Imaging the Postmenopausal Ovary - HD

Introduction

Good morning everybody,

and thank you for coming to this lecture.

And thank you Bev, for inviting me to do this.

And last summer when I got the email inviting me to do this, I responded, yeah, sure, great, I'll do it.

And then I thought to myself, how am I gonna make this interesting?

And what am I gonna show everybody that they haven't seen already or that they don't know about?

And Joe, everybody who was here for the last lecture has seen everything you need to see probably, but just, I always like to survey the audience before he start.

How many people have ever seen a cyst in an ovary? Come on.

All right. How many people have seen a mural nodule?

And how many people have seen a septation? All right, good.

I'm done. That's all there is to it.

All right, so then I thought, I've always had the philosophy that if you don't think something is interesting, you probably don't know enough about it.

And I started reading and learning some stuff about it, and then I realized I really didn't know a whole lot about this, compared to what's really out there.

So I promise you a lecture like nothing you've really seen before.

And we're gonna go over some interesting stuff here.

And what I'm gonna do is, we're gonna talk about ovarian development.

We're gonna talk about the physiology of the ovary, both, premenopausal and postmenopausal.

We're gonna talk about what happens, during menopause that makes things change.

And yeah, we'll talk about some ultrasound stuff, fluid, ovarian enlargement, cyst masses.

I guess you can, you can't really give a talk about a ultrasound of the ovary without at least talking about this.

But we're really gonna look at the literature and some of the pitfalls and problems with doing this.

And then of course, the real subject here is a screening for ovarian cancer.

And I discovered I didn't really know a whole lot about this, and I'm hoping that when you're done, when I'm done with this lecture, you'll know, something about this as well and be able to put all this into context.

Developmental Biology of the Ovary

So we're gonna talk about developmental biology, alright?

And you're probably wondering to yourself, why would somebody who's talking about postmenopausal ovary start by talking about the developmental biology of the ovary in a fetus?

Okay? Anybody have any idea why?

I promise you, I'm gonna tell you. Okay.

I know we hear this a lot on TV lately, that you're gonna hear things, but, I promise you I'm gonna talk to you about this.

So, first of all, all of us basically start off as a three layer embryo, okay?

And if you remember this from your developmental biology days, we are derm, mesoderm, and endoderm.

And what developmental biology, what we are good at is making tubes.

Alright? So we make concentric tubes.

Your neuro, your CNS is a tube.

The cardiovascular system is a tube.

The gi tract is a tube, but there is an exception to this, okay?

And the only cells in the body that aren't formed from these three cellular turn out to be gametes, okay?

Gametes and peritoneal lining. Okay?

And so when we're a little embryo, we're all little chickens, you know?

And we have a yolk sack.

And here's the yolk sack here, connecting inside the body of the embryo.

Here's endoderm, mesoderm ectoderm, okay?

Cells develop inside the yolk sac that actually migrate up into the peritoneal cavity, of the embryo.

And along with this, the lining of the yolk sac enters as well and actually develops along the inside of the GI tract.

And this is gonna be the future peritoneum, okay?

And you can see, various stages, of development here.

But the real exception here are spermatozoa and oocytes.

And they form from different cell line than everything else.

Okay? Well, why do we care about that?

Well, I'm gonna tell you why we care about that eventually.

So here we go. We have these little cells that are gonna be gametes, alright?

They're moving up from the yolk sack, they're moving into the peritoneal cavity, and they settle, okay?

And these urogenital grooves is what this is called here, okay?

And on this schematic, this is aorta here, this is the kidneys.

This is a little glomerular here, and some tubules.

So this is gonna be the kidney in cross-section.

This is gonna be the gu track.

This is gonna be the gi tract, the aorta.

And here we are developing, our ovary, or testes these right here.

And these cells that are gonna be the gametes, work their way up from the yolk sac and into the peritoneal cavity.

And of course, early on, the development of the ovary or the testicle is very similar, okay?

And the difference that occurs is really the plumbing, the tubing that connects, these organs to the rest of the body.

And we know that the wolf and duct is ultimately gonna end up forming the vast deference and the malaria and ductal, regress.

Whereas in a, in a woman, the wolf and duct regresses and the malaria ducts are gonna ultimately form uterus, and cervix and vagina.

Now, one big difference between ovary and testes is that the testic is much more vascularized, actually.

The butt supply to the ovary is much less prominent, actually, than in an ovary.

Okay? So we start off, okay, this is what an ovary looks like to begin with, we're on the urogenital groove here, and we have a lining of epithelium, okay?

And then we have this basement membrane, and then we have the stroma.

Okay? And this is really important ultimately, because this thing is what starts, okay?

And then ultimately gametes, OO ovaries, oocytes, populate, this structure and they form and this becomes more organized.

And you have oocytes, you have stroma, and then you have the basement membrane.

Okay? And so these are really the three cell types that are in the ovary.

And these are the three types of cancers we're really gonna talk about later towards the end of the discussion.

But it's important to recognize that the ovary is a little unique in that this part of the ovary actually projects into the peritoneum, okay?

And keep in mind that the peritoneum also developed along with these oocytes, okay?

'cause this is gonna mean something ultimately.

So you have, it's quite a bit like a tree.

And, the fruit of the tree, the oocytes is, really in the peritoneum, okay?

Whereas the stroma and the vascularity are really originating from the retroperitoneum, when they enter the ovary.

And ultimately, this is what a mature ovary, would end up looking like.

Okay? And this is important to recognize, and I'm gonna go over this later, is that this is epithelium.

This is the most common kind of ovarian cancer is epithelial.

But you can have, germ cell cancers as well, less common.

And then you can have stromal tumors as well.

And we'll come back to that in a second.

Premenopausal Ovarian Physiology

Well, all of us just heard about the premenopausal, ovary.

Terry gave a wonderful lecture.

And, we all know you have primorial follicles.

They mature, ultimately they rupture, they ovulate.

You get a corpus lium.

And then if, fertilization and a pregnancy doesn't result, they degenerate.

And these are the hormone levels that go along with this.

This is luteinizing hormone, follicular stimulating hormone, okay?

We get a peak of luteinizing hormone, and that's when ovulation occurs is right here.

And this all comes from the pituitary, and the pituitary drives this.

Alright? And then this is estrogen and progesterone.

And you notice estrogen, it has two peaks, okay?

There's the secretary phase or the proliferative phase peak rather.

And then we're at secretary phase.

And this falls a little bit, and then it peaks again, basically towards the end of secretary phase prior to menstruation, whereas progesterone, really occurs, just before ovulation.

Okay? And this is what really allows the endometrium to receive, an embryo if, one is formed.

So that's premenopausal physiology, okay?

Postmenopausal Changes and Menopause

What happens in post menopause?

On post menopause, instead of having this cyclical process, a lot of these oocytes basically begin to degenerate and they become a retic.

And we get small, basically non-functioning, oocytes here, okay?

And more and more of these start to develop, the ovary atrophies.

And then we just set up with tiny little residual, material from these oocytes, okay?

The hormone levels on the other hand, because we're not making estrogen and progesterone anymore, the pituitary gland gets quite upset about this.

There's no feedback inhibition.

And her folic, follicular stimulating hormone and luteinizing hormones, increase their levels throughout menopause.

And so menopause can be defined basically as elevated levels of these pituitary hormones and very low levels of estrogen and progesterone.

Alright, well, the reason I put this really busy looking slide in here is for a couple reasons, but one is this statement up here.

Okay? So what is menopause? Alright?

Seems reasonable to define it.

Menopause is caused by depletion of Pial Foles in the ovaries, okay?

Females have a maximum number of oocytes, at 20 weeks of gestation.

Alright? So that's a clue as to why I talked about embryology a little bit.

So the follicular pool decreases gradually throughout life until about age 52 when the pool runs out.

So when you run out of active ovary oocytes, that's when menopause occurs, okay?

Most women will produce roughly, 50,000, a hundred thousand to maybe even a million oocytes during fetal development, but only 500 of them, will ovulate.

And the remaining ones that never ovulate, that never do anything are called to oocyte burden, in these patients.

And then if you look at these charts, these are the pathways, of what occurs with these hormones.

And the only thing I wanna point out is what I said before, elevated follicular stimulating hormone way high, okay?

In postmenopausal women, increased luteinizing hormone way high in postmenopausal women is all, as well, okay?

And this is all gonna be related ultimately, to the imaging of the ovary, okay?

And so we get these thing called breakthrough cysts.

And then what happens is these immature oocytes, and here's a clue that happen to have double strand breaks, induces ovarian epithelium to form tumors.

Alright? So we're gonna get back to all this in just a second here.

Ultrasound Evaluation in Postmenopausal Women

So, the postmenopausal ultrasound exam, in many ways could be considered the hunt for ovarian cancer.

I think we all know that. We don't see most of the premenopausal stuff, like dermoids and endometriomas and things like that in postmenopausal women, right?

And so there are really four things that we really talk about and look for.

When we do the postmenopausal, ovarian ultrasound exam.

We look for ovarian size, okay?

These ovaries atrophy, because they don't have mature oocytes in the many more.

So usually there are less than five ccs in volume, okay?

Pretty small. Normal might be 12, during active ovulation, maybe up to 20.

We do look for cysts.

We're gonna talk about CYS as a distinction.

We talk about cystic masses, okay?

And cystic masses are masses that have mural nodules, projections, septations debris, echogenic fluid within them.

And then we're gonna talk about ascites as well.

So these are really the ultrasound findings we're looking for.

And this is really the, the, the basis for doing the ultrasound exam.

Literature Insights on Ovarian Size and Cysts

So what I did is I went through the literature, and if you go through the literature, there are 50 to a hundred articles published every year on various aspects of this subject.

And so literally, there are thousands of articles, going back over time.

And what I did is I took all the ones that were done within the last six months just to point out where we are in this.

And I want to just point out some of the issues and problems, that we keep seeing in the literature.

So here's one, 99 postmenopausal women, 42 had surgery.

And what they were looking at is what's the mean size, of the lesions, that they see when they're screening.

Okay? Five ccs is the cutoff here.

Well, what they found was that the majority of these were solid, benign tumors.

These are all stromal tumors in general, and the vast majority of 'em were benign.

And then there were two invasive carcinomas, in this series.

So I think, we know that increased ovarian size is a real marker, for malignancy.

The problem is we'd like to find them when they're small.

Okay? This is the problem, and I don't know what size cutoffs people are using when we call them normal, but the real dilemma is if normal postmenopausal ovary is five ccs, what do you do when you have a 10 cc ovary or 20 cc ovary?

And when do you become concerned about it?

And what do we do about it?

So I'm gonna just talk about cysts for a second, because cysts are a bit of a dilemma.

And so I quote to you, this is the American College of Obstructions and, gynecologists practice bulletin on the management of adnexal masses.

And this is really, in postmenopausal women.

It's in 2015, and it says, with the exception of simple cysts on transvaginal ultrasound, most pelvic masses in postmen pasal women will require surgical intervention.

Okay? So does this mean it doesn't matter what we say, if there's a mass, it's gonna be taken out ultimately.

I mean, this is what they were suggesting, in 2015.

Management Guidelines and Consensus Reports

So a group was formed, to deliver a consensus report, okay?

The first international consensus report on adnexal masses management recommendations, okay?

And, you know, in Seattle, we have a football team, the Seattle Seahawks, you know, and the defense is called the Legion of Boom.

And, if you look at the names on this consensus panel, we have Phyllis Glen here, Phyllis here, she was here at one point.

We have Phyllis, we have Beryl, we have Beverly Coleman, we have Deb, Deb Levine.

I mean, this is clearly, as, good a, a, a defense as you could possibly have representing the SRU, right?

So what did they find and what were their recommendations?

Well, they found that in the United States, we perform 9.1 surgeries, poor malignancy, that's discovered, okay?

In European countries, based on their data, it's 2.3 surgeries, poor variant cancer found in most centers around the world.

It's 5.9 surgeries, per ovarian cancer.

So we have the distinction of doing the most surgeries, per ovarian cancer found.

And I don't think that's surprising, actually, the way our system is set up.

So the panel concluded that patients would benefit not only from more conservative approach to benign adnexo masses, but for optimization of physician referral, as well.

So it seems that most of the lesions that we're gonna find are benign, okay?

Especially when they're simple cysts, and that we're doing too many surgeries per malignancy that's found.

And so we all know, that, we developed an SRU criteria, for following cysts.

And in the postmenopausal arm of this, most of these come back for follow up for anything bigger than a centimeter.

Okay? When you're premenopausal, they can be bigger.

But right now we're following every cyst that we see.

Okay, I'm missing a slide here, but that's okay.

Um, but, so that's the recommendation now, and this is what the gynecologic surgeons wanted us to do.

Now we're gonna make a distinction here between cysts and cystic masses.

Okay? So cystic mass has septations and nodules and plus or minus flow within them.

And I'll just go over, a couple of the data.

Again, this is very recent. This is 2014.

And, this was a, the performance of ultrasound as a second line test.

This screening with CA 1 25, I said we'd talk about screening and we will 741 women, 1,219 cancers.

This study was done over almost seven years.

And when we see these, ultrasound sensitivity was a hundred percent, for abnormal, morphology, 90% for abnormal volume.

And, the highest specificity and positive predictive values, were found, for these findings.

So ultrasound is very, very good at doing this. Okay?

Distinction Between Cysts and Cystic Masses

So the question becomes, why don't screening programs using ultrasound really work?

Okay? If we look at another paper, they basically, developed a scoring system.

And there have been lots and lots of scoring systems published in the literature for how to evaluate, complex adnexo masses barrel, published one.

She has a scoring system of her own, but they pretty much have the same features, cyst wall structure going from smooth, to thick wall, to papillary projections, to solid septa, thin septa thick septa solid areas within the septa, okay?

And then the volume of the tumor.

And you notice that, you have to get, start getting pretty large, before you get higher, in the score here.

So I think all of us here are very familiar with this gradient, if you will, of how suspicion a lesion is based on size and particularly based on papillary projections.

Okay? Papillary projections are more worrisome, than septations in general.

And I just throw this in here.

We all do flow in these lesions.

If a lesion has, a mural nodule in it, it doesn't really matter whether it has flow in it or not.

In a postmenopausal woman, it's gonna be taken out.

Okay? So this is the original paper.

Thomas Bourne published this 50 women and I throw this in here.

Seven out of eight had cancer, had low RI flow.

These were the kinds of things you could publish, 20 or 30 years ago.

Now, I'm gonna show you more literature, to give you the kinds of numbers, that people talk about.

Ascites in Postmenopausal Women

We're gonna talk about the presence of ascites.

Now, what I was really looking for, what I wanted to know is how much ascites needs to be present before you start worrying about the presence of an ovarian malignancy or particularly peritoneal disease.

And so this paper, from 2007, 372 patients with ascites specifically had cytological studies and their survival, was evaluated and it was very clear that ascites is associated with omental metastases and metastatic lymph nodes.

Okay? And I think we all know this, okay?

And so the question I really wanted to know was, what if I see one or two ccs of ascites in the cul-de-sac of a postmenopausal woman?

Okay? Is that suspicious? Okay.

Should that make me start looking around?

Should that make the gene oncologist, do something to this patient?

And I can tell you that I did not find a single paper that addressed that issue, okay?

And yet for me, if I do one of these exams and I see a tiny amount of ascites, it makes me worried, okay?

Possible menopausal women really shouldn't have ascites.

So whether I see an ovarian mass or not, or peritoneal disease, I'll report ascites.

And I think these women have to have increased surveillance, certainly.

Biochemical Screening for Ovarian Carcinoma

And then that brings us to, the final part of this, and that is the biochemical screening for ovarian carcinoma.

And everybody is familiar with CA 1 25.

Everybody's heard of CA 1 25, right? We use it all the time.

What are the problems with it? Okay?

The problem with it is that there's a lot of things that do it, okay?

And premenopausal women, it doesn't mean a whole lot.

Endometriosis can do it. Fibroids do it.

PID menstruation, hyperstimulation pregnancy. Okay?

And then there's a lot of non gynecologic, fat things that can elevate CA 1 25.

CA 1 25 is really a marker of epithelial cells, okay?

And so things like congestive heart failure, renal disease, liver disease, appendicitis, pneumonia, pancreatitis, all of these can elevate CA 1 25.

So the value it seems to have is it raises some suspicion in a postmenopausal woman that, a malignancy could be present.

And it's probably a better, marker to follow as the woman gets treated, than it is for really confirming that a patient has, a malignancy here.

And if you look at all these different markers, related to epithelial cells, okay?

You see ca 1 25 right here, okay?

It doesn't have great sensitivity for ovarian cancer, okay?

At least in this data, which is from 2017, by the way.

Alright? About 13%, there's others of higher sensitivity, okay?

But it does have the highest specificity, okay?

So if it's elevated, well, this is even higher actually, but, it does have high specificity.

So again, it's very useful for following tumors.

But it's not so useful, as a screening test.

They didn't know of its own. Right? Now, how many people here have heard of BRCA one and two?

Everybody's heard of this. Nobody's voted.

It's like any other election, huh? Okay.

People have heard of these, right? Okay.

How many people really know what these do? Okay?

How many people understand what it is that the genomics and proteomics that we're talking about for screening for cancer do?

Okay, well, I didn't, I'll be honest with you until I started looking at this.

So what these genes do is they code for proteins that repair double stranded DNA breaks, okay?

And I mentioned this in the very beginning, okay?

About embryogenesis here, okay?

When do double stranded DNA breaks occur?

They occur during myosis. Okay?

They occur when the oocytes are developing. Okay?

So why is it that we are screening for ovarian cancers for something that occurs during, OA oogenesis, okay?

For something that's a follicular disease, okay?

There's a little bit of a paradox there.

It's an epithelial disease, okay?

It's not really a gamete disease, ovarian cancer, alright?

And so, but what happens is, you have these double stranded breaks, okay?

And then these cells are abnormal.

And then ultimately when these cells start growing and become a cancer, all of these proteins that are supposed to be trying to repair these breaks, multiply, okay?

And they're elevated. And then this is how we're screening for ovarian cancer.

I will point out that this is, genetics, of the BRCA one and two.

And this was the original family, who had the history of breast cancer and the black, of course of the ones who were infected.

And by tracing these genes, through this family and doing, genetic studies on them, this is how the BRCA one and two genes, were developed.

So basically BRCA one and two, repair, homologous recombination repair, that means double strand breaks.

This only occurs during myosis, okay?

And this is not the only incident time where something that occurs during developmental biology leads to disease 50 years later.

The other big one is hypertension. Okay?

All of us are born with all the nephrons we're ever gonna have, when we're neonates, okay?

And if you have fewer nephrons than you're supposed to have, even when you're a little baby, that actually predicts quite accurately who's gonna get hypertension, when they're age 50.

The problem is how do you count nephrons in somebody?

It's not possible. Well, the same thing is happening here with the, the ovary and ovarian carcinoma.

Okay? And so there are four, and this is the only process that can repair double stranded breaks, the only process that's known at the moment.

And so there's four genes necessary to do this.

So this forms the basis for the genomics, that people are studying.

And then there's all these proteins that get together.

Here's our double stranded DNA break, and we have telomere maintenance and homologous enjoining and all this stuff that we don't really know about as radiologists.

But here's our double stranded break.

Here's our complex of proteins, forming a little bridge here and pulling the ends of this together.

And this is how these get repaired, okay?

And, this occurs during meiosis.

Pathogenesis of Ovarian Carcinoma

So what is the pathogenesis of ovarian carcinoma?

And this, came out blurry. Hmm.

I had actually replaced all these slides this morning, so all my new ones didn't get in here.

But anyway, this is our surface epithelium.

And just to emphasize that the formation of cysts in the postmenopausal ovary does not follow this, oocyte, ovulation pattern, okay?

It's a different process, okay?

In postmenopausal women, they don't have any active ov oocytes anymore to ovulate.

So what happens is you get these inclusion cysts of epithelium.

So there's little breaks in the surface of the, of the ovary where the epithelium, maybe has a, some kind of crater in it or some kind of ridge or irregularity.

A little bit of epithelium gets trapped within the stroma of the ovary, and then this forms a cyst, okay?

And so then the question is, how is it that an epithelial cell like this, okay, ends up forming an ovarian cancer where all of the proteomics and gen genomics that we're looking at are for gametes?

For oocytes, okay? There's no oocytes in these.

Well, the answer to this is that all those little cells that migrated out from the yolks act during development, okay?

Seed the peritoneum seed, the fallopian tubes, some of these have double stranded breaks when these cells form some of the, when these cyst form, some of these get a little inclusion of some of these cells within them.

And it's these cells that then grow on to grow into ovarian cancers, okay?

And that's the paradox.

A how is it that if you don't have any oocytes left, that we're screening for cancers, looking at oocyte type, genomics.

And what this says here is epithelial cancers of the majority of the cancers.

Terry said the same thing.

Germ cells do not form ovarian cancers in postmenopausal women.

This is younger women. And then the stromal tumors, by and large, produce hormones and manifest much earlier as well.

So that is really the genesis, if you will, for ovarian cancer.

It is actually doublet strand breaks in the oocytes that are migrating from the yolk sac, okay?

Up along the peritoneum and then forming the ovaries.

Challenges in Screening for Ovarian Cancer

So here's the problem. Here's some literature, very recent literature here.

Well, this one's from 2000, but it illustrates the problem.

14,000 women were screened.

So 46,000 screening years, we looked at volume mural projections, only 17 cancers out of this group, and three deaths.

And while every cancer and every death is too many, this isn't very many, right?

It's a pretty small volume.

And then when you look at the literature, look at the numbers of patients, these people are reporting, you know, Tom Bourne reported, you know, 50 patients with color flow, 34,000, 50,000, 48,000.

And yet, look at the number of cancers here, very small, 34, 24, 27.

Most of them were stage one and two. But here's the problem.

Some of them really were stages three and four.

So we're looking at something that doesn't happen that often, okay?

And even when we're screening for it, using chemistry, genomics, proteomics, and ultrasound, a lot of the patients that we find still have advanced disease, and maybe this is the problem, okay?

This is an older study that really illustrates the issue.

22,000 women, underwent screening only 40 were positive, okay?

Out of the 40 that were positive, only 11 cancers were found at surgery.

So there's 30 false positives.

So we really are over calling this in most of these women.

And then the real issue is the eight false negatives.

Eight women who were screened in this study went on to have ovarian cancer.

And that's the problem. And that's what I see in my own, experience, is you'll do an exam on a patient and it's totally normal.

Six months later, a year later, she comes back and has metastatic disease.

And I find that very frustrating. Okay?

And then this is more data, and you can look, in, in your syllabus at this, but it, it, it says the same thing.

Huge numbers of patients, small numbers of epithelial cancers, okay?

And, at various stages, alright?

And so this is a problem, small numbers, alright?

And yet, I mean small numbers of cancers for large numbers of women's screen.

So there's been several groups that have published, recommendations for ovarian cancer screening.

This is from the New England Journal.

And what does this one say?

Does not recommend routine screening?

Does rut recommend routine screening?

Does not recommend screening.

Does not recommend screening, okay?

This is why is because it just doesn't really work very well.

So it's not something we should really be trying. Alright?

And, yeah, I don't like getting that phone call either.

Grandma died of ovarian cancer.

Can you take a look at her ovaries?

That makes me nervous, frankly.

Future Directions: Contrast-Enhanced Imaging

Uh, so contrast, okay, this is, the big hope for the future.

And small ovarian malignancies do have greater peak enhancement and longer washout times than normal ovary.

Here's a little tumor here. Alright?

And there's been 10 independent studies, 579 ovarian tumors, and the pooled sensitivity, 91% and specificity 92%.

And of course, art Fleischer Arthur, one of these papers, and he was just telling me this morning, there's even more papers out.

So maybe contrast will help us in this situation.

Case Examples

I'm gonna show you, these are the only images I'm gonna show you, in this study.

Here's a patient I did, 50-year-old woman asymptomatic, came in for, ultrasound exam, okay?

Took these images, thought this was a cyst, and I, I thought this was reverberation artifact and maybe it is, alright.

And, but I said, come back, this is five centimeters.

You need to come back in three months and let me look at this again.

Well, she didn't come back, she never showed up again, and I'm just about to run out the time, but I'm almost done here.

So she never came back. Nine months later, she shows up.

Now she's symptomatic and she's got neural nodules within the septation.

She's got low resistance flow.

And of course, this turned out to be an ovarian cancer, and it was stage three by the time we picked it up.

So I can tell you that 25 years later, this bothers me.

It still bothers me. It's the only time I've ever seen this happen, in my own experience.

And then this is the strangest cancer I've ever seen.

This had all this strange material in it, big mass.

Nobody would mistake this in a postmenopausal woman for anything benign.

And it turned out, it was stroma ovary eye.

It actually had thyroid tissue in it.

So it's a very strange case in reality.

Conclusion

So anyway, in conclusion, I just wanna really emphasize that the event that results in ovarian cancer occurs during embryonic miosis, okay?

As odd as that may seem, that's really when it happens.

The peritoneum and the ovary are intimately related, okay?

And it explains the spread of peritoneal disease.

The ovary forms along with the peritoneum, the cells move, wind, the peritoneum.

And it's no surprise that that's where a lot of them metastasis go.

Biochemical and genetic screening stratifies risk.

And yet, it's still not really routinely recommended for screening for ovarian cancer.

We're familiar with the worrisome findings in ultrasound.

That's why I showed you all this other stuff rather than images.

We still overtreat simple cysts, okay? Really simple cysts.

The, the pathogenesis of these as inclusion of epithelium in the ovary.

It's not, ovulation.

And this just the CYS system itself.

If it doesn't have the right cells and it is not gonna form a cancer, and in my mind, be wary of fluid,

I think even small amounts of fluid are worrisome.

And maybe contrast is the, is the great hope here.

And I thank you very much for your attention.