afflict you with them.
Dialogue: 0,0:07:28.01,0:07:30.67,Default,,0000,0000,0000,,They are
Dialogue: 0,0:07:30.67,0:07:34.80,Default,,0000,0000,0000,,to an extent predictable.
Dialogue: 0,0:07:34.80,0:07:39.79,Default,,0000,0000,0000,,So that's the situation with hematogenous metastases, liver, lung,
Dialogue: 0,0:07:39.79,0:07:44.22,Default,,0000,0000,0000,,many other places as well. It's a systemic process
Dialogue: 0,0:07:44.22,0:07:46.47,Default,,0000,0000,0000,,Here are cancer cells in a lymphatic.
Dialogue: 0,0:07:46.47,0:07:50.01,Default,,0000,0000,0000,,You probably know less about lymphatic\Nchannels than you do about blood channels but these are
Dialogue: 0,0:07:50.01,0:07:51.45,Default,,0000,0000,0000,,basically
Dialogue: 0,0:07:51.45,0:07:52.64,Default,,0000,0000,0000,,they start from small, thin walled
Dialogue: 0,0:07:52.64,0:07:54.06,Default,,0000,0000,0000,,vessels like this and
Dialogue: 0,0:07:54.06,0:07:57.40,Default,,0000,0000,0000,,and any particular organ
Dialogue: 0,0:07:57.40,0:08:00.08,Default,,0000,0000,0000,,almost all organs in the body have a rich lymphatic drainage. The lymph
Dialogue: 0,0:08:00.08,0:08:01.43,Default,,0000,0000,0000,,is drained
Dialogue: 0,0:08:01.43,0:08:02.88,Default,,0000,0000,0000,,into bigger
Dialogue: 0,0:08:02.88,0:08:07.10,Default,,0000,0000,0000,,bigger lymphatics. These enter what we call regional lymph nodes.
Dialogue: 0,0:08:07.10,0:08:11.88,Default,,0000,0000,0000,,which we'll study in detail, but these are\Nbasically like little filter beans
Dialogue: 0,0:08:11.88,0:08:13.03,Default,,0000,0000,0000,,and
Dialogue: 0,0:08:13.03,0:08:15.31,Default,,0000,0000,0000,,a clump of
Dialogue: 0,0:08:15.31,0:08:20.42,Default,,0000,0000,0000,,cells like that may well lodge in a regional lymph node.
Dialogue: 0,0:08:20.42,0:08:21.01,Default,,0000,0000,0000,,Now
Dialogue: 0,0:08:21.01,0:08:23.03,Default,,0000,0000,0000,,what denotes a regional lymph node?
Dialogue: 0,0:08:23.03,0:08:25.14,Default,,0000,0000,0000,,In the case of the bowel,
Dialogue: 0,0:08:25.14,0:08:29.37,Default,,0000,0000,0000,,the regional lymph nodes are in the mesentery. In the case of the
Dialogue: 0,0:08:29.37,0:08:30.69,Default,,0000,0000,0000,,breast, the regional
Dialogue: 0,0:08:30.69,0:08:34.25,Default,,0000,0000,0000,,lymph nodes are in the armpit, that's where the lymph is draining.
Dialogue: 0,0:08:34.25,0:08:34.10,Default,,0000,0000,0000,,In the
Dialogue: 0,0:08:34.10,0:08:39.08,Default,,0000,0000,0000,,case of the mouth and throat, the regional lymph nodes are here in the neck.
Dialogue: 0,0:08:39.08,0:08:41.00,Default,,0000,0000,0000,,And there's
Dialogue: 0,0:08:41.00,0:08:43.07,Default,,0000,0000,0000,,a certain predictability
Dialogue: 0,0:08:43.07,0:08:46.08,Default,,0000,0000,0000,,so that if you have a big cancer in the\Nmouth, you're going to
Dialogue: 0,0:08:46.08,0:08:50.00,Default,,0000,0000,0000,,worry about the cervical lymph nodes or the
Dialogue: 0,0:08:50.00,0:08:53.07,Default,,0000,0000,0000,,or the breast you're going to worry about what's going on in the axilla.
Dialogue: 0,0:08:53.07,0:08:57.00,Default,,0000,0000,0000,,Cancer operations generally involve
Dialogue: 0,0:08:57.00,0:09:01.06,Default,,0000,0000,0000,,either excavation or sampling of the\Nregional lymph nodes to see whether the cancer
Dialogue: 0,0:09:01.06,0:09:04.02,Default,,0000,0000,0000,,has spread from the primary there.
Dialogue: 0,0:09:04.02,0:09:06.04,Default,,0000,0000,0000,,Now
Dialogue: 0,0:09:06.04,0:09:10.00,Default,,0000,0000,0000,,this predictability again can break down because
Dialogue: 0,0:09:10.00,0:09:13.02,Default,,0000,0000,0000,,lymph nodes are not perfect filters,
Dialogue: 0,0:09:13.02,0:09:15.04,Default,,0000,0000,0000,,whatever you might think,
Dialogue: 0,0:09:15.04,0:09:19.00,Default,,0000,0000,0000,,these cells might lodge temporarily in a lymph node and some of their progeny
Dialogue: 0,0:09:19.00,0:09:22.00,Default,,0000,0000,0000,,maybe goes scooting out the other side in the
Dialogue: 0,0:09:22.00,0:09:23.01,Default,,0000,0000,0000,,efferent lymph which
Dialogue: 0,0:09:23.01,0:09:27.34,Default,,0000,0000,0000,,is going to go to other lymphatic channels and eventually dump into the
Dialogue: 0,0:09:27.34,0:09:29.05,Default,,0000,0000,0000,,superior vena cava and
Dialogue: 0,0:09:29.05,0:09:31.08,Default,,0000,0000,0000,,join
Dialogue: 0,0:09:31.08,0:09:33.05,Default,,0000,0000,0000,,the systemic circulation.
Dialogue: 0,0:09:33.05,0:09:35.08,Default,,0000,0000,0000,,So it turns out that cancer,
Dialogue: 0,0:09:35.08,0:09:44.04,Default,,0000,0000,0000,,we have to conceive of it is a\Npotentially systemic disease,
Dialogue: 0,0:09:44.04,0:09:46.06,Default,,0000,0000,0000,,One comment
Dialogue: 0,0:09:46.06,0:09:50.06,Default,,0000,0000,0000,,here about metastasis is the possibility of direct metastasis.
Dialogue: 0,0:09:50.06,0:09:51.06,Default,,0000,0000,0000,,By that I mean
Dialogue: 0,0:09:51.06,0:09:53.89,Default,,0000,0000,0000,,the cells are not picked up in the blood or lymph, but
Dialogue: 0,0:09:53.89,0:09:55.06,Default,,0000,0000,0000,,if they enter
Dialogue: 0,0:09:55.06,0:09:59.01,Default,,0000,0000,0000,,a cavity, let's say the peritoneal cavity,
Dialogue: 0,0:09:59.01,0:10:01.06,Default,,0000,0000,0000,,and can drift
Dialogue: 0,0:10:01.06,0:10:03.05,Default,,0000,0000,0000,,or swim or float
Dialogue: 0,0:10:03.05,0:10:05.08,Default,,0000,0000,0000,,across the peritoneal cavity and lodge
Dialogue: 0,0:10:05.08,0:10:06.08,Default,,0000,0000,0000,,anywhere in the lining
Dialogue: 0,0:10:06.08,0:10:09.08,Default,,0000,0000,0000,,of the peritoneal cavity, it's a sort of direct
Dialogue: 0,0:10:09.08,0:10:11.03,Default,,0000,0000,0000,,metastasis.
Dialogue: 0,0:10:11.03,0:10:13.02,Default,,0000,0000,0000,,We see this
Dialogue: 0,0:10:13.02,0:10:14.06,Default,,0000,0000,0000,,one
Dialogue: 0,0:10:14.06,0:10:16.44,Default,,0000,0000,0000,,that comes to mind is the ovary.
Dialogue: 0,0:10:16.44,0:10:19.00,Default,,0000,0000,0000,,The ovary sit out in the pelvis,
Dialogue: 0,0:10:19.00,0:10:24.00,Default,,0000,0000,0000,,in the open so to speak, in the peritoneal cavity. Ovarian cancers notoriously
Dialogue: 0,0:10:24.00,0:10:28.03,Default,,0000,0000,0000,,will just seed cells into the peritoneum and they'll land
Dialogue: 0,0:10:28.03,0:10:28.09,Default,,0000,0000,0000,,anywhere in the peritoneum
Dialogue: 0,0:10:28.09,0:10:29.09,Default,,0000,0000,0000,,and set up these metastases.
Dialogue: 0,0:10:29.09,0:10:32.07,Default,,0000,0000,0000,,A variation on
Dialogue: 0,0:10:32.07,0:10:36.05,Default,,0000,0000,0000,,this that we don't often see is that the surgeon's knife
Dialogue: 0,0:10:36.05,0:10:37.08,Default,,0000,0000,0000,,may pick up
Dialogue: 0,0:10:37.08,0:10:40.02,Default,,0000,0000,0000,,some cancer cells and
Dialogue: 0,0:10:40.02,0:10:44.08,Default,,0000,0000,0000,,we'll find a recurrence in the incision or something of that sort.
Dialogue: 0,0:10:44.08,0:10:46.09,Default,,0000,0000,0000,,More or less
Dialogue: 0,0:10:46.09,0:10:49.06,Default,,0000,0000,0000,,a direct, iatrogenic (physician caused) metastasis.
Dialogue: 0,0:10:49.06,0:10:51.00,Default,,0000,0000,0000,,But again
Dialogue: 0,0:10:51.00,0:10:52.08,Default,,0000,0000,0000,,metastases
Dialogue: 0,0:10:52.08,0:10:57.04,Default,,0000,0000,0000,,represent a hop skip and jump, it's not direct invasion to
Dialogue: 0,0:10:57.04,0:10:59.06,Default,,0000,0000,0000,,get over here, it's a jump
Dialogue: 0,0:10:59.06,0:11:04.09,Default,,0000,0000,0000,,to get over there.
Dialogue: 0,0:11:04.09,0:11:07.07,Default,,0000,0000,0000,,A thing to point out is that the
Dialogue: 0,0:11:07.07,0:11:11.05,Default,,0000,0000,0000,,metastasis does not have the
Dialogue: 0,0:11:11.05,0:11:16.00,Default,,0000,0000,0000,,the characteristics of the organ that it lands in, it keeps the
Dialogue: 0,0:11:16.00,0:11:17.06,Default,,0000,0000,0000,,characteristics of the primary tumor. In other words,
Dialogue: 0,0:11:17.06,0:11:23.06,Default,,0000,0000,0000,,these metastasizing cells are the genetic progeny
Dialogue: 0,0:11:23.06,0:11:29.00,Default,,0000,0000,0000,,of the primary, so they're going to look like it. If the neoplasm
Dialogue: 0,0:11:29.00,0:11:32.04,Default,,0000,0000,0000,,neoplasm in the primary was making funny\Nglands, the metastasis
Dialogue: 0,0:11:32.04,0:11:36.00,Default,,0000,0000,0000,,will probably make funny glands.
Dialogue: 0,0:11:36.00,0:11:39.06,Default,,0000,0000,0000,,It's a chip off the old block.
Dialogue: 0,0:11:39.06,0:11:43.02,Default,,0000,0000,0000,,That has some some interesting implications there which you'll get into
Dialogue: 0,0:11:43.02,0:11:46.00,Default,,0000,0000,0000,,in future years.
Dialogue: 0,0:11:46.00,0:11:47.03,Default,,0000,0000,0000,,But just
Dialogue: 0,0:11:47.03,0:11:52.01,Default,,0000,0000,0000,,think of it as as a process whereby a single primary can give rise to many metastases.
Dialogue: 0,0:11:52.01,0:11:54.02,Default,,0000,0000,0000,,They can be
Dialogue: 0,0:11:54.02,0:11:57.02,Default,,0000,0000,0000,,at a great distance, it can be four feet away from
Dialogue: 0,0:11:57.02,0:11:59.03,Default,,0000,0000,0000,,the primary and
Dialogue: 0,0:11:59.03,0:12:00.06,Default,,0000,0000,0000,,it can
Dialogue: 0,0:12:00.06,0:12:02.88,Default,,0000,0000,0000,,be very devastating and I will show you
Dialogue: 0,0:12:02.88,0:12:06.03,Default,,0000,0000,0000,,some examples of this.
Dialogue: 0,0:12:06.03,0:12:11.01,Default,,0000,0000,0000,,This is carcinomatosis which refers to a diffuse spread
Dialogue: 0,0:12:11.01,0:12:11.06,Default,,0000,0000,0000,,of
Dialogue: 0,0:12:11.06,0:12:13.03,Default,,0000,0000,0000,,cancer.
Dialogue: 0,0:12:13.03,0:12:17.07,Default,,0000,0000,0000,,This was the lining of the diaphragm, in other words if i took a piece of diaphragm,
Dialogue: 0,0:12:17.07,0:12:18.07,Default,,0000,0000,0000,,cut it out
Dialogue: 0,0:12:18.07,0:12:19.33,Default,,0000,0000,0000,,and you're
Dialogue: 0,0:12:19.33,0:12:22.10,Default,,0000,0000,0000,,looking at the under surface of the diaphragm lined by peritoneum,
Dialogue: 0,0:12:22.10,0:12:23.09,Default,,0000,0000,0000,,
Dialogue: 0,0:12:23.09,0:12:27.04,Default,,0000,0000,0000,,this was from a patient with ovarian cancer,
Dialogue: 0,0:12:27.04,0:12:30.04,Default,,0000,0000,0000,,and every one of these little plaques is a
Dialogue: 0,0:12:30.04,0:12:33.05,Default,,0000,0000,0000,,few million cancer cells growing as a direct
Dialogue: 0,0:12:33.05,0:12:36.09,Default,,0000,0000,0000,,metastasis.
Dialogue: 0,0:12:36.09,0:12:41.08,Default,,0000,0000,0000,,Now I'm going to give you a long shaggy dog\Nstory, here is a
Dialogue: 0,0:12:41.08,0:12:44.00,Default,,0000,0000,0000,,specimen of peritoneum,
Dialogue: 0,0:12:44.00,0:12:47.10,Default,,0000,0000,0000,,this is if I took a couple of pieces of body wall
Dialogue: 0,0:12:47.10,0:12:51.00,Default,,0000,0000,0000,,cut them out and you're looking at the\Nperitoneal surface
Dialogue: 0,0:12:51.00,0:12:53.07,Default,,0000,0000,0000,,of the inside of those pieces
Dialogue: 0,0:12:53.07,0:12:55.01,Default,,0000,0000,0000,,and you can see studded
Dialogue: 0,0:12:55.01,0:12:58.00,Default,,0000,0000,0000,,with a couple a hundred little tiny black
Dialogue: 0,0:12:58.00,0:13:01.08,Default,,0000,0000,0000,,spots and here it's actually become kind of almost a confluent
Dialogue: 0,0:13:01.08,0:13:04.07,Default,,0000,0000,0000,,sheet of neoplasm.
Dialogue: 0,0:13:04.07,0:13:05.05,Default,,0000,0000,0000,,And
Dialogue: 0,0:13:05.05,0:13:08.04,Default,,0000,0000,0000,,you'd say yeah this looks like
Dialogue: 0,0:13:08.04,0:13:14.04,Default,,0000,0000,0000,,many little nodules, why do you suppose it's black like that?
Dialogue: 0,0:13:14.04,0:13:18.02,Default,,0000,0000,0000,,Any thoughts?
Dialogue: 0,0:13:18.02,0:13:22.10,Default,,0000,0000,0000,,Well, the cells are making melanin, this is a\Nmalignant melanoma
Dialogue: 0,0:13:22.10,0:13:25.02,Default,,0000,0000,0000,,which may have heard about. Now
Dialogue: 0,0:13:25.02,0:13:26.02,Default,,0000,0000,0000,,I'm
Dialogue: 0,0:13:26.02,0:13:29.08,Default,,0000,0000,0000,,getting ahead of your knowledge of histology, but there are no cells in the
Dialogue: 0,0:13:29.08,0:13:31.06,Default,,0000,0000,0000,,peritoneum that make
Dialogue: 0,0:13:31.06,0:13:36.08,Default,,0000,0000,0000,,melanin normally, so that means these are visitors from somewhere else,
Dialogue: 0,0:13:36.08,0:13:38.02,Default,,0000,0000,0000,,so clearly just by
Dialogue: 0,0:13:38.02,0:13:41.03,Default,,0000,0000,0000,,the sheer numbers and by the fact that it's melanoma
Dialogue: 0,0:13:41.03,0:13:45.05,Default,,0000,0000,0000,,we can say that these are metastases from somewhere else.
Dialogue: 0,0:13:45.05,0:13:49.10,Default,,0000,0000,0000,,I'll let the plot thicken a little bit, here was the liver
Dialogue: 0,0:13:49.10,0:13:52.06,Default,,0000,0000,0000,,from the same case.
Dialogue: 0,0:13:52.06,0:13:57.04,Default,,0000,0000,0000,,The normal liver is studded with probably thousands of metastases.
Dialogue: 0,0:13:57.04,0:13:59.10,Default,,0000,0000,0000,,This is grown together in a big, horrible
Dialogue: 0,0:13:59.10,0:14:04.01,Default,,0000,0000,0000,,mass which had broken through the hepatic capsule,
Dialogue: 0,0:14:04.01,0:14:08.39,Default,,0000,0000,0000,,and the normal liver does not contain melanin producing cells.
Dialogue: 0,0:14:08.39,0:14:12.02,Default,,0000,0000,0000,,That fact and the fact that that these\Nare so multiple
Dialogue: 0,0:14:12.02,0:14:16.09,Default,,0000,0000,0000,,says that this liver is riddled with hematogenous metastases.
Dialogue: 0,0:14:16.09,0:14:21.05,Default,,0000,0000,0000,,Where do you think the primary was?
Dialogue: 0,0:14:21.05,0:14:23.03,Default,,0000,0000,0000,,Someone said it.
Dialogue: 0,0:14:23.03,0:14:25.00,Default,,0000,0000,0000,,Skin. That'd be your first bet.
Dialogue: 0,0:14:25.00,0:14:28.00,Default,,0000,0000,0000,,Because melanoma is a common story.
Dialogue: 0,0:14:28.00,0:14:32.02,Default,,0000,0000,0000,,But you're wrong. Eyeball.
Dialogue: 0,0:14:32.02,0:14:36.03,Default,,0000,0000,0000,,This is a bad picture, I screwed up and am\Nnot a photographer, but there you see the
Dialogue: 0,0:14:36.03,0:14:38.46,Default,,0000,0000,0000,,reflex from the flash, but just behind it
Dialogue: 0,0:14:38.46,0:14:39.05,Default,,0000,0000,0000,,there's a little lump
Dialogue: 0,0:14:39.05,0:14:40.06,Default,,0000,0000,0000,,there
Dialogue: 0,0:14:40.06,0:14:43.06,Default,,0000,0000,0000,,and that is the primary neoplasm.
Dialogue: 0,0:14:43.06,0:14:46.03,Default,,0000,0000,0000,,Now this tells another story.
Dialogue: 0,0:14:46.03,0:14:49.06,Default,,0000,0000,0000,,This patient presented with a visual disturbance and the ophthalmologist saw this
Dialogue: 0,0:14:49.06,0:14:51.08,Default,,0000,0000,0000,,and said this eyeball has to come out.
Dialogue: 0,0:14:51.08,0:14:53.00,Default,,0000,0000,0000,,And the eyeball was taken out.
Dialogue: 0,0:14:53.00,0:14:56.08,Default,,0000,0000,0000,,It is our job as pathologist to assess\Nwhether the excision
Dialogue: 0,0:14:56.08,0:14:59.04,Default,,0000,0000,0000,,has been complete.
Dialogue: 0,0:14:59.04,0:15:03.09,Default,,0000,0000,0000,,And so we sample the various coats of the eye thoroughly to see if the melanoma
Dialogue: 0,0:15:03.09,0:15:07.00,Default,,0000,0000,0000,,cells had penetrated through and if there any left in the in the orbit.
Dialogue: 0,0:15:07.00,0:15:07.07,Default,,0000,0000,0000,,And the answer
Dialogue: 0,0:15:07.07,0:15:09.03,Default,,0000,0000,0000,,to it is no.
Dialogue: 0,0:15:09.03,0:15:12.08,Default,,0000,0000,0000,,Looks clean.
Dialogue: 0,0:15:12.08,0:15:16.00,Default,,0000,0000,0000,,I hope the surgeon didn't say this but this sometimes gives rise to the statement:
Dialogue: 0,0:15:16.00,0:15:18.10,Default,,0000,0000,0000,,we got it all!
Dialogue: 0,0:15:18.10,0:15:23.04,Default,,0000,0000,0000,,Now this patient did fine after removal\Nof the eyeball, did fine for several years.
Dialogue: 0,0:15:23.04,0:15:24.05,Default,,0000,0000,0000,,With
Dialogue: 0,0:15:24.05,0:15:27.08,Default,,0000,0000,0000,,absolutely no evidence of metastases.
Dialogue: 0,0:15:27.08,0:15:31.05,Default,,0000,0000,0000,,Then something happened, God knows what,
Dialogue: 0,0:15:31.05,0:15:32.06,Default,,0000,0000,0000,,the patient just
Dialogue: 0,0:15:32.06,0:15:34.09,Default,,0000,0000,0000,,went downhill within a period of weeks and died
Dialogue: 0,0:15:34.09,0:15:37.08,Default,,0000,0000,0000,,and had metastases all over the\Nbody.
Dialogue: 0,0:15:37.08,0:15:41.08,Default,,0000,0000,0000,,That brings up another interesting point which I'll just tease you with and
Dialogue: 0,0:15:41.08,0:15:45.00,Default,,0000,0000,0000,,that's the phenomenon we call dormancy.
Dialogue: 0,0:15:45.00,0:15:49.06,Default,,0000,0000,0000,,It was very clear from the story
Dialogue: 0,0:15:49.06,0:15:52.00,Default,,0000,0000,0000,,that we had taken out the primary
Dialogue: 0,0:15:52.00,0:15:55.04,Default,,0000,0000,0000,,and there was never any recurrence in\Nthe orbit and so that what that says is
Dialogue: 0,0:15:55.04,0:15:58.03,Default,,0000,0000,0000,,these melanoma cells have gotten into\Ncirculation
Dialogue: 0,0:15:58.03,0:16:02.08,Default,,0000,0000,0000,,that there were tiny occult metastases
Dialogue: 0,0:16:02.08,0:16:05.04,Default,,0000,0000,0000,,at the time the eyeball was taken out
Dialogue: 0,0:16:05.04,0:16:07.01,Default,,0000,0000,0000,,and they chose not to grow
Dialogue: 0,0:16:07.01,0:16:08.09,Default,,0000,0000,0000,,for several years
Dialogue: 0,0:16:08.09,0:16:12.00,Default,,0000,0000,0000,,and then something changed and they grew.
Dialogue: 0,0:16:12.00,0:16:14.03,Default,,0000,0000,0000,,And we see that sometimes.
Dialogue: 0,0:16:14.03,0:16:18.47,Default,,0000,0000,0000,,In other words earth eighteen months survival or two years survival or five year survival
Dialogue: 0,0:16:18.47,0:16:20.10,Default,,0000,0000,0000,,is a statistical thing, but
Dialogue: 0,0:16:20.10,0:16:22.08,Default,,0000,0000,0000,,sometimes
Dialogue: 0,0:16:22.08,0:16:23.09,Default,,0000,0000,0000,,it doesn't
Dialogue: 0,0:16:23.09,0:16:25.05,Default,,0000,0000,0000,,matter.
Dialogue: 0,0:16:25.05,0:16:27.06,Default,,0000,0000,0000,,So this illustrates
Dialogue: 0,0:16:27.06,0:16:31.08,Default,,0000,0000,0000,,the fact that that metastases can be very distant from the primary,
Dialogue: 0,0:16:31.08,0:16:32.06,Default,,0000,0000,0000,,they can
Dialogue: 0,0:16:32.06,0:16:33.60,Default,,0000,0000,0000,,
Dialogue: 0,0:16:33.60,0:16:34.10,Default,,0000,0000,0000,,be
Dialogue: 0,0:16:34.10,0:16:38.02,Default,,0000,0000,0000,,millions of metastases from one primary
Dialogue: 0,0:16:38.02,0:16:42.08,Default,,0000,0000,0000,,and also I threw in this whole\Nphenomenon of dormancy which is a bit unusual
Dialogue: 0,0:16:42.08,0:16:44.06,Default,,0000,0000,0000,,but it happens.
Dialogue: 0,0:16:44.06,0:16:46.06,Default,,0000,0000,0000,,I'll show you some other mets.
Dialogue: 0,0:16:46.06,0:16:48.07,Default,,0000,0000,0000,,Here's a lung of a youngster.
Dialogue: 0,0:16:48.07,0:16:52.07,Default,,0000,0000,0000,,Every one of these is a nodule of neoplasm, the other lung looked just like this.
Dialogue: 0,0:16:52.07,0:16:53.06,Default,,0000,0000,0000,,This happens
Dialogue: 0,0:16:53.06,0:16:57.01,Default,,0000,0000,0000,,to have been a primary in the kidney which
Dialogue: 0,0:16:57.01,0:17:00.00,Default,,0000,0000,0000,,got to the lungs through the renal veins, the vena cava, and on up.
Dialogue: 0,0:17:00.00,0:17:01.01,Default,,0000,0000,0000,,
Dialogue: 0,0:17:01.01,0:17:05.03,Default,,0000,0000,0000,,The good news is that we can cure many of these, not {\i1}at{\i0} this stage, but we
Dialogue: 0,0:17:05.03,0:17:06.96,Default,,0000,0000,0000,,can prevent it from reaching this
Dialogue: 0,0:17:06.96,0:17:10.03,Default,,0000,0000,0000,,stage now.
Dialogue: 0,0:17:10.03,0:17:14.01,Default,,0000,0000,0000,,Here's an interesting one that we see very often, this is a vertebral column which
Dialogue: 0,0:17:14.01,0:17:17.04,Default,,0000,0000,0000,,I sliced in a band saw
Dialogue: 0,0:17:17.04,0:17:20.10,Default,,0000,0000,0000,,so you're looking at a couple of mirror\Nimages and this is a pretty normal
Dialogue: 0,0:17:20.10,0:17:24.05,Default,,0000,0000,0000,,vertebra up here, this is an intervertebral disc up here.
Dialogue: 0,0:17:24.05,0:17:28.02,Default,,0000,0000,0000,,These two lower vertebrae you see these whitish areas
Dialogue: 0,0:17:28.02,0:17:28.08,Default,,0000,0000,0000,,here and here.
Dialogue: 0,0:17:28.08,0:17:30.09,Default,,0000,0000,0000,,These were very
Dialogue: 0,0:17:30.09,0:17:34.05,Default,,0000,0000,0000,,dense bone, and interestingly
Dialogue: 0,0:17:34.05,0:17:38.03,Default,,0000,0000,0000,,what this represents is metastasis to the bone,
Dialogue: 0,0:17:38.03,0:17:42.03,Default,,0000,0000,0000,,it stimulates bone formation around the cancer cells, it's something
Dialogue: 0,0:17:42.03,0:17:45.02,Default,,0000,0000,0000,,we call an osteoblastic
Dialogue: 0,0:17:45.02,0:17:46.05,Default,,0000,0000,0000,,phenomenon
Dialogue: 0,0:17:46.05,0:17:47.03,Default,,0000,0000,0000,,or an osteoblastic metastasis.
Dialogue: 0,0:17:47.03,0:17:48.00,Default,,0000,0000,0000,,This would have shown up
Dialogue: 0,0:17:48.00,0:17:51.03,Default,,0000,0000,0000,,as a density on the x-ray
Dialogue: 0,0:17:51.03,0:17:55.09,Default,,0000,0000,0000,,under the microscope, there's a lot of bone there\Nbut cancer cells throughout
Dialogue: 0,0:17:55.09,0:17:59.01,Default,,0000,0000,0000,,and usually cancer cells reach the bone
Dialogue: 0,0:17:59.01,0:18:01.03,Default,,0000,0000,0000,,via the hematogenous route.
Dialogue: 0,0:18:01.03,0:18:04.09,Default,,0000,0000,0000,,Could be anything, I mean if someone showed\Nme this, I'd say it's metastatic something or other
Dialogue: 0,0:18:04.09,0:18:07.08,Default,,0000,0000,0000,,from somewhere or other
Dialogue: 0,0:18:07.08,0:18:09.93,Default,,0000,0000,0000,,but you will learn for instance that\Nbreast
Dialogue: 0,0:18:09.93,0:18:14.08,Default,,0000,0000,0000,,very often breast cancer very often goes\Nto bone. Prostate cancer notoriously goes to bone.
Dialogue: 0,0:18:14.08,0:18:16.06,Default,,0000,0000,0000,,
Dialogue: 0,0:18:16.06,0:18:20.04,Default,,0000,0000,0000,,I won't bore you with the list, but you're going to learn as you study oncology
Dialogue: 0,0:18:20.04,0:18:21.10,Default,,0000,0000,0000,,what the likelihood of
Dialogue: 0,0:18:21.10,0:18:24.02,Default,,0000,0000,0000,,I mean if this came from a
Dialogue: 0,0:18:24.02,0:18:26.03,Default,,0000,0000,0000,,middle-aged woman with
Dialogue: 0,0:18:26.03,0:18:30.02,Default,,0000,0000,0000,,with a breast nodule, I'd say breast cancer. If it came from an elderly guy with
Dialogue: 0,0:18:30.02,0:18:34.02,Default,,0000,0000,0000,,urinary tract obstruction, I'd say look at his prostate.
Dialogue: 0,0:18:34.02,0:18:38.02,Default,,0000,0000,0000,,So that is an osteoblastic kind of metastasis.
Dialogue: 0,0:18:38.02,0:18:41.00,Default,,0000,0000,0000,,Here is a different one,
Dialogue: 0,0:18:41.00,0:18:43.01,Default,,0000,0000,0000,,this one has another story associated with it.
Dialogue: 0,0:18:43.01,0:18:46.02,Default,,0000,0000,0000,,This was a 42-year old guy
Dialogue: 0,0:18:46.02,0:18:49.09,Default,,0000,0000,0000,,who came in with back pain and he was a\Nmanual laborer that did heavy labor
Dialogue: 0,0:18:49.09,0:18:53.08,Default,,0000,0000,0000,,and everyone thought at first well you\Nknow it's some orthopedic
Dialogue: 0,0:18:53.08,0:18:54.04,Default,,0000,0000,0000,,injury
Dialogue: 0,0:18:54.04,0:18:57.89,Default,,0000,0000,0000,,until they got an x-ray of his back and\Ndiscovered that one of the vertebrae was
Dialogue: 0,0:18:57.89,0:18:59.06,Default,,0000,0000,0000,,essentially turned to mush.
Dialogue: 0,0:18:59.06,0:19:01.10,Default,,0000,0000,0000,,Here's a normal vertebra here and here.
Dialogue: 0,0:19:01.10,0:19:04.04,Default,,0000,0000,0000,,Here's a disc and this is a
Dialogue: 0,0:19:04.04,0:19:08.02,Default,,0000,0000,0000,,osteolytic metastasis, it turned out that there was a metastasis
Dialogue: 0,0:19:08.02,0:19:13.01,Default,,0000,0000,0000,,that completely destroyed the bone and it simply collapsed.
Dialogue: 0,0:19:13.01,0:19:18.01,Default,,0000,0000,0000,,Now this man presented because of his metastasis, that sometimes happens,
Dialogue: 0,0:19:18.01,0:19:20.07,Default,,0000,0000,0000,,it may not be the primary, it turned out he was a\Nheavy smoker
Dialogue: 0,0:19:20.07,0:19:22.06,Default,,0000,0000,0000,,and had a small,
Dialogue: 0,0:19:22.06,0:19:24.06,Default,,0000,0000,0000,,inapparent
Dialogue: 0,0:19:24.06,0:19:27.08,Default,,0000,0000,0000,,bronchogenic primary, in other words, a\Nlung cancer
Dialogue: 0,0:19:27.08,0:19:31.01,Default,,0000,0000,0000,,and it metastasize to his bone without even causing any ruckus.
Dialogue: 0,0:19:31.01,0:19:35.10,Default,,0000,0000,0000,,He probably had a little cough as all smokers do
Dialogue: 0,0:19:35.10,0:19:36.08,Default,,0000,0000,0000,,
Dialogue: 0,0:19:36.08,0:19:38.05,Default,,0000,0000,0000,,but presented because of the metastasis
Dialogue: 0,0:19:38.05,0:19:41.02,Default,,0000,0000,0000,,This was
Dialogue: 0,0:19:41.02,0:19:44.07,Default,,0000,0000,0000,,another smoker incidence, I remember
Dialogue: 0,0:19:44.07,0:19:47.02,Default,,0000,0000,0000,,this one very well,
Dialogue: 0,0:19:47.02,0:19:49.04,Default,,0000,0000,0000,,the patient came in convulsing, signs of
Dialogue: 0,0:19:49.04,0:19:52.08,Default,,0000,0000,0000,,increased intracranial pressure.
Dialogue: 0,0:19:52.08,0:19:53.07,Default,,0000,0000,0000,,They
Dialogue: 0,0:19:53.07,0:19:57.06,Default,,0000,0000,0000,,had to take him to the operating room very quickly to decompress the brain
Dialogue: 0,0:19:57.06,0:20:00.00,Default,,0000,0000,0000,,and save him from dying from
Dialogue: 0,0:20:00.00,0:20:02.04,Default,,0000,0000,0000,,the pressure and
Dialogue: 0,0:20:02.04,0:20:04.02,Default,,0000,0000,0000,,my colleague
Dialogue: 0,0:20:04.02,0:20:06.09,Default,,0000,0000,0000,,sent me a piece of this
Dialogue: 0,0:20:06.09,0:20:10.04,Default,,0000,0000,0000,,to look at it quickly with what we call\Na frozen section. You freeze a tissue and
Dialogue: 0,0:20:10.04,0:20:12.00,Default,,0000,0000,0000,,make a quick section of it
Dialogue: 0,0:20:12.00,0:20:14.05,Default,,0000,0000,0000,,It was easy to say this isn't
Dialogue: 0,0:20:14.05,0:20:16.08,Default,,0000,0000,0000,,cancer arising in the brain
Dialogue: 0,0:20:16.08,0:20:19.06,Default,,0000,0000,0000,,because it didn't look like that. It looked like a cancer that came from somewhere else.
Dialogue: 0,0:20:19.06,0:20:22.07,Default,,0000,0000,0000,,This is not rocket science, you'll learn how to do it in the spring.
Dialogue: 0,0:20:22.07,0:20:23.06,Default,,0000,0000,0000,,
Dialogue: 0,0:20:23.06,0:20:24.78,Default,,0000,0000,0000,,But it's because the
Dialogue: 0,0:20:24.78,0:20:29.07,Default,,0000,0000,0000,,metastasis resembles the primary that we\Nlooked at it and said, no, this isn't brain, this is
Dialogue: 0,0:20:29.07,0:20:32.00,Default,,0000,0000,0000,,metastasis to the brain.
Dialogue: 0,0:20:32.00,0:20:36.05,Default,,0000,0000,0000,,Poor fellow died shortly after operation, it turned out again he was riddled with metastases
Dialogue: 0,0:20:36.05,0:20:38.05,Default,,0000,0000,0000,,with a small lung primary.
Dialogue: 0,0:20:38.05,0:20:40.06,Default,,0000,0000,0000,,Lung primary
Dialogue: 0,0:20:40.06,0:20:42.01,Default,,0000,0000,0000,,very often goes to brain like that.
Dialogue: 0,0:20:42.01,0:20:44.10,Default,,0000,0000,0000,,Oh
Dialogue: 0,0:20:44.10,0:20:49.05,Default,,0000,0000,0000,,one last lovely image
Dialogue: 0,0:20:49.05,0:20:52.03,Default,,0000,0000,0000,,there is a liver
Dialogue: 0,0:20:52.03,0:20:54.04,Default,,0000,0000,0000,,riddled with metastases.
Dialogue: 0,0:20:54.04,0:20:56.09,Default,,0000,0000,0000,,And if
Dialogue: 0,0:20:56.09,0:21:00.03,Default,,0000,0000,0000,,someone showed me this liver and said where did this come from, I'd say
Dialogue: 0,0:21:00.03,0:21:03.02,Default,,0000,0000,0000,,gee, well look at the GI tract.
Dialogue: 0,0:21:03.02,0:21:06.07,Default,,0000,0000,0000,,It can be elsewhere, this was a lung\Ncancer
Dialogue: 0,0:21:06.07,0:21:10.08,Default,,0000,0000,0000,,that had metastasized and gotten into the bloodstream, had gotten around and liked the taste
Dialogue: 0,0:21:10.08,0:21:12.00,Default,,0000,0000,0000,,of liver
Dialogue: 0,0:21:12.00,0:21:15.08,Default,,0000,0000,0000,,and produced metastases in the liver. There were metastases in many other
Dialogue: 0,0:21:15.08,0:21:17.01,Default,,0000,0000,0000,,places as well.
Dialogue: 0,0:21:17.01,0:21:19.01,Default,,0000,0000,0000,,Well, i guess that
Dialogue: 0,0:21:19.01,0:21:25.02,Default,,0000,0000,0000,,gives you a little bit of an example, a little bit\Nof a feeling for the the destructiveness
Dialogue: 0,0:21:25.02,0:21:28.04,Default,,0000,0000,0000,,of this process of metastasis. Again benign neoplasm
Dialogue: 0,0:21:28.04,0:21:31.06,Default,,0000,0000,0000,,do not metastasize, only malignant
Dialogue: 0,0:21:31.06,0:21:33.06,Default,,0000,0000,0000,,ones do.
Dialogue: 0,0:21:33.06,0:21:44.01,Default,,0000,0000,0000,,Benign neoplasms do not invade, only malignant ones.
Dialogue: 0,0:21:44.01,0:22:00.04,Default,,0000,0000,0000,,
Dialogue: 0,0:22:00.04,0:22:03.05,Default,,0000,0000,0000,,With
Dialogue: 0,0:22:03.05,0:22:06.05,Default,,0000,0000,0000,,those concepts
Dialogue: 0,0:22:06.05,0:22:09.92,Default,,0000,0000,0000,,of neoplasia, hope you've all got benign and malignant invasion, metastasis sort of
Dialogue: 0,0:22:09.92,0:22:11.04,Default,,0000,0000,0000,,under your belts.
Dialogue: 0,0:22:11.04,0:22:18.02,Default,,0000,0000,0000,,I want to talk for a little bit on how neoplasms are
Dialogue: 0,0:22:18.02,0:22:20.03,Default,,0000,0000,0000,,put together microscopically.
Dialogue: 0,0:22:20.03,0:22:23.90,Default,,0000,0000,0000,,Again, don't worry about being able\Nto do this kind of diagnosis yourself,
Dialogue: 0,0:22:23.90,0:22:25.09,Default,,0000,0000,0000,,just listen to the concepts.
Dialogue: 0,0:22:25.09,0:22:28.05,Default,,0000,0000,0000,,I want to review the concept of stroma,
Dialogue: 0,0:22:28.05,0:22:30.01,Default,,0000,0000,0000,,the concept of differentiation,
Dialogue: 0,0:22:30.01,0:22:33.00,Default,,0000,0000,0000,,and ideas of grading
Dialogue: 0,0:22:33.00,0:22:36.04,Default,,0000,0000,0000,,and staging.
Dialogue: 0,0:22:36.04,0:22:41.09,Default,,0000,0000,0000,,All right, let's let's begin with the\Nbusiness of stroma and angiogenesis.
Dialogue: 0,0:22:41.09,0:22:43.09,Default,,0000,0000,0000,,One of things that I should emphasize
Dialogue: 0,0:22:43.09,0:22:48.00,Default,,0000,0000,0000,,that I didn't really emphasize so far is that
Dialogue: 0,0:22:48.00,0:22:50.06,Default,,0000,0000,0000,,a given module of neoplasm
Dialogue: 0,0:22:50.06,0:22:53.08,Default,,0000,0000,0000,,take one of those metastases in the liver for\Ninstance
Dialogue: 0,0:22:53.08,0:22:55.09,Default,,0000,0000,0000,,A given nodule of neoplasm
Dialogue: 0,0:22:55.09,0:22:57.06,Default,,0000,0000,0000,,is just not a spherical
Dialogue: 0,0:22:57.06,0:23:03.00,Default,,0000,0000,0000,,collection of 100% cancer cells.
Dialogue: 0,0:23:03.00,0:23:05.01,Default,,0000,0000,0000,,This is a very important concept
Dialogue: 0,0:23:05.01,0:23:06.04,Default,,0000,0000,0000,,and it makes perfect sense
Dialogue: 0,0:23:06.04,0:23:08.03,Default,,0000,0000,0000,,because
Dialogue: 0,0:23:08.03,0:23:10.29,Default,,0000,0000,0000,,you could not possibly grow
Dialogue: 0,0:23:10.29,0:23:11.06,Default,,0000,0000,0000,,a lump literally that big
Dialogue: 0,0:23:11.06,0:23:12.09,Default,,0000,0000,0000,,and have
Dialogue: 0,0:23:12.09,0:23:14.07,Default,,0000,0000,0000,,a blood supply
Dialogue: 0,0:23:14.07,0:23:17.03,Default,,0000,0000,0000,,for the cells in the center,
Dialogue: 0,0:23:17.03,0:23:18.04,Default,,0000,0000,0000,,you follow me?
Dialogue: 0,0:23:18.04,0:23:20.04,Default,,0000,0000,0000,,In other words, if they were pure cancer cells
Dialogue: 0,0:23:20.04,0:23:22.01,Default,,0000,0000,0000,,the blood would be out here
Dialogue: 0,0:23:22.01,0:23:24.04,Default,,0000,0000,0000,,and the cells would be proliferating here.
Dialogue: 0,0:23:24.04,0:23:29.06,Default,,0000,0000,0000,,It doesn't work that way, the cancer\Nneeds a blood supply in order to grow.
Dialogue: 0,0:23:29.06,0:23:30.05,Default,,0000,0000,0000,,and it turns
Dialogue: 0,0:23:30.05,0:23:31.10,Default,,0000,0000,0000,,out that
Dialogue: 0,0:23:31.10,0:23:34.02,Default,,0000,0000,0000,,cancers
Dialogue: 0,0:23:34.02,0:23:38.04,Default,,0000,0000,0000,,are able and this is an very interesting\Nphenomenon
Dialogue: 0,0:23:38.04,0:23:39.08,Default,,0000,0000,0000,,to
Dialogue: 0,0:23:39.08,0:23:43.00,Default,,0000,0000,0000,,induce the formation of what we call\Na stroma
Dialogue: 0,0:23:43.00,0:23:45.06,Default,,0000,0000,0000,,it's a fibrous
Dialogue: 0,0:23:45.06,0:23:49.00,Default,,0000,0000,0000,,particularly a vascular\Nframework
Dialogue: 0,0:23:49.00,0:23:52.00,Default,,0000,0000,0000,,which supports the neoplasm.
Dialogue: 0,0:23:52.00,0:23:54.01,Default,,0000,0000,0000,,Now the stroma
Dialogue: 0,0:23:54.01,0:23:56.05,Default,,0000,0000,0000,,is not part of the malignant clone
Dialogue: 0,0:23:56.05,0:23:59.07,Default,,0000,0000,0000,,or the neoplastic clone.
Dialogue: 0,0:23:59.07,0:24:00.10,Default,,0000,0000,0000,,It comes from
Dialogue: 0,0:24:00.10,0:24:06.07,Default,,0000,0000,0000,,the connective tissue cells and the blood vessels cells
Dialogue: 0,0:24:06.07,0:24:07.01,Default,,0000,0000,0000,,around
Dialogue: 0,0:24:07.01,0:24:09.00,Default,,0000,0000,0000,,the neoplasm.
Dialogue: 0,0:24:09.00,0:24:11.03,Default,,0000,0000,0000,,The neoplastic cells
Dialogue: 0,0:24:11.03,0:24:14.09,Default,,0000,0000,0000,,and probably some of the inflammatory\Ncells accompanying the neoplasm are able
Dialogue: 0,0:24:14.09,0:24:16.05,Default,,0000,0000,0000,,to induce
Dialogue: 0,0:24:16.05,0:24:19.06,Default,,0000,0000,0000,,the formation of this stroma. It's
Dialogue: 0,0:24:19.06,0:24:20.05,Default,,0000,0000,0000,,very much
Dialogue: 0,0:24:20.05,0:24:24.06,Default,,0000,0000,0000,,like the the induction of granulation\Ntissue which you're very familiar with from
Dialogue: 0,0:24:24.06,0:24:25.03,Default,,0000,0000,0000,,last week.
Dialogue: 0,0:24:25.03,0:24:26.05,Default,,0000,0000,0000,,And
Dialogue: 0,0:24:26.05,0:24:27.24,Default,,0000,0000,0000,,what
Dialogue: 0,0:24:27.24,0:24:28.78,Default,,0000,0000,0000,,happens
Dialogue: 0,0:24:28.78,0:24:34.92,Default,,0000,0000,0000,,is this fibrous and vascular stroma grows into the nodule and enables it
Dialogue: 0,0:24:34.92,0:24:36.04,Default,,0000,0000,0000,,to proliferate.
Dialogue: 0,0:24:36.04,0:24:37.05,Default,,0000,0000,0000,,
Dialogue: 0,0:24:37.05,0:24:39.09,Default,,0000,0000,0000,,Now we talk about
Dialogue: 0,0:24:39.09,0:24:45.08,Default,,0000,0000,0000,,tumor angiogenesis, I mean the emphasis being\Non the blood vessels.
Dialogue: 0,0:24:45.08,0:24:48.10,Default,,0000,0000,0000,,There is abundant
Dialogue: 0,0:24:48.10,0:24:50.79,Default,,0000,0000,0000,,experimental evidence to show
Dialogue: 0,0:24:50.79,0:24:51.09,Default,,0000,0000,0000,,that
Dialogue: 0,0:24:51.09,0:24:55.28,Default,,0000,0000,0000,,and i won't go into the details, but if\Nyou create a situation where you got
Dialogue: 0,0:24:55.28,0:24:58.05,Default,,0000,0000,0000,,a bunch of neoplastic cells growing\Npure
Dialogue: 0,0:24:58.05,0:25:01.05,Default,,0000,0000,0000,,where they can't pick up a stroma,
Dialogue: 0,0:25:01.05,0:25:06.02,Default,,0000,0000,0000,,the module will never get bigger than a\Nmillimeter or two at the very most,
Dialogue: 0,0:25:06.02,0:25:07.00,Default,,0000,0000,0000,,probably less because
Dialogue: 0,0:25:07.00,0:25:12.03,Default,,0000,0000,0000,,because the oxygen and nutrients cannot\Ndiffuse in the solid mass any further.
Dialogue: 0,0:25:12.03,0:25:14.03,Default,,0000,0000,0000,,There are many experiments that show
Dialogue: 0,0:25:14.03,0:25:19.01,Default,,0000,0000,0000,,you grow neoplastic cells in these\Nlittle balls and they stopped growing.
Dialogue: 0,0:25:19.01,0:25:23.00,Default,,0000,0000,0000,,and then if you do something to induce\Nangiogenesis, BOOM,
Dialogue: 0,0:25:23.00,0:25:24.08,Default,,0000,0000,0000,,as soon as they pick up
Dialogue: 0,0:25:24.08,0:25:27.02,Default,,0000,0000,0000,,the vascular stroma
Dialogue: 0,0:25:27.02,0:25:28.12,Default,,0000,0000,0000,,they begin
Dialogue: 0,0:25:28.12,0:25:29.02,Default,,0000,0000,0000,,to grow
Dialogue: 0,0:25:29.02,0:25:33.00,Default,,0000,0000,0000,,so tumor angiogenesis is exceedingly important. You can
Dialogue: 0,0:25:33.00,0:25:34.04,Default,,0000,0000,0000,,read a
Dialogue: 0,0:25:34.04,0:25:38.05,Default,,0000,0000,0000,,I won't bother you with the details, but we are\Nbeginning to know a little bit about how
Dialogue: 0,0:25:38.05,0:25:43.00,Default,,0000,0000,0000,,this is mediated and what it looks like\Nis this:
Dialogue: 0,0:25:43.00,0:25:44.08,Default,,0000,0000,0000,,again without too much detail
Dialogue: 0,0:25:44.08,0:25:47.04,Default,,0000,0000,0000,,this was a lump in a breast.
Dialogue: 0,0:25:47.04,0:25:51.00,Default,,0000,0000,0000,,This was a breast cancer.
Dialogue: 0,0:25:51.00,0:25:54.02,Default,,0000,0000,0000,,These dark clumps are the cancer cells
Dialogue: 0,0:25:54.02,0:25:56.06,Default,,0000,0000,0000,,and the
Dialogue: 0,0:25:56.06,0:25:58.06,Default,,0000,0000,0000,,pink in the background
Dialogue: 0,0:25:58.06,0:26:00.02,Default,,0000,0000,0000,,is the stroma.
Dialogue: 0,0:26:00.02,0:26:04.08,Default,,0000,0000,0000,,I'll emphasize in particular there is a\Ncapillary there,
Dialogue: 0,0:26:04.08,0:26:08.08,Default,,0000,0000,0000,,there is a capillary cut lengthwise there, there's another capillary here
Dialogue: 0,0:26:08.08,0:26:10.41,Default,,0000,0000,0000,,and so forth
Dialogue: 0,0:26:10.41,0:26:11.04,Default,,0000,0000,0000,,so that any given
Dialogue: 0,0:26:11.04,0:26:15.02,Default,,0000,0000,0000,,clump of cancer cells isn't very far from
Dialogue: 0,0:26:15.02,0:26:17.17,Default,,0000,0000,0000,,a capillary.
Dialogue: 0,0:26:17.17,0:26:19.04,Default,,0000,0000,0000,,That's the concept
Dialogue: 0,0:26:19.04,0:26:23.98,Default,,0000,0000,0000,,of the stroma and tumor angiogenesis and\Nwhat it means.
Dialogue: 0,0:26:23.98,0:26:27.02,Default,,0000,0000,0000,,If we could stop angiogenesis
Dialogue: 0,0:26:27.02,0:26:29.00,Default,,0000,0000,0000,,we could stop tumor growth.
Dialogue: 0,0:26:29.00,0:26:33.02,Default,,0000,0000,0000,,It would be wonderful and some of these\Nattempts have reached the clinical testing
Dialogue: 0,0:26:33.02,0:26:35.02,Default,,0000,0000,0000,,testing stage but nothing terribly dramatic yet.
Dialogue: 0,0:26:35.02,0:26:38.04,Default,,0000,0000,0000,,But it's certainly a handle.
Dialogue: 0,0:26:38.04,0:26:43.01,Default,,0000,0000,0000,,Here is kind of a loose stroma, not very fibrous but a lot of blood vessels.
Dialogue: 0,0:26:43.01,0:26:44.07,Default,,0000,0000,0000,,Sometimes
Dialogue: 0,0:26:44.07,0:26:45.05,Default,,0000,0000,0000,,you can be
Dialogue: 0,0:26:45.05,0:26:47.03,Default,,0000,0000,0000,,very dense.
Dialogue: 0,0:26:47.03,0:26:48.66,Default,,0000,0000,0000,,These are cancer cells
Dialogue: 0,0:26:48.66,0:26:52.05,Default,,0000,0000,0000,,in a very dense collagenous stroma.
Dialogue: 0,0:26:52.05,0:26:54.01,Default,,0000,0000,0000,,This kind of a lump has a
Dialogue: 0,0:26:54.01,0:26:56.04,Default,,0000,0000,0000,,consistency about like wood.
Dialogue: 0,0:26:56.04,0:27:00.07,Default,,0000,0000,0000,,We call that, it's an adjective you'll\Nhear occasionally, it's a scirrhous
Dialogue: 0,0:27:00.07,0:27:02.00,Default,,0000,0000,0000,,s-c-i-r-r-h-o-u-s
Dialogue: 0,0:27:02.00,0:27:05.05,Default,,0000,0000,0000,,scirrhous
Dialogue: 0,0:27:05.05,0:27:07.09,Default,,0000,0000,0000,,mode of growth
Dialogue: 0,0:27:07.09,0:27:11.09,Default,,0000,0000,0000,,But whatever the variation, any
Dialogue: 0,0:27:11.09,0:27:12.07,Default,,0000,0000,0000,,lump of
Dialogue: 0,0:27:12.07,0:27:15.08,Default,,0000,0000,0000,,neoplasm has this vascular stroma
Dialogue: 0,0:27:15.08,0:27:19.02,Default,,0000,0000,0000,,that it has induced.
Dialogue: 0,0:27:19.02,0:27:20.02,Default,,0000,0000,0000,,Okay.
Dialogue: 0,0:27:20.02,0:27:26.02,Default,,0000,0000,0000,,Now go onto the next concept, that is related to the fact that
Dialogue: 0,0:27:26.02,0:27:28.10,Default,,0000,0000,0000,,since neoplastic cells are derived
Dialogue: 0,0:27:28.10,0:27:33.67,Default,,0000,0000,0000,,from a previously normal cell population, they're
Dialogue: 0,0:27:33.67,0:27:37.08,Default,,0000,0000,0000,,going to share many of the genetic traits and are going to have some new ones
Dialogue: 0,0:27:37.08,0:27:41.00,Default,,0000,0000,0000,,because of these mutations but they're going to share a tremendous genetic
Dialogue: 0,0:27:41.00,0:27:42.08,Default,,0000,0000,0000,,background
Dialogue: 0,0:27:42.08,0:27:46.03,Default,,0000,0000,0000,,with the parent issues so\Nthey're going to resemble the parent tissue
Dialogue: 0,0:27:46.03,0:27:49.01,Default,,0000,0000,0000,,to some variable extent.
Dialogue: 0,0:27:49.01,0:27:54.10,Default,,0000,0000,0000,,I mean sometimes very sharp resemblance, sometimes maybe not much of a resemblance.
Dialogue: 0,0:27:54.10,0:27:56.01,Default,,0000,0000,0000,,
Dialogue: 0,0:27:56.01,0:27:58.07,Default,,0000,0000,0000,,When the neoplastic tissue
Dialogue: 0,0:27:58.07,0:28:03.04,Default,,0000,0000,0000,,resembles the parental tissue, the normal tissue,
Dialogue: 0,0:28:03.04,0:28:05.40,Default,,0000,0000,0000,,through a high degree
Dialogue: 0,0:28:05.40,0:28:09.09,Default,,0000,0000,0000,,very close resemblance we speak about\Nthat neoplasm as being well-differentiated.
Dialogue: 0,0:28:09.09,0:28:13.00,Default,,0000,0000,0000,,Funny phrase, I didn't invent it.
Dialogue: 0,0:28:13.00,0:28:18.04,Default,,0000,0000,0000,,When we say well differentiated, it means\Nlooks just like mom and pop.
Dialogue: 0,0:28:18.04,0:28:22.02,Default,,0000,0000,0000,,On the other extreme, it may look\Nnothing, I'll show you some examples,
Dialogue: 0,0:28:22.02,0:28:26.02,Default,,0000,0000,0000,,it may look nothing like the parental\Ntissue, we say that is a poorly differentiated
Dialogue: 0,0:28:26.02,0:28:27.41,Default,,0000,0000,0000,,or
Dialogue: 0,0:28:27.41,0:28:32.03,Default,,0000,0000,0000,,undifferentiated
Dialogue: 0,0:28:32.03,0:28:32.08,Default,,0000,0000,0000,,tissue.
Dialogue: 0,0:28:32.08,0:28:37.05,Default,,0000,0000,0000,,There's another phrase, another word\Nwe sometimes use, that's anaplastic.
Dialogue: 0,0:28:37.05,0:28:40.05,Default,,0000,0000,0000,,Anaplastic refers to
Dialogue: 0,0:28:40.05,0:28:44.05,Default,,0000,0000,0000,,well, some people say de-differentiated, but undifferentiated
Dialogue: 0,0:28:44.05,0:28:47.03,Default,,0000,0000,0000,,just immature or undifferentiated tissue
Dialogue: 0,0:28:47.03,0:28:48.42,Default,,0000,0000,0000,,we refer to
Dialogue: 0,0:28:48.42,0:28:51.01,Default,,0000,0000,0000,,as anaplastic.
Dialogue: 0,0:28:51.01,0:28:53.80,Default,,0000,0000,0000,,There's a complete range
Dialogue: 0,0:28:53.80,0:28:56.10,Default,,0000,0000,0000,,of possibilities.
Dialogue: 0,0:28:56.10,0:28:58.03,Default,,0000,0000,0000,,Let me illustrate
Dialogue: 0,0:28:58.03,0:29:02.31,Default,,0000,0000,0000,,this for you in two extremes
Dialogue: 0,0:29:02.31,0:29:05.02,Default,,0000,0000,0000,,Here is normal colonic
Dialogue: 0,0:29:05.02,0:29:08.07,Default,,0000,0000,0000,,mucosa, and we're going to talk about this in detail on Wednesday.
Dialogue: 0,0:29:08.07,0:29:10.77,Default,,0000,0000,0000,,The mucosa has these
Dialogue: 0,0:29:10.77,0:29:14.14,Default,,0000,0000,0000,,kind of tubular glands, that's all I want\Nyou to get out of this, this is perfectly normal
Dialogue: 0,0:29:14.14,0:29:15.01,Default,,0000,0000,0000,,
Dialogue: 0,0:29:15.01,0:29:21.06,Default,,0000,0000,0000,,The next slide will be a cancer derived\Nfrom this mucosa, looks like that.
Dialogue: 0,0:29:21.06,0:29:23.04,Default,,0000,0000,0000,,Now you say, that doesn't look anything like it, but
Dialogue: 0,0:29:23.04,0:29:26.06,Default,,0000,0000,0000,,in a sense it does.
Dialogue: 0,0:29:26.06,0:29:31.05,Default,,0000,0000,0000,,it's got glands, they're kind of\Nfunky and kinky and so forth
Dialogue: 0,0:29:31.05,0:29:33.03,Default,,0000,0000,0000,,but they're clearly glands.
Dialogue: 0,0:29:33.03,0:29:36.01,Default,,0000,0000,0000,,You'll also notice that the pink to\Nblue ratio has changed, a lot of hyperchromatism
Dialogue: 0,0:29:36.01,0:29:40.03,Default,,0000,0000,0000,,a lot more nuclei here and so forth but basically
Dialogue: 0,0:29:40.03,0:29:44.06,Default,,0000,0000,0000,,a pathologist looking at this\Nwould take about a nanosecond as you will learn
Dialogue: 0,0:29:44.06,0:29:46.05,Default,,0000,0000,0000,,this spring and say oh!
Dialogue: 0,0:29:46.05,0:29:48.00,Default,,0000,0000,0000,,this is a glandular type of
Dialogue: 0,0:29:48.00,0:29:49.05,Default,,0000,0000,0000,,neoplasm.
Dialogue: 0,0:29:49.05,0:29:50.01,Default,,0000,0000,0000,,So we say
Dialogue: 0,0:29:50.01,0:29:54.03,Default,,0000,0000,0000,,this is at least moderately differentiated.
Dialogue: 0,0:29:54.03,0:29:56.07,Default,,0000,0000,0000,,Now I'll show you a step down,
Dialogue: 0,0:29:56.07,0:30:01.02,Default,,0000,0000,0000,,here's a normal bronchial mucosa, again\Ndon't worry about the details, but they're these tall
Dialogue: 0,0:30:01.02,0:30:02.49,Default,,0000,0000,0000,,columnar cells,
Dialogue: 0,0:30:02.49,0:30:04.41,Default,,0000,0000,0000,,some of them are secreting mucus
Dialogue: 0,0:30:04.41,0:30:05.01,Default,,0000,0000,0000,,others have cilia on them
Dialogue: 0,0:30:05.01,0:30:06.07,Default,,0000,0000,0000,,they're very well
Dialogue: 0,0:30:06.07,0:30:08.06,Default,,0000,0000,0000,,organized there
Dialogue: 0,0:30:08.06,0:30:11.09,Default,,0000,0000,0000,,The next line is a neoplasm derived
Dialogue: 0,0:30:11.09,0:30:15.07,Default,,0000,0000,0000,,from that cell population
Dialogue: 0,0:30:15.07,0:30:20.02,Default,,0000,0000,0000,,If someone showed me that I'd say that I\Ndon't know what that is,
Dialogue: 0,0:30:20.02,0:30:22.72,Default,,0000,0000,0000,,that is an undifferentiated, malignant
Dialogue: 0,0:30:22.72,0:30:25.04,Default,,0000,0000,0000,,neoplasm,
Dialogue: 0,0:30:25.04,0:30:27.08,Default,,0000,0000,0000,,or anaplastic neoplasm.
Dialogue: 0,0:30:27.08,0:30:29.07,Default,,0000,0000,0000,,And when
Dialogue: 0,0:30:29.07,0:30:33.00,Default,,0000,0000,0000,,you look at that, what it\Nreally says is it's a population of cells
Dialogue: 0,0:30:33.00,0:30:34.02,Default,,0000,0000,0000,,that's not maturing
Dialogue: 0,0:30:34.02,0:30:38.01,Default,,0000,0000,0000,,you can't tell what it's\Ndoing or where it came from,
Dialogue: 0,0:30:38.01,0:30:43.04,Default,,0000,0000,0000,,but it sure as the dickens looks\Nmalignant, look at those huge nuclei
Dialogue: 0,0:30:43.04,0:30:47.02,Default,,0000,0000,0000,,increased n-to-c ratio (nucleus to cytoplasm)
Dialogue: 0,0:30:47.02,0:30:50.01,Default,,0000,0000,0000,,they are actually pleomorphic, they are hyperchromatic,
Dialogue: 0,0:30:50.01,0:30:51.04,Default,,0000,0000,0000,,there are
Dialogue: 0,0:30:51.04,0:30:54.00,Default,,0000,0000,0000,,tumor giant cells there.
Dialogue: 0,0:30:54.00,0:30:57.08,Default,,0000,0000,0000,,Really, you'll learn to look at those\Nthings and loathe them, to say that is an ugly
Dialogue: 0,0:30:57.08,0:30:59.05,Default,,0000,0000,0000,,cell population
Dialogue: 0,0:30:59.05,0:31:02.03,Default,,0000,0000,0000,,so that is a highly anaplastic cell population.
Dialogue: 0,0:31:02.03,0:31:04.03,Default,,0000,0000,0000,,Now,
Dialogue: 0,0:31:04.03,0:31:06.07,Default,,0000,0000,0000,,it turns out
Dialogue: 0,0:31:06.07,0:31:07.08,Default,,0000,0000,0000,,well, let me give you
Dialogue: 0,0:31:07.08,0:31:11.07,Default,,0000,0000,0000,,a rule of thumb first.
Dialogue: 0,0:31:11.07,0:31:13.06,Default,,0000,0000,0000,,Benign neoplasms
Dialogue: 0,0:31:13.06,0:31:17.09,Default,,0000,0000,0000,,are always splendidly well\Ndifferentiated, sometimes you get in the
Dialogue: 0,0:31:17.09,0:31:21.10,Default,,0000,0000,0000,,middle of a benign neoplasm, you can't tell it from the normal tissues, so a benign
Dialogue: 0,0:31:21.10,0:31:23.09,Default,,0000,0000,0000,,neoplasms are always
Dialogue: 0,0:31:23.09,0:31:25.00,Default,,0000,0000,0000,,well-differentiated.
Dialogue: 0,0:31:25.00,0:31:29.02,Default,,0000,0000,0000,,Almost perfectly differentiated.
Dialogue: 0,0:31:29.02,0:31:32.30,Default,,0000,0000,0000,,Malignant neoplasms show the whole range,
Dialogue: 0,0:31:32.30,0:31:37.04,Default,,0000,0000,0000,,there are very well differentiated but\Nnonetheless malignant neoplasms
Dialogue: 0,0:31:37.04,0:31:38.06,Default,,0000,0000,0000,,and there are highly anaplastic
Dialogue: 0,0:31:38.06,0:31:43.05,Default,,0000,0000,0000,,like this.
Dialogue: 0,0:31:43.05,0:31:46.09,Default,,0000,0000,0000,,In some situations, in many situations,
Dialogue: 0,0:31:46.09,0:31:49.07,Default,,0000,0000,0000,,in malignant neoplasms,
Dialogue: 0,0:31:49.07,0:31:54.04,Default,,0000,0000,0000,,there is a a rough correlation, I emphasize rough,
Dialogue: 0,0:31:54.04,0:31:55.02,Default,,0000,0000,0000,,between the degree
Dialogue: 0,0:31:55.02,0:31:59.08,Default,,0000,0000,0000,,of differentiation and the\Nbehavior.
Dialogue: 0,0:31:59.08,0:32:02.80,Default,,0000,0000,0000,,This is not uniform for all neoplasms
Dialogue: 0,0:32:02.80,0:32:06.08,Default,,0000,0000,0000,,and remember well differentiated\Nneoplasms/cancers can still kill.
Dialogue: 0,0:32:06.08,0:32:07.08,Default,,0000,0000,0000,,But for
Dialogue: 0,0:32:07.08,0:32:09.06,Default,,0000,0000,0000,,some situations, it's a
Dialogue: 0,0:32:09.06,0:32:11.01,Default,,0000,0000,0000,,useful label that we
Dialogue: 0,0:32:11.01,0:32:14.10,Default,,0000,0000,0000,,give it to send to our colleagues
Dialogue: 0,0:32:14.10,0:32:16.36,Default,,0000,0000,0000,,where we say
Dialogue: 0,0:32:16.36,0:32:19.01,Default,,0000,0000,0000,,we label it
Dialogue: 0,0:32:19.01,0:32:24.56,Default,,0000,0000,0000,,depending on the degree of\Ndifferentiation we call this ''grading'',
Dialogue: 0,0:32:24.56,0:32:27.09,Default,,0000,0000,0000,,histological grading of neoplasm.
Dialogue: 0,0:32:27.09,0:32:31.02,Default,,0000,0000,0000,,The grading of neoplasms is really
Dialogue: 0,0:32:31.02,0:32:36.04,Default,,0000,0000,0000,,an assessment of the\Ndegree of differentiation of the neoplasm based on,
Dialogue: 0,0:32:36.04,0:32:38.06,Default,,0000,0000,0000,,i mean we look under the microscope,
Dialogue: 0,0:32:38.06,0:32:42.01,Default,,0000,0000,0000,,and we say oh! this looks just like
Dialogue: 0,0:32:42.01,0:32:44.53,Default,,0000,0000,0000,,such-and-such tissue that's well\Ndifferentiated
Dialogue: 0,0:32:44.53,0:32:48.08,Default,,0000,0000,0000,,we sometimes take into account in these\Ngrading systems
Dialogue: 0,0:32:48.08,0:32:51.04,Default,,0000,0000,0000,,the number of mitoses
Dialogue: 0,0:32:51.04,0:32:52.09,Default,,0000,0000,0000,,that's a little less usual
Dialogue: 0,0:32:52.09,0:32:55.33,Default,,0000,0000,0000,,but it's based basically on the degree of differentiation
Dialogue: 0,0:32:55.33,0:33:00.13,Default,,0000,0000,0000,,and we talk about grade one, usually grade one means
Dialogue: 0,0:33:00.13,0:33:04.42,Default,,0000,0000,0000,,the best differentiated grade, grade two to\Ngrade three, some grading systems are all
Dialogue: 0,0:33:04.42,0:33:06.66,Default,,0000,0000,0000,,the way through grade four.
Dialogue: 0,0:33:06.66,0:33:11.04,Default,,0000,0000,0000,,You get the idea, I mean you will get the\Ndetails, but when we label with the grade
Dialogue: 0,0:33:11.04,0:33:16.04,Default,,0000,0000,0000,,we say this is well differentiated and\Nour colleagues at the other end say, well
Dialogue: 0,0:33:16.04,0:33:21.05,Default,,0000,0000,0000,,maybe that'll behave a little better than\Nif Abrams said it was anaplastic.
Dialogue: 0,0:33:21.05,0:33:24.07,Default,,0000,0000,0000,,And Illl show you what this amounts to\Nvisually, again don't worry about being
Dialogue: 0,0:33:24.07,0:33:26.07,Default,,0000,0000,0000,,able to pick these out.
Dialogue: 0,0:33:26.07,0:33:28.43,Default,,0000,0000,0000,,Here is a carcinoma,
Dialogue: 0,0:33:28.43,0:33:29.10,Default,,0000,0000,0000,,
Dialogue: 0,0:33:29.10,0:33:34.03,Default,,0000,0000,0000,,cancer derived from a squamous epithelium,\Nlike the epidermis of the skin
Dialogue: 0,0:33:34.03,0:33:37.03,Default,,0000,0000,0000,,and a trained pathologist, which you will\Nbe
Dialogue: 0,0:33:37.03,0:33:42.02,Default,,0000,0000,0000,,next spring, would look at this kind of\Narrangement or all this pinky cytoplasm
Dialogue: 0,0:33:42.02,0:33:44.06,Default,,0000,0000,0000,,which represents keratin and
Dialogue: 0,0:33:44.06,0:33:45.16,Default,,0000,0000,0000,,in the cells
Dialogue: 0,0:33:45.16,0:33:46.07,Default,,0000,0000,0000,,and you'd say oh easy!
Dialogue: 0,0:33:46.07,0:33:47.06,Default,,0000,0000,0000,,That's a well-differentiated
Dialogue: 0,0:33:47.06,0:33:51.04,Default,,0000,0000,0000,,squamous cell carcinoma, this might be a grade one
Dialogue: 0,0:33:51.04,0:33:52.06,Default,,0000,0000,0000,,for
Dialogue: 0,0:33:52.06,0:33:54.02,Default,,0000,0000,0000,,instance
Dialogue: 0,0:33:54.02,0:33:56.05,Default,,0000,0000,0000,,This one is might not look like much to you, but
Dialogue: 0,0:33:56.05,0:34:00.03,Default,,0000,0000,0000,,a trained pathologist would look at this and say, well,
Dialogue: 0,0:34:00.03,0:34:01.02,Default,,0000,0000,0000,,this isn't terribly
Dialogue: 0,0:34:01.02,0:34:06.15,Default,,0000,0000,0000,,well differentiated but I can\Nstill see areas where I'll bet that's coming
Dialogue: 0,0:34:06.15,0:34:11.02,Default,,0000,0000,0000,,from the squamous epithelium, so that\Nwould be maybe a grade two or moderately
Dialogue: 0,0:34:11.02,0:34:13.02,Default,,0000,0000,0000,,differentiated
Dialogue: 0,0:34:13.02,0:34:14.09,Default,,0000,0000,0000,,Here again is a completely
Dialogue: 0,0:34:14.09,0:34:18.06,Default,,0000,0000,0000,,anaplastic cell population, someone\Nshowed me that and said where is this coming from
Dialogue: 0,0:34:18.06,0:34:19.06,Default,,0000,0000,0000,,and I'd say
Dialogue: 0,0:34:19.06,0:34:21.76,Default,,0000,0000,0000,,God only knows this is cancer.
Dialogue: 0,0:34:21.76,0:34:24.30,Default,,0000,0000,0000,,When i don't know what kind,
Dialogue: 0,0:34:24.30,0:34:29.100,Default,,0000,0000,0000,,this is really an anaplastic, probably grade three to grade four cancer
Dialogue: 0,0:34:29.100,0:34:32.100,Default,,0000,0000,0000,,and again there's a rough correlation\Nbetween
Dialogue: 0,0:34:32.100,0:34:36.39,Default,,0000,0000,0000,,the degree of differentiation and how it\Nmight behave.
Dialogue: 0,0:34:36.39,0:34:37.65,Default,,0000,0000,0000,,behave
Dialogue: 0,0:34:37.65,0:34:39.21,Default,,0000,0000,0000,,Now grading,
Dialogue: 0,0:34:39.21,0:34:42.88,Default,,0000,0000,0000,,this is all microscopic, grading is\Ndifferent than staging.
Dialogue: 0,0:34:42.88,0:34:46.03,Default,,0000,0000,0000,,Please keep these two straight
Dialogue: 0,0:34:46.03,0:34:48.39,Default,,0000,0000,0000,,and read and understand, you're going to deal
Dialogue: 0,0:34:48.39,0:34:50.59,Default,,0000,0000,0000,,with these two concepts all your lives.
Dialogue: 0,0:34:50.59,0:34:54.12,Default,,0000,0000,0000,,Staging a neoplasm is very important
Dialogue: 0,0:34:54.12,0:34:57.57,Default,,0000,0000,0000,,because of the stage that we assigned to\Na neoplasm tells the observer
Dialogue: 0,0:34:57.57,0:34:59.94,Default,,0000,0000,0000,,
Dialogue: 0,0:34:59.94,0:35:05.25,Default,,0000,0000,0000,,how far along in its natural history\Nthat neoplasm is, in other words,
Dialogue: 0,0:35:05.25,0:35:09.83,Default,,0000,0000,0000,,how big is it at the primary, how much\Ntissue has it penetrated,
Dialogue: 0,0:35:09.83,0:35:12.00,Default,,0000,0000,0000,,has it advanced to the point where it's spread
Dialogue: 0,0:35:12.00,0:35:14.02,Default,,0000,0000,0000,,elsewhere in the body.
Dialogue: 0,0:35:14.02,0:35:18.05,Default,,0000,0000,0000,,That is staging.
Dialogue: 0,0:35:18.05,0:35:23.74,Default,,0000,0000,0000,,It's based on first of all the size and\Nthe extent of the primary,
Dialogue: 0,0:35:23.74,0:35:29.71,Default,,0000,0000,0000,,the presence or absence of regional\Nlymph node metastases, and
Dialogue: 0,0:35:29.71,0:35:32.94,Default,,0000,0000,0000,,the presence or absence of distant metastases.
Dialogue: 0,0:35:32.94,0:35:36.66,Default,,0000,0000,0000,,This is sometimes referred to as the TNM system, T for tumor,
Dialogue: 0,0:35:36.66,0:35:37.07,Default,,0000,0000,0000,,
Dialogue: 0,0:35:37.07,0:35:39.60,Default,,0000,0000,0000,,what's he doing with the primary,
Dialogue: 0,0:35:39.60,0:35:41.71,Default,,0000,0000,0000,,N for regional nodes,
Dialogue: 0,0:35:41.71,0:35:43.74,Default,,0000,0000,0000,,M for distant metastases.
Dialogue: 0,0:35:43.74,0:35:45.00,Default,,0000,0000,0000,,Every organ has
Dialogue: 0,0:35:45.00,0:35:49.58,Default,,0000,0000,0000,,a slightly different staging scheme, but\Nthey're all based on this
Dialogue: 0,0:35:49.58,0:35:51.01,Default,,0000,0000,0000,,and what it gives you,
Dialogue: 0,0:35:51.01,0:35:52.91,Default,,0000,0000,0000,,if it's a low stage
Dialogue: 0,0:35:52.91,0:35:56.04,Default,,0000,0000,0000,,or a favorable stage, that says this\Ntumor hasn't advanced
Dialogue: 0,0:35:56.04,0:35:58.48,Default,,0000,0000,0000,,as far, maybe it's restricted just to
Dialogue: 0,0:35:58.48,0:36:01.03,Default,,0000,0000,0000,,the organ, the lymph nodes are negative,
Dialogue: 0,0:36:01.03,0:36:04.27,Default,,0000,0000,0000,,and there are no distant metastases,
Dialogue: 0,0:36:04.27,0:36:07.70,Default,,0000,0000,0000,,or it may be that it's penetrated quite\Na way through
Dialogue: 0,0:36:07.70,0:36:10.04,Default,,0000,0000,0000,,whatever organ it's started in, and there are already
Dialogue: 0,0:36:10.04,0:36:15.47,Default,,0000,0000,0000,,lymph node mets but we don't know of distant mets
Dialogue: 0,0:36:15.47,0:36:19.02,Default,,0000,0000,0000,,that's quite a different situation which may\Ntake a different therapeutic approach
Dialogue: 0,0:36:19.02,0:36:22.07,Default,,0000,0000,0000,,and finally if they're already distant mets, that's a very different thing.
Dialogue: 0,0:36:22.07,0:36:23.69,Default,,0000,0000,0000,,
Dialogue: 0,0:36:23.69,0:36:25.97,Default,,0000,0000,0000,,So staging
Dialogue: 0,0:36:25.97,0:36:28.30,Default,,0000,0000,0000,,gives you a very important handle on how far
Dialogue: 0,0:36:28.30,0:36:30.00,Default,,0000,0000,0000,,along the neoplasm is in the
Dialogue: 0,0:36:30.00,0:36:32.03,Default,,0000,0000,0000,,particular patient and
Dialogue: 0,0:36:32.03,0:36:34.42,Default,,0000,0000,0000,,what you should do\Ntherapeutically
Dialogue: 0,0:36:34.42,0:36:38.40,Default,,0000,0000,0000,,because of that.
Dialogue: 0,0:36:38.40,0:36:39.96,Default,,0000,0000,0000,,
Dialogue: 0,0:36:39.96,0:36:43.91,Default,,0000,0000,0000,,Now's not the time to dwell on how we\Ntell benign from malignant and
Dialogue: 0,0:36:43.91,0:36:47.97,Default,,0000,0000,0000,,in our daily work you will again get an\Nappreciation for this next
Dialogue: 0,0:36:47.97,0:36:49.58,Default,,0000,0000,0000,,spring, but suffice it to say
Dialogue: 0,0:36:49.58,0:36:53.61,Default,,0000,0000,0000,,that we pathologists can look at a tumor
Dialogue: 0,0:36:53.61,0:36:54.50,Default,,0000,0000,0000,,and make
Dialogue: 0,0:36:54.50,0:36:58.28,Default,,0000,0000,0000,,some pretty good predictions\Nabout how it may behave.
Dialogue: 0,0:36:58.28,0:37:02.32,Default,,0000,0000,0000,,In other words, if we look at a\Ntumor and it looks very well-differentiated
Dialogue: 0,0:37:02.32,0:37:05.17,Default,,0000,0000,0000,,and completely circumscribed and so on and so forth, we
Dialogue: 0,0:37:05.17,0:37:07.41,Default,,0000,0000,0000,,say it's benign
Dialogue: 0,0:37:07.41,0:37:11.100,Default,,0000,0000,0000,,and what that says is if you get the\Nwhole thing out, patient is home free.
Dialogue: 0,0:37:11.100,0:37:17.05,Default,,0000,0000,0000,,If it's invasive anaplastic, it's a very different situation.
Dialogue: 0,0:37:17.05,0:37:20.68,Default,,0000,0000,0000,,I can tell you that that the cornerstone
Dialogue: 0,0:37:20.68,0:37:22.46,Default,,0000,0000,0000,,of clinical diagnosis
Dialogue: 0,0:37:22.46,0:37:25.73,Default,,0000,0000,0000,,in the field of oncology is
Dialogue: 0,0:37:25.73,0:37:27.69,Default,,0000,0000,0000,,getting something under glass,
Dialogue: 0,0:37:27.69,0:37:29.93,Default,,0000,0000,0000,,getting in the microscope.
Dialogue: 0,0:37:29.93,0:37:31.98,Default,,0000,0000,0000,,Very few instances where
Dialogue: 0,0:37:31.98,0:37:32.76,Default,,0000,0000,0000,,
Dialogue: 0,0:37:32.76,0:37:34.75,Default,,0000,0000,0000,,
Dialogue: 0,0:37:34.75,0:37:37.04,Default,,0000,0000,0000,,therapy will be undertaken without\Nconfirmation
Dialogue: 0,0:37:37.04,0:37:41.08,Default,,0000,0000,0000,,of the fact that under the microscope that it is\Nsuch-and-such a cancer and such and such grade and so forth.
Dialogue: 0,0:37:41.08,0:37:44.00,Default,,0000,0000,0000,,so it means we need a piece of the tissue
Dialogue: 0,0:37:44.00,0:37:46.78,Default,,0000,0000,0000,,
Dialogue: 0,0:37:46.78,0:37:47.01,Default,,0000,0000,0000,,or at least
Dialogue: 0,0:37:47.01,0:37:49.07,Default,,0000,0000,0000,,some cells from the tissue
Dialogue: 0,0:37:49.07,0:37:50.91,Default,,0000,0000,0000,,to get under the microscope.
Dialogue: 0,0:37:50.91,0:37:53.59,Default,,0000,0000,0000,,
Dialogue: 0,0:37:53.59,0:37:55.09,Default,,0000,0000,0000,,What we rely on there
Dialogue: 0,0:37:55.09,0:37:59.07,Default,,0000,0000,0000,,as you might surmise from what you've\Nseen is first of all
Dialogue: 0,0:37:59.07,0:38:01.86,Default,,0000,0000,0000,,
Dialogue: 0,0:38:01.86,0:38:06.74,Default,,0000,0000,0000,,the cytologic features, how anaplastic looking are the cells, how bad is the
Dialogue: 0,0:38:06.74,0:38:12.34,Default,,0000,0000,0000,,the pleomorphism, the hyperchromatism, etc, we rely on that
Dialogue: 0,0:38:12.34,0:38:16.54,Default,,0000,0000,0000,,we rely on the relation of the cells to\None another, the loss of polarity in the system
Dialogue: 0,0:38:16.54,0:38:18.87,Default,,0000,0000,0000,,and so forth, and
Dialogue: 0,0:38:18.87,0:38:24.53,Default,,0000,0000,0000,,we rely on the relation of the\Ntumor to its surroundings, the nice pushing
Dialogue: 0,0:38:24.53,0:38:28.28,Default,,0000,0000,0000,,margin vs boy! there goes\Ninvasion
Dialogue: 0,0:38:28.28,0:38:32.53,Default,,0000,0000,0000,,it's that sort of thing. Now
Dialogue: 0,0:38:32.53,0:38:33.84,Default,,0000,0000,0000,,I'll give you just a
Dialogue: 0,0:38:33.84,0:38:36.06,Default,,0000,0000,0000,,very quick example of that.
Dialogue: 0,0:38:36.06,0:38:37.10,Default,,0000,0000,0000,,Here is a
Dialogue: 0,0:38:37.10,0:38:40.01,Default,,0000,0000,0000,,you can imagine that colon I showed you
Dialogue: 0,0:38:40.01,0:38:41.14,Default,,0000,0000,0000,,in the cut,
Dialogue: 0,0:38:41.14,0:38:44.08,Default,,0000,0000,0000,,here is a mucosa, a submucosa, here is a muscular wall,
Dialogue: 0,0:38:44.08,0:38:46.02,Default,,0000,0000,0000,,here's the tumor arising in the mucosa.
Dialogue: 0,0:38:46.02,0:38:48.48,Default,,0000,0000,0000,,
Dialogue: 0,0:38:48.48,0:38:52.78,Default,,0000,0000,0000,,You see under the microscope here, you can see kind of glandular spaces there.
Dialogue: 0,0:38:52.78,0:38:53.10,Default,,0000,0000,0000,,Look what's happening,
Dialogue: 0,0:38:53.10,0:38:55.60,Default,,0000,0000,0000,,you've got glands
Dialogue: 0,0:38:55.60,0:38:58.78,Default,,0000,0000,0000,,penetrating clear down through the muscle there.
Dialogue: 0,0:38:58.78,0:39:00.80,Default,,0000,0000,0000,,
Dialogue: 0,0:39:00.80,0:39:02.00,Default,,0000,0000,0000,,That's a no brainer
Dialogue: 0,0:39:02.00,0:39:07.33,Default,,0000,0000,0000,,when we see something like that we say it's\Ninvading, it's malignant.
Dialogue: 0,0:39:07.33,0:39:10.86,Default,,0000,0000,0000,,That make sense?
Dialogue: 0,0:39:10.86,0:39:15.20,Default,,0000,0000,0000,,Sometimes we don't rely entirely on\Nthat, we rely on other things
Dialogue: 0,0:39:15.20,0:39:17.03,Default,,0000,0000,0000,,The cytology, just quickly,
Dialogue: 0,0:39:17.03,0:39:20.72,Default,,0000,0000,0000,,there are normal colonic epithelial cells
Dialogue: 0,0:39:20.72,0:39:23.77,Default,,0000,0000,0000,,I'm not going to describe it, just let the pictures speak for themselves.
Dialogue: 0,0:39:23.77,0:39:26.57,Default,,0000,0000,0000,,You'll catch up with this in\Nthe spring.
Dialogue: 0,0:39:26.57,0:39:32.36,Default,,0000,0000,0000,,Here are neoplastic epithelial cells. Again, normal...neoplastic.
Dialogue: 0,0:39:32.36,0:39:34.100,Default,,0000,0000,0000,,Here's a normal squamous
Dialogue: 0,0:39:34.100,0:39:39.79,Default,,0000,0000,0000,,epithelium, we're back to cervix, here's normal squamous
Dialogue: 0,0:39:39.79,0:39:41.59,Default,,0000,0000,0000,,
Dialogue: 0,0:39:41.59,0:39:43.48,Default,,0000,0000,0000,,here's dysplastic.
Dialogue: 0,0:39:43.48,0:39:50.20,Default,,0000,0000,0000,,you saw that before, this variation, this loss of polarity, the individual features
Dialogue: 0,0:39:50.20,0:39:52.04,Default,,0000,0000,0000,,of cytology here, that's a
Dialogue: 0,0:39:52.04,0:39:56.08,Default,,0000,0000,0000,,degree of dysplasia, it's a step towards cancer.
Dialogue: 0,0:39:56.08,0:40:01.04,Default,,0000,0000,0000,,This one we said was full thickness 'awfulness' with very anaplastic cells, I won't go into the details again.
Dialogue: 0,0:40:01.04,0:40:02.32,Default,,0000,0000,0000,,
Dialogue: 0,0:40:02.32,0:40:04.36,Default,,0000,0000,0000,,The concept is important, when dysplasia gets severe
Dialogue: 0,0:40:04.36,0:40:07.24,Default,,0000,0000,0000,,it's tantamount to
Dialogue: 0,0:40:07.24,0:40:11.44,Default,,0000,0000,0000,,cancer in situ, whether or not it's invaded,
Dialogue: 0,0:40:11.44,0:40:14.71,Default,,0000,0000,0000,,you see in the colonic example, we showed you invasion.
Dialogue: 0,0:40:14.71,0:40:18.05,Default,,0000,0000,0000,,Here we can say this epithelium is cancerous, dammit!
Dialogue: 0,0:40:18.05,0:40:21.99,Default,,0000,0000,0000,,Whether it invaded or not, we got to get it out or\Nsomething bad is going to happen because
Dialogue: 0,0:40:21.99,0:40:26.10,Default,,0000,0000,0000,,virtually 100% of these severe dysplasias will invade.
Dialogue: 0,0:40:26.10,0:40:26.06,Default,,0000,0000,0000,,And that is
Dialogue: 0,0:40:26.06,0:40:27.09,Default,,0000,0000,0000,,carcinoma in situ.
Dialogue: 0,0:40:27.09,0:40:29.48,Default,,0000,0000,0000,,
Dialogue: 0,0:40:29.48,0:40:32.01,Default,,0000,0000,0000,,You'll hear a lot more about that
Dialogue: 0,0:40:32.01,0:40:35.51,Default,,0000,0000,0000,,Now
Dialogue: 0,0:40:35.51,0:40:38.50,Default,,0000,0000,0000,,
Dialogue: 0,0:40:38.50,0:40:41.29,Default,,0000,0000,0000,,clearly if you look at something like\Nthis
Dialogue: 0,0:40:41.29,0:40:46.72,Default,,0000,0000,0000,,you realize that that individual cells\Nin that population bear the
Dialogue: 0,0:40:46.72,0:40:48.28,Default,,0000,0000,0000,,imprint
Dialogue: 0,0:40:48.28,0:40:51.18,Default,,0000,0000,0000,,of their malignancy, in other words, they\Nhave these anaplastic traits and you
Dialogue: 0,0:40:51.18,0:40:53.16,Default,,0000,0000,0000,,can say these are malignant cells.
Dialogue: 0,0:40:53.16,0:40:56.35,Default,,0000,0000,0000,,A guy named the george papanicolaou
Dialogue: 0,0:40:56.35,0:40:58.85,Default,,0000,0000,0000,,over half a century ago
Dialogue: 0,0:40:58.85,0:41:02.09,Default,,0000,0000,0000,,realized that that this was a great\Nhandle, that if you
Dialogue: 0,0:41:02.09,0:41:08.32,Default,,0000,0000,0000,,took cells that exfoliated, that is\Ndropped off the surface, of
Dialogue: 0,0:41:08.32,0:41:09.87,Default,,0000,0000,0000,,a place where there might be a tumor
Dialogue: 0,0:41:09.87,0:41:12.01,Default,,0000,0000,0000,,that these exfoliated cells
Dialogue: 0,0:41:12.01,0:41:13.67,Default,,0000,0000,0000,,would bear
Dialogue: 0,0:41:13.67,0:41:17.07,Default,,0000,0000,0000,,some of these traits, these anaplastic traits, and all you'd have to do
Dialogue: 0,0:41:17.07,0:41:20.04,Default,,0000,0000,0000,,is look at these cells and say WOW
Dialogue: 0,0:41:20.04,0:41:22.06,Default,,0000,0000,0000,,this is so and so.
Dialogue: 0,0:41:22.06,0:41:27.53,Default,,0000,0000,0000,,This is, as I'm sure you're aware, the origin of\Nthe so-called Pap smear,
Dialogue: 0,0:41:27.53,0:41:29.10,Default,,0000,0000,0000,,and the beauty of the Pap smear is that you don't have to
Dialogue: 0,0:41:29.10,0:41:32.88,Default,,0000,0000,0000,,cut out a piece of tissue from the person.
Dialogue: 0,0:41:32.88,0:41:33.10,Default,,0000,0000,0000,,
Dialogue: 0,0:41:33.10,0:41:35.09,Default,,0000,0000,0000,,All you need is a sample
Dialogue: 0,0:41:35.09,0:41:37.01,Default,,0000,0000,0000,,of the usually it's mucus
Dialogue: 0,0:41:37.01,0:41:38.02,Default,,0000,0000,0000,,
Dialogue: 0,0:41:38.02,0:41:40.19,Default,,0000,0000,0000,,
Dialogue: 0,0:41:40.19,0:41:41.06,Default,,0000,0000,0000,,over the area, now
Dialogue: 0,0:41:41.06,0:41:45.04,Default,,0000,0000,0000,,this has been perfected, this has changed the whole face of
Dialogue: 0,0:41:45.04,0:41:49.74,Default,,0000,0000,0000,,how we deal with cervix cancer
Dialogue: 0,0:41:49.74,0:41:53.61,Default,,0000,0000,0000,,but you can imagine a cervix...no let's back up,
Dialogue: 0,0:41:53.61,0:41:55.46,Default,,0000,0000,0000,,
Dialogue: 0,0:41:55.46,0:41:57.57,Default,,0000,0000,0000,,looking like that
Dialogue: 0,0:41:57.57,0:41:58.72,Default,,0000,0000,0000,,and that are
Dialogue: 0,0:41:58.72,0:42:02.32,Default,,0000,0000,0000,,exfoliated, remember they come\Noff here and getting a Pap smear
Dialogue: 0,0:42:02.32,0:42:04.07,Default,,0000,0000,0000,,involves getting a little bit of mucus
Dialogue: 0,0:42:04.07,0:42:08.98,Default,,0000,0000,0000,,scraped off the surface of the middle of\Nsome of these cells and
Dialogue: 0,0:42:08.98,0:42:10.81,Default,,0000,0000,0000,,from a normal epithelium like this
Dialogue: 0,0:42:10.81,0:42:14.01,Default,,0000,0000,0000,,you're going to see
Dialogue: 0,0:42:14.01,0:42:17.01,Default,,0000,0000,0000,,and i'll show you a Pap smear
Dialogue: 0,0:42:17.01,0:42:19.19,Default,,0000,0000,0000,,whereas from this
Dialogue: 0,0:42:19.19,0:42:20.31,Default,,0000,0000,0000,,
Dialogue: 0,0:42:20.31,0:42:23.92,Default,,0000,0000,0000,,or this, you're going to get a\Ndifferent kind of cell exfoliating out
Dialogue: 0,0:42:23.92,0:42:24.08,Default,,0000,0000,0000,,
Dialogue: 0,0:42:24.08,0:42:29.06,Default,,0000,0000,0000,,and without really having to get a big piece\Nof tissue, you get a little bit a swatch of
Dialogue: 0,0:42:29.06,0:42:32.71,Default,,0000,0000,0000,,mucus you can tell what you're dealing\Nwith.
Dialogue: 0,0:42:32.71,0:42:34.71,Default,,0000,0000,0000,,I'll let you see this for yourselves.
Dialogue: 0,0:42:34.71,0:42:36.11,Default,,0000,0000,0000,,
Dialogue: 0,0:42:36.11,0:42:40.50,Default,,0000,0000,0000,,Well, here are just some of\Ncellular features of anaplasia.
Dialogue: 0,0:42:40.50,0:42:44.08,Default,,0000,0000,0000,,Any look at a cell population like\Nthis with the huge nuclei
Dialogue: 0,0:42:44.08,0:42:47.22,Default,,0000,0000,0000,,there's a tripolar division figure there,
Dialogue: 0,0:42:47.22,0:42:52.01,Default,,0000,0000,0000,,those are the kinds of features we\Nlook for, all right here is a normal Pap smear.
Dialogue: 0,0:42:52.01,0:42:54.64,Default,,0000,0000,0000,,
Dialogue: 0,0:42:54.64,0:42:58.45,Default,,0000,0000,0000,,You look at that without any training at\Nall and you say well those cells look like one another
Dialogue: 0,0:42:58.45,0:42:59.82,Default,,0000,0000,0000,,
Dialogue: 0,0:42:59.82,0:43:02.01,Default,,0000,0000,0000,,look like they're all out of the same\Ncookie cutter, same N-C ratio
Dialogue: 0,0:43:02.01,0:43:07.09,Default,,0000,0000,0000,,the nuclei are not pleomorphic, they are not very regular
Dialogue: 0,0:43:07.09,0:43:08.70,Default,,0000,0000,0000,,etcetera etcetera etcetera
Dialogue: 0,0:43:08.70,0:43:11.22,Default,,0000,0000,0000,,Normal pap smear next case,
Dialogue: 0,0:43:11.22,0:43:14.59,Default,,0000,0000,0000,,now suppose that epithelium looked like
Dialogue: 0,0:43:14.59,0:43:19.04,Default,,0000,0000,0000,,the bad one I showed you, there you are,
Dialogue: 0,0:43:19.04,0:43:20.83,Default,,0000,0000,0000,,I'm showing you the extremes,
Dialogue: 0,0:43:20.83,0:43:22.02,Default,,0000,0000,0000,,
Dialogue: 0,0:43:22.02,0:43:25.09,Default,,0000,0000,0000,,instead of being very regular, these are\Nextremely pleomorphic cells with increased N-C ratio
Dialogue: 0,0:43:25.09,0:43:28.00,Default,,0000,0000,0000,,hyperchromatism
Dialogue: 0,0:43:28.00,0:43:31.10,Default,,0000,0000,0000,,and so forth,
Dialogue: 0,0:43:31.10,0:43:35.89,Default,,0000,0000,0000,,the cytopathologist looking at this doesn't have to pause very often and say
Dialogue: 0,0:43:35.89,0:43:37.08,Default,,0000,0000,0000,,this
Dialogue: 0,0:43:37.08,0:43:40.45,Default,,0000,0000,0000,,has been exfoliated from a malignant cell\Npopulation
Dialogue: 0,0:43:40.45,0:43:41.84,Default,,0000,0000,0000,,and the nice thing is
Dialogue: 0,0:43:41.84,0:43:44.48,Default,,0000,0000,0000,,that in between the cytopathologist can also
Dialogue: 0,0:43:44.48,0:43:48.45,Default,,0000,0000,0000,,look at this and say well this\Nprobably came from a cervix with
Dialogue: 0,0:43:48.45,0:43:50.61,Default,,0000,0000,0000,,moderate dysplasia
Dialogue: 0,0:43:50.61,0:43:53.54,Default,,0000,0000,0000,,or minimal dysplasia or something like\Nthat,
Dialogue: 0,0:43:53.54,0:43:58.15,Default,,0000,0000,0000,,so that not only can we catch cancers\Nwhen they're perhaps too small to appreciate
Dialogue: 0,0:43:58.15,0:43:59.66,Default,,0000,0000,0000,,by ordinary examination
Dialogue: 0,0:43:59.66,0:44:01.19,Default,,0000,0000,0000,,we can actually
Dialogue: 0,0:44:01.19,0:44:03.21,Default,,0000,0000,0000,,catch dysplastic epithelium
Dialogue: 0,0:44:03.21,0:44:07.12,Default,,0000,0000,0000,,before it's become cancer or carcinoma in situ
Dialogue: 0,0:44:07.12,0:44:11.30,Default,,0000,0000,0000,,before it's invaded, these things are all invisible pretty much
Dialogue: 0,0:44:11.30,0:44:11.100,Default,,0000,0000,0000,,
Dialogue: 0,0:44:11.100,0:44:15.05,Default,,0000,0000,0000,,and they will show up on the\Ncytological exam,
Dialogue: 0,0:44:15.05,0:44:19.35,Default,,0000,0000,0000,,so it's become a very powerful\Nscreening tool
Dialogue: 0,0:44:19.35,0:44:20.05,Default,,0000,0000,0000,,
Dialogue: 0,0:44:20.05,0:44:23.08,Default,,0000,0000,0000,,and it's changed the face of what we
Dialogue: 0,0:44:23.08,0:44:28.13,Default,,0000,0000,0000,,see in the way of cervix cancer, when i was a kid in pathology we used to see
Dialogue: 0,0:44:28.13,0:44:30.44,Default,,0000,0000,0000,,nothing but very advanced cervix cancer
Dialogue: 0,0:44:30.44,0:44:31.09,Default,,0000,0000,0000,,
Dialogue: 0,0:44:31.09,0:44:32.97,Default,,0000,0000,0000,,
Dialogue: 0,0:44:32.97,0:44:36.47,Default,,0000,0000,0000,,that were clear into the\Nrectal wall and bladder wall and so forth,
Dialogue: 0,0:44:36.47,0:44:40.60,Default,,0000,0000,0000,,i haven't seen one of those\Nthankfully in decades
Dialogue: 0,0:44:40.60,0:44:47.37,Default,,0000,0000,0000,,because of the application of the\NPap smear as screening.
Dialogue: 0,0:44:47.37,0:44:51.58,Default,,0000,0000,0000,,That's something you'll\Nhear a lot more about
Dialogue: 0,0:44:51.58,0:44:56.44,Default,,0000,0000,0000,,so going back to generalities, a definition
Dialogue: 0,0:44:56.44,0:45:00.09,Default,,0000,0000,0000,,of, or the diagnosis of neoplasm, requires getting something
Dialogue: 0,0:45:00.09,0:45:02.67,Default,,0000,0000,0000,,under the microscope.
Dialogue: 0,0:45:02.67,0:45:04.01,Default,,0000,0000,0000,,Now sometimes it's the whole
Dialogue: 0,0:45:04.01,0:45:07.08,Default,,0000,0000,0000,,tumor, patient presents with lump sum or
Dialogue: 0,0:45:07.08,0:45:12.02,Default,,0000,0000,0000,,you cut out the whole thing -- that's called an excisional, excisional biopsy,
Dialogue: 0,0:45:12.02,0:45:15.54,Default,,0000,0000,0000,,and that's very nice because if it's\Nbenign, you're done.
Dialogue: 0,0:45:15.54,0:45:18.17,Default,,0000,0000,0000,,If it's malignant,
Dialogue: 0,0:45:18.17,0:45:21.10,Default,,0000,0000,0000,,you have to do some other\Nthings very likely.
Dialogue: 0,0:45:21.10,0:45:24.21,Default,,0000,0000,0000,,Sometimes only a piece of tissue is\Nremoved, if it's a big mass
Dialogue: 0,0:45:24.21,0:45:27.46,Default,,0000,0000,0000,,you don't want to go and do a commando\Noperation until you know what you're
Dialogue: 0,0:45:27.46,0:45:28.00,Default,,0000,0000,0000,,dealing with.
Dialogue: 0,0:45:28.00,0:45:32.29,Default,,0000,0000,0000,,That may be an incisional biopsy, you take a wedge of it out.
Dialogue: 0,0:45:32.29,0:45:36.09,Default,,0000,0000,0000,,There are various biting forceps where
Dialogue: 0,0:45:36.09,0:45:37.07,Default,,0000,0000,0000,,
Dialogue: 0,0:45:37.07,0:45:39.26,Default,,0000,0000,0000,,bite a piece out
Dialogue: 0,0:45:39.26,0:45:41.51,Default,,0000,0000,0000,,and there are punch forceps
Dialogue: 0,0:45:41.51,0:45:44.98,Default,,0000,0000,0000,,particularly for skin things where you take a punch,
Dialogue: 0,0:45:44.98,0:45:46.46,Default,,0000,0000,0000,,it's a little boring,
Dialogue: 0,0:45:46.46,0:45:47.01,Default,,0000,0000,0000,,finally
Dialogue: 0,0:45:47.01,0:45:48.32,Default,,0000,0000,0000,,
Dialogue: 0,0:45:48.32,0:45:52.24,Default,,0000,0000,0000,,very often there are a variety of needles that are used where you can
Dialogue: 0,0:45:52.24,0:45:56.49,Default,,0000,0000,0000,,put a needle into a mass with very,
Dialogue: 0,0:45:56.49,0:45:58.69,Default,,0000,0000,0000,,nothing beyond local anesthesia even,
Dialogue: 0,0:45:58.69,0:46:01.06,Default,,0000,0000,0000,,put a needle in and draw out a core of cells
Dialogue: 0,0:46:01.06,0:46:02.04,Default,,0000,0000,0000,,and get those
Dialogue: 0,0:46:02.04,0:46:05.40,Default,,0000,0000,0000,,under the microscope
Dialogue: 0,0:46:05.40,0:46:07.03,Default,,0000,0000,0000,,and the extreme of this
Dialogue: 0,0:46:07.03,0:46:09.04,Default,,0000,0000,0000,,is putting in, and this can be done
Dialogue: 0,0:46:09.04,0:46:12.41,Default,,0000,0000,0000,,you know with CT guidance into\Ninternal organs
Dialogue: 0,0:46:12.41,0:46:14.93,Default,,0000,0000,0000,,put a very fine skinny needle in there
Dialogue: 0,0:46:14.93,0:46:16.97,Default,,0000,0000,0000,,suck out some juice
Dialogue: 0,0:46:16.97,0:46:18.00,Default,,0000,0000,0000,,from the
Dialogue: 0,0:46:18.00,0:46:19.52,Default,,0000,0000,0000,,lump
Dialogue: 0,0:46:19.52,0:46:22.06,Default,,0000,0000,0000,,and that juice will usually contain a few\Nfloating cells
Dialogue: 0,0:46:22.06,0:46:26.00,Default,,0000,0000,0000,,and the trained cytopathologist could\Nlook at the degree of anaplasia and so forth
Dialogue: 0,0:46:26.00,0:46:29.09,Default,,0000,0000,0000,,in those cells and make a diagnosis.
Dialogue: 0,0:46:29.09,0:46:32.04,Default,,0000,0000,0000,,So, this is
Dialogue: 0,0:46:32.04,0:46:37.08,Default,,0000,0000,0000,,always, almost always, what we do before undertaking treatment.
Dialogue: 0,0:46:37.08,0:46:38.58,Default,,0000,0000,0000,,And
Dialogue: 0,0:46:38.58,0:46:40.07,Default,,0000,0000,0000,,
Dialogue: 0,0:46:40.07,0:46:43.75,Default,,0000,0000,0000,,just to tell you, in conclusion, that\Nthis visual exam
Dialogue: 0,0:46:43.75,0:46:49.10,Default,,0000,0000,0000,,under the scope is frequently augmented by other things.
Dialogue: 0,0:46:49.10,0:46:51.86,Default,,0000,0000,0000,,Someone asked me, for instance,
Dialogue: 0,0:46:51.86,0:46:54.83,Default,,0000,0000,0000,,can you always tell, looking at a met, where it came from, if it's an unknown
Dialogue: 0,0:46:54.83,0:46:56.16,Default,,0000,0000,0000,,primary.
Dialogue: 0,0:46:56.16,0:46:59.28,Default,,0000,0000,0000,,My answer was no, unfortunately
Dialogue: 0,0:46:59.28,0:47:02.31,Default,,0000,0000,0000,,many different glandular neoplasms
Dialogue: 0,0:47:02.31,0:47:04.27,Default,,0000,0000,0000,,look the same under the microscope,
Dialogue: 0,0:47:04.27,0:47:06.20,Default,,0000,0000,0000,,
Dialogue: 0,0:47:06.20,0:47:10.50,Default,,0000,0000,0000,,so all we can say is this came from a glandular tissue. Sometimes we can use
Dialogue: 0,0:47:10.50,0:47:13.10,Default,,0000,0000,0000,,immuno histochemical techniques,
Dialogue: 0,0:47:13.10,0:47:18.21,Default,,0000,0000,0000,,in other words, there maybe certain\Nproteins on the surface of certain cells
Dialogue: 0,0:47:18.21,0:47:21.54,Default,,0000,0000,0000,,that identify them
Dialogue: 0,0:47:21.54,0:47:26.59,Default,,0000,0000,0000,,we have a library of of antibodies\Ndirected against these various proteins
Dialogue: 0,0:47:26.59,0:47:29.71,Default,,0000,0000,0000,,and they're labeled in a certain way and\Nwe can
Dialogue: 0,0:47:29.71,0:47:35.02,Default,,0000,0000,0000,,make a cut of the tissue we have and put this on and if it lights up
Dialogue: 0,0:47:35.02,0:47:37.34,Default,,0000,0000,0000,,we know that protein is represented, and to
Dialogue: 0,0:47:37.34,0:47:41.60,Default,,0000,0000,0000,,give you a concrete example, suppose we had a lymph node that had a glandular cancer
Dialogue: 0,0:47:41.60,0:47:43.27,Default,,0000,0000,0000,,and one of the possibilities
Dialogue: 0,0:47:43.27,0:47:47.49,Default,,0000,0000,0000,,would be from the prostate
Dialogue: 0,0:47:47.49,0:47:52.23,Default,,0000,0000,0000,,we could take an antibiotic to PSA (prostate specific antigen)
Dialogue: 0,0:47:52.23,0:47:54.04,Default,,0000,0000,0000,,stain that tissue, and if it lit up,
Dialogue: 0,0:47:54.04,0:47:57.15,Default,,0000,0000,0000,,those cancer cells had the prostate antigen, easy!
Dialogue: 0,0:47:57.15,0:47:58.60,Default,,0000,0000,0000,,this came from prostate.
Dialogue: 0,0:47:58.60,0:48:01.07,Default,,0000,0000,0000,,So we use those sorts of things
Dialogue: 0,0:48:01.07,0:48:08.12,Default,,0000,0000,0000,,we've gotten into molecular methods of identifying this or that molecule and
Dialogue: 0,0:48:08.12,0:48:12.04,Default,,0000,0000,0000,,in the cell population that augments\Nwhat we can do visually and the ultimate
Dialogue: 0,0:48:12.04,0:48:13.58,Default,,0000,0000,0000,,
Dialogue: 0,0:48:13.58,0:48:18.35,Default,,0000,0000,0000,,is something you're going to hear\Na lot more about and that is subjecting
Dialogue: 0,0:48:18.35,0:48:23.09,Default,,0000,0000,0000,,the tumor to analysis with what we call\Nmicroarrays which are the system
Dialogue: 0,0:48:23.09,0:48:28.77,Default,,0000,0000,0000,,whereby you can screen for\Nthousands of genes and see which ones
Dialogue: 0,0:48:28.77,0:48:30.16,Default,,0000,0000,0000,,are activated
Dialogue: 0,0:48:30.16,0:48:32.48,Default,,0000,0000,0000,,and we're beginning to
Dialogue: 0,0:48:32.48,0:48:33.71,Default,,0000,0000,0000,,''beginning''
Dialogue: 0,0:48:33.71,0:48:38.95,Default,,0000,0000,0000,,to be able to say well with this, this,\Nthis, these genes activated
Dialogue: 0,0:48:38.95,0:48:42.56,Default,,0000,0000,0000,,this neoplasm is more likely to do this, and with\Nthis, this, this set of genes
Dialogue: 0,0:48:42.56,0:48:48.99,Default,,0000,0000,0000,,activated it's more likely to do that. That's where it is all going.
Dialogue: 0,0:48:48.99,9:59:59.99,Default,,0000,0000,0000,,Okay we'll continue this on Wednesday\Nand feed you the rest.