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March 8: Q&A with Panel

March 8: Q&A with Panel

March 8: Q&A with Panel

Endometriosis Foundation of America
Medical Conference 2019
Targeting Inflammation:
From Biomarkers to Precision Surgery
March 8-9, 2019 - Lenox Hill Hospital, NYC
https://www.endofound.org/medicalconference/2019

I also had a question for Dr. Lessey about the Bcl-6. I had kind of question you a little bit during the talk. If it's so highly sensitive and specific for endometriosis and if essentially all women with endometriosis will have this finding, is this Bcl-6 endometrial biopsy assay kind of a-

Stand-alone.

What?

Stand alone?

Well, is it the biomarker that we have been looking for to diagnose endometriosis without surgery if it takes a simple pipeline ... office.

I was at a meeting on biomarkers and somebody asked, "Who believes ...", I think it was Christian Becker, "Who believes there's one marker for endometriosis?" And I was the only one that raised my hand. But I think SIRT1 is gonna be a better biomarker because it's there when endometriosis is present, and it's not there when it's not. Bcl-6 is a low-level expression and confuses the story. So, I think with time we're going to transition to that. Plus, as you saw SIRT1 can be measured in the proliferative phase negating the need to do timed endometrial biopsies and perhaps interfere with pregnancy.

Do you ever foresee the Bcl-6 biopsy being a kind of a standard part of the normal pelvic exam or at least in symptomatic people?

I sure hope so.

Yeah, I imagine you would.

So I believe that Bcl-2 is B cell 6 marker which is commonly used in pathology among us for-

Lymphoma.

... a kind of lymphoma.

Right.

A subgroup of lymphomas. And it's just a type of inflammatory marker for us.

Right.

Lymphoid cell marker, a subgroup of a lymphoid cell. So have you ever examined Bcl-6 in the serum for other diseases, other inflammatory diseases or other malignant diseases?

Great question. Yes, it's positive in patients with hydrosalpinges. It's positive in adenomyosis and it's positive in endometritis.

Dr. has a question.

Well, it's exciting to hear two infertilities have such a diverse opinion on endometriomas. I'm curious ... I am observing the same difference of attitudes of infertilities to endometriomas. Forget peritoneal endometriosis doesn't exist. I wonder why? Why can't those questions are never validated with patients and infertility patients when they are symptomatic ever? And how come there is such a diverse opinion about endometriomas? For me, endometriomas are alway ... I have rarely seen endometriomas that haven't leaked, basically. They are all leaking around. And it's all over. It's like hand grenades blasted inside from everywhere, implants or everywhere.

I'm sure you see a lot of endometriomas and probably you get a referral of big ones. We see a lot of suspected endometriomas because obviously it's not proven if you don't have surgery, that is not as large. And we have a lot of patients who don't want to wait and don't to be operated on. So sometimes the decision is the patients. And I think one thing that's really important for us to, everybody around this table is involved in patient care, is not to take away the decision from the patient.

We have seen ... One of the problems I have with some of the studies that Dr. Lessey presented ... He may not want to sit next to me ... Is the fact that when you look at the study that does surgery and has pregnancies afterward with no control group, the study from Stanford, I think, being one of them. And even the study I presented from Israel is another one. It's very hard to say ... Because, you know, pregnancy is very common. It's actually more common than endometriosis. So patients get pregnant. Patients get pregnant. They get pregnant on their own. They get pregnant with this kind of treatment or another type of treatment. And to relate surgery and to say, oh, you know, you have to take people and kind of bring us back to before the journey editorial to diagnostic laparoscopy the way we did it when we were fellows and basically scope everyone that's walking around with unexplained infertility because Dr. Lessey thinks that most of them have endometriosis but doesn't have any proof is a question.

We do have proof. We did the study, and we have a study in human reproduction where we laparoscopic patients with unexplained infertility and unexplained loss who were positive. But, I think, getting back to the endometrioma question, even these small endometriomas can cause IVF failure and yet it's outside the scope of what guidelines recommends. We shouldn't operate on them if they're not above 4 cm or if the patients are asymptomatic. And this woman, Beth, from Bethesda, who came down to see and had spent $120,000 doing multiple IVFs and three donor egg retrieval cycles, she conceived her endometriosis was removed with her next transfer. Anecdotal of course, but with this test that we're doing now, we're getting reports from all these centers that they're seeing dramatic improvements in their implantation rates with just two months of Lupron. So I think that's why we got the SBIR. That's why we're gonna do the randomized control trials and we're gonna have the proper controls in the next two years to validate this test.

So, I'm going to ask you a question. Your story today was incredibly inspiring and provocative. And that you can find these cells throughout tissues in the whole body and maybe in the brain, etc, and obviously that men can get endometriosis. What is so special about the endometrium, do you think? Because there are other chronic inflammatory diseases like IBD and so on where you have this constant wound healing, probably some of the same processes. Do you expect that you might find cells, intestinal cells in other places in the body?

You know we've never looked and I don't know that anybody's ever looked. I would love to have the answer to that question.

Yeah, so I think we should get some people to do that.

Yeah.

Because is it a common thing that you've discovered or is the endometrium so special.

I think there's a lot more cell trafficking going on in all sorts of organ systems than we ever imagined. That would be my suspicion.

Let's find somebody to do those studies.

But no other organ is bleeding every month.

No, that's the question. 

That's the process. There's a furnace every month. There's a furnace there.

That's the question, but if they're coming from the bone marrow, there's a very interesting

Intestine's not going through that state. There's always monthly injury there and constant repair.

Yeah.

It's a wound that heals there.

Yeah, we don't know what.

The endometrium is a wound that never heals.

We don't know cycles in the female.

Can I also add the endometrium and the kidney are the two tissues that populate epithelial cells not from existing epithelium but from mesenkine bone marrow derivatives. So the bone marrow link is real and probably embryologically driven.

And we've seen some big changes in endometrial stem cell recruitment pregnancy. It may be a special adaptation to the changes, the physiologic changes, that are required for pregnancy that's a huge remodeling of the uterus that's really unique. I don't know if we'll see it in every organ system with every cell type we look at. But I still think there is a lot more cell trafficking going on than we suspect.

First of all, thank you to everybody. I thought the talks were excellent. Oh, sorry, my name's Melanie [Marin 00:09:03]. I'm a gynecologic surgeon at Mt. Sinai and I do mostly endometriosis. I was trained by Harry so I have my biases there also. So, thank you all. And I wanted to just sort of comment/question to Dr. Lessey. I think what you brought up is so important. And I think the one thing that we miss all the time when we're talking to our patients but should you have surgery first or go for IVF first is the cost. Because some of these patients are spending hundreds of thousands of dollars. And if you only have x number of eggs, or if you're 39 1/2 and you're on your way down for your infertility, I think having surgery first to maximize your chances makes a lot of sense. And it's nice to have some data to sort of help with that. My talks with my patients have been mostly like, how many thousands of dollars do you have to spend before you do surgery, or eggs do you have left before you do surgery.

Yeah, I think that surgery is a good opportunity to help patients get pregnant without IVF. And for those who can't afford it, that would be a good option.

Or self-pay IVF.

Hi, Dr. Lessey. Thank you guys for all coming. I have a second mic, sorry. gave it to me. Dr. Lessey, just a simple question. The biopsies that you did with Bcl-6 and then success afterward, was that after laparoscopy and after Lupron, was that in the same group study? Or was that independent? Maybe I missed it.

It was not a good study design. It was non-randomized, at the choice of the physician and the patient. But we found, what was it, ten Lupron patients and 21 surgery patients and compared them to 54 women who had not been treated. All of the women were Bcl-6 positive.

Hi. Amy Jane. I've come from France. I guess you'd call me an expert patient in that I'm 40. It started when I was 14 so that gives me 26 years of experience. And just one comment on the depression side of things. I'm just wondering how many life factors can be taken into an account for a mouse when it comes to depression. Because, obviously, from a patient advocate point of view, there's quite a lot of involvement with changes in lifestyle, changes in life possibilities, changes in life path, changes in what we thought we were going to be living and we find ourselves. Particularly at different stages in life because no one tells us at each stage because we don't know. Another point is if you need a specimen, I will be your specimen with regards to intestinal sample because I just said to my gastro, my Calprotectin is over 500. It should be 50. Surely that's interlinked with everything else as well. So I've got ... Probably to talk another time, but I've got quite a long case history that may be of interest to you also. I will be your real life mouse.

That's a good point. Mice aren't humans. That's obvious. And I think ... But the fact that we prove that the endometriosis actually causes changes in the brain that lead to depression, anxiety, pain sensitization, shows that there really is ... It is a biological effect, the disease. It is not just a social situation. That, I'm sure, compounds it and makes it a lot worse in humans than in mice. But it has an underlying biologic basis.

First of all, my compliments. The level of brilliance of the panel and the exciting work you're doing is truly remarkable. One comment is my guess is the endometrium as it relates to estrogen is a different environment. Estrogen in the whole body tends to be more anti-inflammatory in cardiovascular, in the entima of the epithelium, in the pre-Alzheimer's biology and cutting down glial cell inflammation. So probably it has to do with the particular relationship of, as you've brilliantly pointed out, the estrogen receptors down, regulating the estrogen receptors cuts down the inflammatory marker in the endometrium. And I must say, perhaps Lupron and the antigonadotropins are going to make a comeback because of the relationship that you've all brilliantly shown between downregulating estrogen and lowering the inflammatory markers, so my compliments.

You know, the best treatment for endometriosis would be a good anti-estrogen. But they really haven't formulated the breast cancer drug for daily use. It's a Depo shot and I think if some pharmaceutical rep out there could help develop a daily anti-estrogen that would be a miracle drug.

Can we publish a paper on that?

Just a comment about, I had a lecture about the nerves this morning, you'll remember. I have some difficulty to accept and to connect endometriosis with depression. Because my patient with cancer have also depression. All patient affected by the disease has depression. So depression is not connected to endometriosis. Depression is connected with the overactivity of the sympathetic nerve system. In all men in this room, if I put an electrode on the system, sympathetic system and I increased the activity of the sympathetic system, we will all become depressive. I'm dealing with a paraplegic. I'm putting an electrode on different nerve paraplegic. We change the mode of the paraplegic if I'm putting [inaudible 00:14:39] depending on the frequency. But from a depressive paraplegic, I can make a nondepressive paraplegic. So it's not connected to the endometriosis or endometrial cells in the brain. It's not a pathology. It's a normal way of seeing when you have overactivity of the sympathetic nerve system you will become depressive.

Thank you immensely for those comments. That was really important to say. Alright. We should wrap up this discussion. Thanks for all the great questions and discussion. We'll have a coffee break now.