Endometriosis Foundation of America
Medical Conference 2019
From Biomarkers to Precision Surgery
March 8-9, 2019 - Lenox Hill Hospital, NYC
Anyway, let's go back to history and recognition. We're going to talk about recognition, deep endometriosis, what the laparoscopic appearance of the 0.080-millimeter lesion is, 80 microns you can them microscopically, and look-a-like lesions. I have no current conflicts of interest. I'm going into a venture with Lumenis CO2 Lasers next month, on the chance that they and I will work out something on education and research. For those of you who want links to some of the material that's gonna be here that's the link. If you just remember danmartinmd.com that's the third link on that page, for the next week or two until we change it.
We're gonna start with William Russell, 1899 he was taking out cancer in the left ovary. He found that in the right ovary, that looked normal, but was grossly covered in adhesions. What he found in there, if you can look at those circles, the circle in the middle is endometriosis near the hilar vessels. The other circles are endometriosis in the adhesions, which he had not noticed at the time of surgery. The adhesions areas are microscopic if you cut through the ovaries the one in the middle is macroscopic, but this is unseen endometriosis that he could not see in adhesions at the time of surgery. First recorded thing I know of someone who found it histologically but didn't see it.
John Sampson found the same thing, but he was talking about adhesions, we'll show you slides in a moment, he was talking adhesions from the rectum to the cervix, so he's talking about the cul-de-sac is completely obliterated, and if you look at those pictures when somebody talks about classical endometriosis, that's classic. The entire pouch of Douglas is gone, the bowel is adherent to the back of the cervix, back of the uterus. This is all the way since 1903. If you look at the descriptions from Roy Kotansky in 1860, it's the same descriptions. Classical is deep infiltrating rectovaginal endometriosis in the area of the pouch of Douglas, not in the septum, in spite of what they say in the textbooks, it almost never gets to the normal level of the septum. It's always in the area of the cul-de-sac.
Now, I was privileged to live two hours away from Pete Hollis. So, Pete was born in 1937, born in Amory, Mississippi, a little town of 7,000, it's about two hours from Memphis, three hours from the University of Mississippi at Jackson. He becomes American College President from a rural area in 1993, but let's go back to 1985, because in '85 I'd already published my first paper on excision, and he had sent a patient to me because he'd felt a left uterus sectoral nodule. He knows it's there. He sends her to me, 'cause he knows how to do at laparotomy.
In that day and time, this was a laparotomy thing. He wants to see if I can do it at a laparoscope, so he sends her to me. I excise it, get a histologic confirmation. We're all happy. Sent it back to her, pain is still there, he exams her, nodule is still there, and we'll show you similar nodules later on, but he sends her back to me, and tells me to get this time, and tells me what to do, because he's been operating forever, he knows exactly what to do, and why I missed it, and he says, "You examined her before the excision to make sure you know where it is, when you get in you push it up with the finger, one-finger."
This was before David decides he's a one-finger examiner. Pete Hollis knew that. You push it up into the field, and I'll show you pushing one up later on, then after you've excised it, exam her again, make sure it's gone. You don't miss them if you do that. Which brings up several papers that Pete, Harry Reich, and Gordan Davis helped me produce. The middle one, they're actually acknowledged. I should have acknowledged them in all three, but the deep excisional paper in '87, the laparoscopic vaginal colpotomy in '88, we'll about that more, and the five-millimeter definition of deep in 1989, all of those came out of that research.
So, [Koninckx 00:05:02], in Belgium, recognized that if you do a menstrual exam, you pick up nodules more than if you do an untimed exam, significantly more. After that though, he realized that when he did a laparoscopy on them some of those appear to normal, even though he knew that there was a nodule there. If we look more at that ... Okay, back up. Excuse me. I got ahead a slide, or two. So, I was lucky enough in 1981 to attend lectures by Maurice Bruhat from Clermont Ferrand, and Kurt Semm's from Kiel, German.
Kurt presented at the 10th annual AAGL meeting in Phoenix, Arizona, and Maurice Bruhat presented at one of Dr. [Balina's 00:05:53] conferences in New Orleans. By this point in time, Bruhat has been doing microscopic infertility surgery since 1977, and Kurt Semm has already published excision in 1980, so excision is not new. It doesn't belong to anybody who is in this room. Excision was first started by people who are no longer alive. That laparoscopy excision and laparoscopy had been around for 100 years, but Kurt Semm in 1980 had published an article that said nodules were too large to be coagulated, and he presents in 1981 meeting his slides on why he did excision, and he was just doing partial excision then. He just wanted to get it small enough, so he could coagulate it. Presents that, and Bruhat presents his article on how to use a laser, and after that, it was off and running, 'cause I was hooked.
One of the first papers, in 1988, was similar to what Dr. Adamyan talks about in terms of her grade one, grade two, stage one, stage two lesions up at that top, where a lesion is basically retro-cervical and does not involve the bowel. So, if it's retro-cervical, and doesn't involve the bowel you can remove it laparoscopically, so right there in the retro-cervical area. Adamyan in stage one involves just the retro-cervical area with no extension toward the rectum, and stage two extends toward the rectum. Not new, this was known in the deep cul-de-sac, behind the cervix, since ... Excuse me. It's building, wait 'til it finishes building. I'll figure out what ... There we go.
Cullen in 1917 has published that, so it was nothing new about that lesion, and his drawing in 1917 you can see he already knows illustrations of retro-cervical endometriosis that doesn't involve the rectum. So, Kurt Semm in his textbook in 1984 is going to use a laparoscope, so he can safely excise them vaginally, so in our first episodes of using a laparoscope to excise these, it's being used to guide vaginal surgery, but if you look at what we did in laparoscope, this is 1986, that's the same lesion they've been looking at. It's a retro-cervical lesion that is larger as you go after it. The surface is the smallest area, so as you go deeper into it you get to see it, so that's in between the uterosacral.
As you see there, the rectum is getting up toward the uterosacral. You worry about cul-de-sac obliteration, so you do have to believe Harry. Harry, you tell me to do what right now? What do I want to do right now? Put a ...
Put your finger in the rectum.
Yeah, put your finger in the rectum, and what else? Put a sponge forcep up there, and make sure you can see.
Yep. Harry's basic rules. Get a sponge forceps in there, so you can see everything. As I said, Harry helped develop these techniques. So, we first get the excision, and then you can see the fibrotic endometriosis and the healthy fat. For those of you who aren't used to looking at fibrotic endometriosis, and healthy fat let me put a ring around it, so that's the fibrotic endometriosis, healthy fat's at the rim, and then the peritoneum. So you understand, excision for me in that point in time is CO2 laser, so these are all laser incisions.
Now, so you can tell where it is, now we go back to Harry's basic rule that force for forcep is your friend, so you put a forcep in there, the little circle in the middle, it's the widest area, that's the tip of the forceps in the vagina, and that fibrotic endometriosis is sitting right on top of it. Once you get that view, then it's fairly easy to take that endometriosis off the vagina without injuring the vagina, but until you get that view, so that you have the thing sitting up, it's hard to know where to go, and this was the same thing that happened with that lesion with Pete Hollis's patient. We didn't push it high enough up to see it. I tried to go after it instead of bringing it to me, so for those of you who aren't doing stage three, stage four rectovaginal endometriosis, for those of you who are still doing stage one, and two this is the kind of thing you need to know.
Now, here we go. This one is slightly different. The rectum is right immediately adjacent to the cervix, at the level of the uterosacral. Here is my question for the audience, those of you like Harry do not get to answer. David doesn't get to answer. Gary doesn't get to answer. You already the answer to this one. Okay, for those of you who have never had to operate on this, that is the tip of a stage four lesion, so what you see there at the top of this is that little circle at the top there, that red circle. The yellow we'll talk about in a second, but the red is all you see, and all that other stuff is behind it. Just to notice, we'll talk about this later, 'cause it comes up in another slide, that yellow highlighted area is where this either infiltrates into the cervix, or if you believe [Jacques Donnez 00:11:38], it starts in the cervix and infiltrates towards the rectum.
We'll spot you on which one of those you want to believe, but there are two different beliefs on that, but for the moment all we see is that thing at the top. Okay, for those of you who have not done this surgery, how many of you want to start, and try and get that off the bowel at point two, and how many of you want to take it off the top at point one, so let's have a vote. How many of you start at point one? Oh, David you don't get it. Don't believe David, he already knows the answer. How about point two?
And what happens if you start at point two? You get to see the longitude, and the muscle of the bowel, 'cause this is again 1985, 1986 before we knew all this stuff, so when you see ... Hmm?
What about the rectal probe?
I know. As I said, this is 1985, 1986 before you and I have ever met '85. So, when you see these lesions, where everything is plastered together, you've got to get it off the cervix first, and I really think the best idea is coming in vaginally, and get it off the vagina first. I like that idea. That worked really well the few times we tried it. Then you get to the deeper lesions. Here is one coming through the back of the vagina, and the interesting thing is of the first seven patients we did like this, five did not have rectal involvement.
Coming through the back of the vagina two had rectal involvement, and five did not, so the five did not here is one of them, whole posterior thing. That little whiteish lesion in the middle is the one we're going after, and in the dissection if you look carefully at the lower part of that plug that we're taking out you can see healthy fat, but at the top you see the fibrotic endometriosis, and you see the fibrotic endometriosis because on this one I got lucky not to cut into the back of the cervix any deeper than that. I did, you can see, I cut across the endometriosis, but I didn't take the cervix apart. Later on, I actually went after one all the way into the cervix, took the cervix off posteriorly, got into the endocervical canal, had to open her, and repair the cervix, and this doesn't make the [EMFM 00:13:53] people happy.
They don't like when the patients are missing a third of their cervix, but when you look at that histologically, you can see the same thing histologically. The vagina is on the far left, the peritoneum is on the far right, we have healthy fat at the base, but we've cut into the endometriosis at the upper cervix, on the back of the cervix, so when it goes into the cervix don't try to track it. You're not gonna get it all unless you take off the entire back of the cervix, then you worry about premature labor, prematurity, putting babies in intensive care units, all those kind of things, so trying to go after all the endometriosis in those cases we won't do.
Now. Is Dr. Vidali ... I didn't even look and see if he's here. Is he here today? Vidali? No, he's a New York doc. Anyway, does this. This is on YouTube. For those of you who haven't seen this, I think for recognition this is a nice video. This has been up for about a month. The link is down there. The link will be on the website that I told you earlier, but when I first saw that, and he's about to do this procedure, I decided I can see what he's going after. He's going after that residual ovary right there, and I'm sure that's the residual ovary. It's obvious to me it's a residual ovary.
Then all of a sudden he starts going after that. That's the residual ovary, and it's almost impossible to look at that first slide for me to know that is the whole thing until he gets it done. You can see how that whole ovary is being flapped down, so until you get behind it, and cut into healthy tissue, and start dissecting in healthy tissue planes you really don't see the ovary. He saw it. I didn't.
Teenage endometriosis, completely different thing. If you look in there, we see those little lesions, little 400 micron lesion that has glands and stroma, 200 micron lesion that has glands only, and no stroma, but what's remarkable in that picture, and we didn't know before we looked at Dr. [Roman's 00:16:03] pictures, and Roman will be here tomorrow, when he starts seeing lesions down at the 50 micron level we went back, and blew up these pictures, and that lesion at the very top is what a 0.08 millimeter lesion, 80 micron lesion looks like microscopically.
Now, at the time we didn't know this, or we didn't histologically prove it. It has all the other characteristics of the other lesions, I conclude that it is one too, but to prove that we'd of had ... This is about this whole specimen here is less than a centimeter in size. We're sitting right on top of it with a laparoscope, so to cut through that, to verify that, you'd of had to do somewhere between 150, to 900 sections to prove what that was. That is economically not gonna happen, unless you got a research grant to do it. Second, not only is it economically unfeasible, but we can't prove that there is a reason to do it. There is no proof that other than for scientific inquiry that there is a reason to document that lesion, and we'll talk about that more later.
How many of you have seen this slide? This slide has been used for years. How many of you have seen this slide? Okay. For those of you who've seen it, how many dark scarred lesions do you see there? Does anybody see the second one?
It's down below the big one.
Yeah, down ... No, no. That big one is a bowel, but there is a small one down below, dark scarred one down below, on the utero ... So, what's that in the top of? So, to your left is uterer, to right is the ovary, so what's the round structure that it's sitting on top of? That's the uterer. Okay, so we're sitting on top of a uterer, so you got two dark scarred lesions on top of uterer. How about vesicular lesions? How many?
Three, or two.
Two, and then how many areas of abnormal peritoneum? Another 10 that you can count, probably more than that, so if you look at this thing that red one is around the second dark scarred lesion. I looked at that slide for five years before I saw that, and then the two vesicular lesions about the same thing, and then for David's type lesions, when you start talking about abnormal peritoneum, it's all of those, and we let David look at it he'll probably find a few more. I think he's gonna show my dandelion slide just to embarrass me later today, but that's okay. David sees things that most of us will never see. I didn't see it on the dandelions.
Now, let's talk about histology for a second on all of those, because what I said earlier is I don't have data that says we have a need to do documentation at that level. Histology is to evaluate disease. Histology is not to exclude endometriosis. If you see a one-millimeter lesion, your pathology should be able to tell you whether it's cancer, low malignant potential tumor, endometriosis, psammoma bodies, mesothelial proliferation, lymphoid aggregates, and on, and on, and on. They should give you a diagnosis. Do we have a pathologist in here? Yes. You can figure those out, can't you? If I get the tissue to you, you got the answer.
When you get a negative slide from a pathologist, that means that somebody screwed up before it ever got to the pathologist. Either you didn't sample it right, the nurses didn't handle it right getting it off the table, the cutters didn't cut it, or submit it right, but if it gets to the pathologist they can nail this stuff, so if you're getting negative histology there is a problem on the line before it gets to the pathologist. Pathologists don't miss this kind of thing. Negative histology is indeterminate, it tells you nothing. You get negative histology, or somebody who says no evidence of endometriosis, that is no information at all.
If you take the time to do it the only times you're not gonna get the pathologist to tell you what it is, is when you lose the specimen because it's too small. Now, here comes the reward. I have never seen a paper that shows that we get statistically significant differences in outcomes based on histology positive and histology negative tissue. We've had this $100 reward up since 2008 at World Congress on Endometriosis in Melbourne. I want one of you guys to take my $100. Show me that paper. Show me that histology, other than ruling out cancer, and low malignant potential tumor, and evaluating other diseases, show me the histology just to confirm endometriosis is meaningful. It makes me happy, I enjoy the research. It made David happy, he enjoyed the research. A lot of us enjoyed the research, but so far we don't have a paper that tells us what it did, and if anybody gets it approached by clinicaltrials.gov you get $200. Okay?
Most Americans don't quite get clinicaltrials.gov. The only gynecologists I know who have papers approved in that, who aren't PhDs, we'll spot you guys. You guys do this all the time, but all the surgery oriented people are all Europeans. They know about it. We don't know about it. So, now we get back to CO2 laser vaporization. How many of you think that's endometriosis? Raise your hands. How many of you think it's something other than endometriosis? Okay. Now, how many of you think that's something other than endometriosis? That's a carbon briquette on top. How many of you think it's endometriosis now? Come on, David, you get your chance.
It's down there below it.
There you go. Carbon is on the top, so laser vaporization, particularly at this level, if you get down to 50 to 400 watts per square centimeter, you're not using a laser, you're using a blowtorch. It doesn't get the job done, it just carbonizes the tissue on top, hides it at the time of surgery, and then later it's hard to see, so like David says there is our endometriosis on the bottom right-hand corner, so you don't want to use vaporization very often. I wouldn't use it. We quit using it after a while, because it had this kind of effect too much. We went back to excision.
Excision has the advantage of being able to see what's going on, so in this picture we've got the rectum on the bottom left, uterosacral is up above us, we have a little black lesion that everybody can see, and the opening to a pocket. So, we first open up the pocket, and you get to see the pocket back behind there with some old hemosiderin, and debris in there with the endometriosis. Then we open up the second one, so we take that black lesion off. We even find an unexpected pocket back behind that, and then we resect both of them, and that's what a high-powered NC laser at about 5,000 to 10,000 watts per square centimeter is capable of doing. You can get clean excisions. You can take things off. You can save the blood vessels. David does the same thing with monopolar electrosurgery, and in this day and time I would not go back to a CO2 laser, because it's too hard to train somebody to do that.
The equipment is relatively unavailable, and the equipment David uses is available in the entire everywhere, so David does this with monopolar electrosurgery. It gets the same job done. It's a lot less expensive. I'd stick with it. Just a few little things to go along with this. Remember if you look at these dark lesions that the pathologists can't prove, you tell them the wrong thing. Those vesicles are the endometriosis. The brown is hemosiderin. It's peritoneal hemosiderin, and if you look at those the vesicles are glands with a little bit of stroma. If you look at the brown, if you look in that middle picture, if you look hard enough you can see the hemosiderin on an H&E stain, but you need iron stains, so just tell your pathologist that it's got brown peritoneum, that it's full of iron, we need iron stains. They'll do Mallory, or something else, and then instead of a little bit of hemosiderin the whole area lights up with iron.
Last series of things to talk about, look-a-like lesions. This patient had already been on danazol for her endometriosis. She was sent to me. She's got hemangiomas. For all practical purposes, looks like endometriosis. This one had been on danazol for endometriosis ... These were all 1980s, danazol was a big deal then. This one's been on danazol for her endometriosis, that's psammoma bodies. Those kind of lesions also look exactly like low malignant potential tumor, so if you see clusters of vesicles, you see fleshy looking appearances, you see solid white nodules, make sure you get histology on those. Those are the ones we worry about, particularly like that. That's metastatic breast cancer, so we really don't like white nodules. Thank you, and we'll go to questions.
What type of [inaudible 00:25:33]-
No, you don't get to comment until later today. We're gonna ban you.
We learn in Googling endometriosis that Robert Barnes described exam during menstruation in 1873.
And the single digit exam that you're talking about is what was called vaginal touch by the French, in the mid-1800s, so those things have been around for quite a while.
Long time, but you speak French, I don't.
[foreign language 00:26:01]
[foreign language 00:26:06]
I'd just like to say that the most forgotten entity in diagnosing endometriosis is rectovaginal exam. Every patient with pain should have a rectovaginal exam, so you know what you're getting into when you do surgery. Where the patient hurts, that's the area in most cases that you want to excise.
So, Harry and I have disagreed on this for a while. If on vaginal exam with one finger, if you haven't already found everything you're gonna find on rectovaginal exam, you need to improve your vaginal exam skills, because you're closer to the lesion vaginally than you are rectally.
Dan, I've never ordered MRIs or CT scans.
I didn't either, but we didn't have one. [crosstalk 00:26:55]
Just that one finger exam will tell you the tale.
Back in the ways of the dinosaurs, where we didn't have MRIs. Yep. Whether we needed them or not is a different question. I've watched what these people are doing with them now, and they know a whole lot more than you and I ever knew.
I think we have time for one more question.
I said that it's sometimes good to agree to disagree, but we do a lot of sonograms, perioperative sonograms with bowel preparation, and we can identify those lesions completely, and sometimes I'm doing the surgery I cannot find the lesion, I call my sonographist, she go to the OR, do the sonogram, she found the lesion, and I go for it, and we take the lesion out.
So, and these days we have the sonogram, and it has been very good benefit for our patients.
Just a point of interest, what's the smallest lesion that you've seen on the sonogram now?
We could see lesions three to four millimeters in the vaginal [crosstalk 00:28:08].
There is literature on that, I'm just wondering how much ... We're waiting to see if you guys can start doing microscopic lesions with the sonogram.
I don't think so, but we can see that if some retraction.
Yeah. Three, three. Yeah. Three.
We can predict the complexity of the surgery, so we know. I call the gynecologist and said to him, "It's gonna be a difficult one. If you're gonna enter into [inaudible 00:28:31], or genome code surgeon."
There was a recent paper about thickening, and swelling in that area, do you use that sign also?
Of the uterosacral ligaments?
Ah, yeah. Thank you.
Dan, you said you're not gonna excise those lesions anyway, so why do it?
I didn't say I was ... No, no, no. No, no, no. Once I'm in surgery, and I see something, it's gone. That's gonna go, 'cause I'm not gonna wait on histology. That's a different ... That's a prospective question, I'm talking about retrospectively.
So, those tiny little things we used to call [inaudible 00:29:08] endometriosis.
We're still not sure what they mean, right? But we've got data that shows that the volume, and depth of endometriosis is related to the number of patients who have tender nodules, really small lesions are less likely to be tender than large lesions. We have other long term clinical observations that say we can't look at it. It's a pimple thing. You can't look at endometriosis, and say how bad it is. It's just like looking at pimples. You can see which pimple is ugly, you can't tell which pimple hurts. Same model, so when you're looking at it you don't know what it is, so if I'm in surgery, and I see it, it's gonna go. That's a different question.
But just one more comment, before ... I'm sorry. I just would have to add, all poking around, joking around, apart from that, we have to have realistic expectation with what we can find by pelvic exam, and sonograms, and everything.
It doesn't show everything. There is always high lesion on the sigmoid, iliosacral appendix will never show unless you see it, and you should be prepared to do everything in that session. You should have a team approach to the surgery. It's not like 20 years, 30 years right now. Patients do not need multiple surgeries. The team has to be able to handle everything. In our repeat surgery we see quite a bit missed high lesions, and sigmoid, and iliosacral areas, and pelvic sidewalls.
That's gonna be-
And it doesn't show up in pelvic exam, cervix is not that tender, rectovaginal exam is negative.
Okay, so let's talk about that side of New York. New York City, in specific. Let's go out to rural New York. Let's go into Northern rural Mississippi. If you can get in rural Northern Mississippi patients, who have Medicare, Medicaid if they're lucky, and got nothing else, and you can send them to you in New York, and you're gonna accept Tennessee Medicaid. Okay? Then I'm all for you. And the Tennessee Medicare, Medicaid, Medicare. Which one am I on? The one I'm not on.
Okay, so if you accept the other one, then what you say is true, but if the rural Mississippi patients are gonna have to be taken in by rural Mississippi doctors, there is no way in the world that they can set their ORs up the way you set up, so you're talking about local ... I mean, we were talking about the Beamer dealerships, so nationally you need the Beamer index to decide how many IVF units you can have. Okay? You can't have more IVF dealerships than you have Beamer dealerships, but in New York it's not the Beamer thing, it's the Ferrari index.
Let's continue the conversation offline.