Virtual Medical Conference 2020:
REOPERATIVE ENDOMETRIOSIS
Dr. Tamer Seckin:
I'm Dr. Tamer Seckin from New York City. Ladies and gentlemen, welcome. A warm welcome to you all. I recognize you all. Our virtual conference with tremendous excitement, since we went through a unbelievable year with COVID. We named this conference as, "The Truth is on the March, and Nothing Will Stop It." In fact, something stopped it and that was unfortunately COVID. We never had anything like this. Unfortunately, COVID bring us the COVID mortis. While we were searching for endometriosis, we met COVID mortis. Actually, Corona mortis is something that is medicine where epigastric arteries connect to the obturator vein. There is an anatomical position there. I wanted to mention that since this is about Corona. It was an interesting meet there for me.
Something happened, and science was the winner. Science preceded the politics. So I like to tell you just a little bit. This is our 11th meeting, and I like to acknowledge my co-founder Ms. Padma Lakshmi. This is a picture from our first ball, when we had in 2009. Padma has a lot to do with our foundation's initiation. She basically brought it to the visualization throughout the world. Through her courageous discussions about her own disease, which is a public, where I had been part of her surgeries and her story.
She was the first one who really started talking about her internals, with courage, like Betty Ford did about her breast cancer 30 years ago from that. So endometriosis found significant recognition. And I must say that since we started the movement with the foundation, there has been multiple cert endometriosis centers opened up, research increased, and I must say many physicians have more courage to go after endometriosis like they never did before.
Right now, the foundation has done significant progress. One of the key progress has been, we have donated $1 million for research. Couple of our research awardees was qualified for more millions of dollars of NIH, NIH. And on top of it, one of the key achievement I must say, our high school program got recognition in Albany, and there is a Bill New York State passed as recognition of endometriosis as a disease associated with menstruation. And high school kids will learn it. We aim to spread this throughout the nation.
Well, this is a picture from our first ball we had and Harry was recognized. He didn't know that was a surprise for him. Today, he will be part of our presentation team. I am joined by esteemed faculty and speakers. This is a two-day conference and the first day we're going to cover uterus, extra pelvic and cancer and neuropathy. And our keynote speaker and the recipient of Harry Reich award this year, Dr. Arnaud Wattiez will be joining.
But before that I introduced my moderators doctor, Dr. Dan Martin, Dr. Reich. And I'm not sure if he is here, but Victor Gomel. Harry is in Florida. Dan Martin is in Washington and Victor Gomel is in Vancouver. I like to have, more importantly, before we continue my Department Chief Dr. Frank Chervenak, the world-renowned ethicists, the man of moral and good-hearted person has extended his help and assistance throughout his life to everyone. I want him to say a word, because if it wasn't his support, maybe we couldn't ... I couldn't be doing much of my practice at Lenox Hill Hospital.
Dr. Frank Chervenak:
Morning. Good morning to everyone! Tamer, good morning! It's a pleasure and privilege to welcome everyone this morning to this moment of beauty in this troubled time. All of us, I know Tamer, myself, everyone on this webinar would rather be meeting in person, so we could share the wonders as we did in past years. And Tamer hopefully next year, we'll meet in person to celebrate. But I think it's wonderful that we're doing it this way in these challenging times.
A special word about Tamer Seckin. I am the Chair here at Lenox Hill and I'm very proud of this department. And I'm especially proud of Thomas Seckin. He is the classic triple threat. He's a brilliant clinician, he's a brilliant researcher and a brilliant educator. I could go on and on of what he contributes, just not to the patients. He helps people from throughout the world. He trains our young doctors and he's putting new knowledge forward. Please, I wish every doctor in the department could be like Tamer Seckin. He's a role model for everyone, for all of us. And Tamer or I'm so grateful to you for what you've done in this challenging time. You've brought together the best people in the world. Some of them have pioneered endometriosis surgery from the beginning. Some are newcomers. But you brought together the best, to assure that anyone who is calling into this will be enriched and will be better able to care for their patients. So without further ado, I welcome you all. I congratulate you for being part of this. Tamer go forward. Congratulations to all of you!
Dr. Tamer Seckin:
Thank you Dr. Chervenak. So we are officially starting our conference. As you know, the first day is divided into ... It's a two-hour session. And the first are, there will be Dr. Philippe Koninckx from Belgium will be starting with pathophysiology of endometriosis. And Errico Zupi, we're going to cover his talk with questions asked. And then there will be again, Dr. Tulandi and Nezhat's. And we have recorded the presentation of Dr. Wattiez and his award ceremony. And then we're going to go for .... We're going to do all these things, believe it or not, in the next two hours.
So I like to introduce Dr. Harry Reich for his contribution to endometriosis. I don't think anyone who does laparoscopic surgery in the world is not familiar with Dr. Reich. It is his first hysterectomy in 1988 or '89. I met him later, a couple years, maybe five years later in Hawaii. Then we became friends. But throughout that, I can tell you, Harry Reich has been the power of spreading the word endometriosis and laparoscopic surgery, especially in the world. And many young doctors, including myself, have met these giants, Dr. Ray-Gary, and Frank years ago. And here we are in Belgium. This is 25 years ago. Arnaud Wattiez is sitting right across me. That's the first time I met him. He was Brouha's student. Everybody respected Brouha with ..., I am hearing more and more from Dan Martin. But Harry was this incredible man that really traveled around the world. I learned stitching from him that nobody else ever did like that. Nobody put that curved needle inside. And he was incredibly meticulous with hemostasis.
And these are still the most important aspect of laparoscopic surgery. I also would like to recognize if he's not joining us right now, Dr. Victor Gomel. He is also one of the giants. He'll be one of the panelists later. Microsurgical techniques that he introduced in concept and practice has been the key of laparoscopic surgery that really prevents adhesions and directs precision in the best way we remove these disease.
So without further introduction, I like Harry, start talking about his piece which was, "In my life I saw it all." I reviewed the video. Fantastic! Unfortunately, due to time constraints, we cannot present, but I want him to talk about why he presented the pieces. He has shown his abscess case and very difficult bowel case that he started. Actually, Harry is the first one that I know that use the stapler in bowel late 1995. Harry, please join us right now. Thank you.
Dr. Harry Reich:
Thank you! Anyway, I want to thank you. It's unbelievable that we've gone two years without seeing many of you, because of this pandemic, which is terrible and continues terrible. I haven't gotten a vaccination yet, but I hope many of you have started on the vaccination for this condition. But anyway, the title of this whole day is about reoperative endometriosis. So in the videos that I presented the first one was what happens if you do have a late complication? Namely perforation of the rectum, which happened in this case ... I think it was day eight after surgery. After what I call "skinning of the ball".
First of all, let me say that, from the early days I was excising endometriosis, and especially endometriosis, thinking that was the key. And later on, I discovered that wasn't the right solution. The cul-de-sac was more like it. And just separating the rectum from the vagina helped in many of these cases. But some of these cases recurred, and we went back in these cases and excised the nodule, usually on the back of the cervix or the back of the vagina. And it wasn't until around '88 or '89 that we started being aggressive toward the rectum.
But really, endometriosis to me is a recto-vaginal disease. That's where it lies. So, between the uterosacral ligaments ... First, you start with a uterosacral ligaments, and then what's between. So, that's where the disease lies and the rectum is there, believe it or not! We're gynecologists. We're taught not to go near the rectum, but I think the time is present where we have to be better trained. And as Arnaud will emphasize, we have to become pelvic surgeons. That means excising the rectum if it's involved with the disease. And in my second case, I show a case where not only was the rectum involved, but also the sigmoid. So we did a sigmoid resection through the rectum, for the first time. I think the only time. I haven't heard of that technique since. But anyway, that's why I don't present these things at meetings or journals. But you'll see the video and that should give you an idea of what we did.
Tamer, I'd like to say, it's great for me to see Victor Gomel here and Philippe Koninckx, and I'm really looking forward to Arnaud. I think you will see Arnaud's whole tape of his case, which ... Not only his case, but his philosophy, which is similar to mine. I think unlike Dan Martin, who we're very privileged to have as the Medical Director now of the Endometriosis Foundation of America.
So really we have, besides this great organization that Tamer started ...Now we have a medical director who's respected worldwide. So we'll talk about this stuff. But for me, I'm more like Arnaud when he talks about "Find the disease, see the disease, excise of disease." As far as the microscopic portion, I'll let Dan talk about that in more detail. But I think endometriosis is a lesion that causes the pain. It's a lesion that's surrounded by fibromuscular tissue, and the key to it all is the fibromuscular tissue, which is easy to see and easy to grasp and easy to excise. Well, not easy. It can be quite difficult going way deep into the pelvis. So ...
Dr. Tamer Seckin:
Thank you, Harry. Dr. Martin, you may have some questions. We have to engage some of the questions that may be directed to Harry since he has a different and solidified vision of certain things. Do you have any questions that coming from the audience?
Dr. Dan Martin:
So we're watching the questions right now. None have been directed to Harry at present.
Dr. Harry Reich:
Thanks!
Dr. Dan Martin:
We do have one. Let's see. I'm getting an echo. Where's my echo coming from? I can't figure out where the echo is coming from. Anyway, we do have one regarding the $26 million ... The question was about 63 million. I wish that were true, but it's about the $26 million grant-
Dr. Tamer Seckin:
I will answer that if you don't mind.
Dr. Dan Martin:
Okay. Yes.
Dr. Tamer Seckin:
I think the amount is totally incorrect. Foundation never gets money from the government. Foundation do not get any money other than small amounts in the past, from any insurance company or any other pharmaceutical. So the amount of money that's been authorized this year, through our also effort, among others, is 26 million. And that money is going to NIH-directed researchers. So let's clarify that. So foundation's economical income and every paper that's related to it's finances can be found. It's very transparent. It's in the website until 2019, included. You can go and check it there. Anyone interested. Thank you.
Dr. Dan Martin:
Thank you, Tamer. Harry, here is a question that you can answer. Some women after endometriosis surgery, even after resection of everything that is seen, still have pain. What can they do about pain after they've had surgery?
Dr. Harry Reich:
I have very little experience in that situation. Most of the time, if I could find it, the endometriosis, with an exam ... And I emphasize a good recto-vaginal exam. You could usually find where the patient hurts. And that's the area that you concentrate on during your surgery. And if that area's excised, in most cases, the pain will be relieved. If it isn't. Again, I'd send her to a pain specialist, I guess. But I was an endometriosis excision specialist, not a pain specialist.
Dr. Tamer Seckin:
Thank you Harry. I think for time-related issues, we need to move on. And I'm going to move on to Dr. Philippe Koninckx, who has a beautiful video in our website and in our server. It's about the pathophysiology of endometriosis and adenomyosis for clinician. Dr. Koninckx says, "There is a need for a valid contemporary understanding of endometriosis, since the standard definition as endometrium-like glands and stroma outside the uterus, is old. About 100 years old. A century." So he thinks it's very outdated and it does not validate all the clinical presentation. Dr. Koninckx, you have the floor.
Dr. Philippe Koninckx:
Thank you, Tamer. Thank you for the invitation. Thank you my friends all there. I'm not going to list you one by one. Do I give a talk of three minutes or can I show a video?
Dr. Tamer Seckin:
Thank you. We're going. And then there'll be questions.
Dr. Philippe Koninckx:
Yeah, just just five slides. If I share screen. That's it. Share. You're going to see many of these things I have been been discussing for years and with Dan Martin and with Victor and with ... Okay, all the quarters. But what for the audience, I would like to specify facts and hypothesis. An observation that an apple falls down and never falls in the other direction, you make a hypothesis. Every time you refine. You find other observations. It remains valid until one observation does not fit. And if you need more than one hypothesis, probably it's not correct. I have a problem with macroscopy and microscopy. Everything it does is ... Only thing you can say, "It looks like ... ". And there you go from the body to the organs, to the tissue, to the cell or a cell machinery, epigenetics. And then you have more like a biology, DNA, epigenetic cell machinery.
Dr. Philippe Koninckx:
And this is an impression, and this we still don't know about endometriosis. That's where things are coming together. The definition of as you said Tamer, it's 100 years old and it's not really valid. It's not always pathology. The Sampson's implantation theory is that the second thing. Today, it's history. I think we can forget this, because it does not explain that metaplasia. It's incompatible with clonality and it cannot explain a lot of things. All what is association. Association can be ... Endometriosis can cause changes in peritoneal fluid and all these changes can cause Endometriosis. Or you can have a common cause. This is the reason why together with the quarters we published, genetic means it remains endometrium until something change. And at that moment you could call it and the endometriolic disease.
Dr. Philippe Koninckx:
What is driving this is oxidative stress. I'm not going to dwell on this, but probably infection. And you have to remember, that the inside of the peritoneum is outside the body. It's like the inside of your mouth. It's outside the body. There's no vascularization inside there. It's outside. So this is the whole study of the microbiome, which means that it comes to ... This as a story inherited defects. This is including and endometrium infertility pregnancy problems. These are the cause, what causes during life. More mistakes. And then you have a lesion and each lesion is different. If you have 10 lesions, you have 10 different clones. And each lesion is different and some have progesterone resistance. Other estrogen production.
Dr. Philippe Koninckx:
The nice thing for the clinician. And that's two last slide. I want to show. If we could go to prevention, less pollution, less oxidative stress, less blood in the peritoneal cavity, maybe antioxidants may be manipulating the peritoneal microbiome. And you see already there, you have the story of food intake and exercise [inaudible 00:23:37] manipulates the microbiome. And it's the first time I begin to understand that this could help with endometriosis.
Dr. Philippe Koninckx:
So these are the hypothesis. Oral contraception helps on all the levels, antioxidants, food intake, and exercise. But if it's benign tumor, you have to do surgery. A very challenging, since if you get half a meter of bowel or just excise nodule, recurrence rate is the same. I only can explain this, is a periphery of the endometriosis is some kind of fibrosis of metaplasia. Maybe it looks [inaudible 00:24:18] metaplasia and it's also the same thing with, for oncology. But this means that ... Or surgery in the future should be much less aggressive than we are used to do. That's it. That's the message.
Dr. Tamer Seckin:
Thank you Dr. Koninckx. Dr. Martin, is there any questions pending or in your file for Dr. Koninckx, or related to this talk? I must remind all our viewers that we do not have to cover all the questions. We have in our roster, 150 questions. It's even hard to categorize them. But we're trying our best, but trust me, we will try to answer those questions after the meeting separately, by our special efforts. Dan?
Dr. Dan Martin:
Yes. I'm reading the questions right now to see if someone has sent one to Harry, I mean to Philippe. Okay, Philippe. I don't find one specific for you, but here's one that crosses over into both endometriosis and adenomyosis that may be a reasonable question. Someone's been diagnosed with adenomyosis and wants to know what that means? And could you answer that with respect to, how are adenomyosis and endometriosis associated with respect to the theories you just discussed?
Dr. Philippe Koninckx:
Women are born with some kind of genetic, epigenetic defects which means that if you already have some predisposition and you have more likely to have additional risk of both adenomyosis and endometriosis, which to a large extent are very similar conditions. [inaudible 00:26:23] They are only different by location. But the condition itself, I think it's the same thing.
Dr. Dan Martin:
Okay, Philippe, here's a specific question from our champion Togas Tulandi. He wants to know what type of food do you mean that women should or should not take?
Dr. Philippe Koninckx:
I didn't hear the question. I didn't understand.
Dr. Dan Martin:
You mentioned food and your presentation.
Dr. Philippe Koninckx:
Okay. Food. I know it's very provocative when I say this. It seems logic that the oxidant should be helpful for endometriosis. It's logic. If I look at the many papers which are being published about food and endometriosis, it's more than to say this myth, it's not true. They come from India. They come from China. There are a lot with [inaudible 00:27:24] there are a lot of data that food is doing anything. I always have been thinking, how good could food do anything for endometriosis? But I was surprised during the literature on the microbiota in the peritoneal cavity, that food intake is going to change the microbiote in the peritoneal cavity. As does exercise, because it manipulates the microbiota in the bowel. And there's some kind of transmural progression of ... The bacteria in the microbiota is going to go transmural and affect the peritoneal cavity.
Dr. Philippe Koninckx:
So the nice thing about this is that the day we understand, it comes together. and I think it becomes logic to look closely at food, and to do nice randomized trials for this in order to know what helps or does not help. I must say I am starting to be interested in the Indian, Chinese literature. Exactly for this.
Dr. Tamer Seckin:
Thank you. It's time maybe. Okay. There is a question. I think I'm going to direct this question, Dr. Gomel. Someone [inaudible 00:28:44] is asking you, what are the ways of minimizing adhesions and scar tissue following a second surgery? She's not mentioning about the first surgery. Apparently, she is going maybe for a second. She's afraid it may come back again. Dr. Gomel, this is your field.
Dr. Victor Gomel:
First of all, I would like to say a few things about you. You are a phenomenal and I have always said that. The way you have taken, first of all, endometriosis as a sole specialty, the way you have created a foundation and you're talking in millions of dollars. This is fabulous achievement! I thank you! I congratulate you! And I'm very proud that you invite me here, I am honored!
Dr. Victor Gomel:
So coming to the [inaudible 00:29:58], what you have to do in the first surgery ... It's exactly the same as the second surgery. You have to use exactly the same principles. And for me to tell you all the principles will take a lecture. But I can give you, if you want, places to look at. Fertility, sterility. From laparoscopy laparotomy to IVF. There you see all the principles that we worked on to diminish adhesions. And the first thing are the very gentle surgery.
Dr. Tamer Seckin:
Thank-
Dr. Tamer Seckin:
Thank you, Victor. Thank you very much.
Dr. Victor Gomel:
[crosstalk 00:31:06] to take the time, but these are principles and there are many of them.
Dr. Tamer Seckin:
Dr. Reich, do you have anything to add or say about the adhesions after surgery?
Dr. Harry Reich:
Well, there're all kinds of things that people discuss about adhesions, and my thing was always to use Ringer's lactate. My solution to pollution was solution, so I would leave a 2000 cc's Ringer's lactate in [inaudible 00:31:41] cavity at the end of every case. I believe that has a hydroflotation effect and that it markedly reduces the amount of adhesions that one will get after surgery.
Dr. Tamer Seckin:
Harry, there is one question popping up. You can talk about it for hours on this, but this is a good one and well-positioned by Amy Jane [Melhuish 00:32:08]. I do not know where she's from.
Dr. Tamer Seckin:
Interesting presentation, Dr. Reich. I watched it. Would love to hear yours and the panel's views on pros and cons of robotic or not surgery when considering you're feeling the disease, another haptic feedback, versus being able to visualize microscopic disease with robots. Also, she continues. There is another question following this. What do you think about excision versus ablation? We know the answer, but you can say it. Go ahead.
Dr. Harry Reich:
Well, I don't know that much about ablation other than every now and again, besides the major lesions, and there're still a few areas of endometriosis that will ablate, especially when I was using the carbon dioxide laser. As far as the first question, what was that again, Tamer?
Dr. Tamer Seckin:
The first question was about robots, the role of robots. What do you think about robotic surgery's place in endometriosis, particularly because it's a haptic feedback that really we rely on in endosurgery?
Dr. Harry Reich:
Well, I found that feel was always very important for me. I could feel normal peritoneum and I could feel deep fibrotic endometriosis inside the peritoneum or on the peritoneum. I could grasp that and excise it, and with a robot, I can't do that. As far as whether I could see more endometriosis with a robot, I'm not sure about that. Remember, I started without video cameras. I used my eye.
Dr. Victor Gomel:
We all started that way.
Dr. Harry Reich:
Pardon?
Dr. Victor Gomel:
We all started that way.
Dr. Harry Reich:
Not today, but we did. Most general surgeons who do any of the bariatrics or any of the other things use video right from the start. But for us, Victor, we started with our eye. We had to look with our, eye and then we came upon the beam splitter. I used the beam splitter and I didn't trust the camera, even though everybody else in the OR saw on the screen what was going on. I didn't believe it, so I continued to use the beam splitter. When I did my first hysterectomy, in fact, I was looking through a beam splitter, so I did most of it with my eye.
Dr. Harry Reich:
Some time around the early '90s, I started using video more. But I think the robot, according to the literature, you see even more than you can with looking at the sharpest video. I have questions about that because again, I haven't much experience with the robot, but I see what people are doing with their videos, especially with now that you have 3D video coming upon us. They could see the whole pelvis. They could see the lesions quite nicely. I'm not convinced that the robot really offers anything, and I do like the saying that I've heard from many others, that it seems to be training wheels for the laparoscopic surgeon.
Dr. Tamer Seckin:
Thank you, Harry. Thank you very much. This conversation and discussion about robots, again, can go on and on and on. I also believe there are good robotic surgeons coming up. It really applies very well to direct hysterectomy and myomectomy, and some people are doing good surgery with endometriosis too, but I think it's a matter of who's on the driver's seat and what vehicle they're driving. We have to move on, but there is one question that we will delay over to Errico Zupi. Errico is not feeling well and could not join us today, but it's about adenomyosis and Osada procedure. The person is asking, why don't we do Osada procedure? I will delay this question and answer later, but it's a good question, but we have to move on with the extrapelvic endometriosis panel. We are joined by Dr. Togas Tulandi and our good friend, Dr. Farr Nezhat, from New York City. Togas Tulandi is joining us from McGill University, Montreal, and Farr is probably very close to where I am right now in New York.
Dr. Tamer Seckin:
Hi everyone. Hi Togas. Hi Farr.
Dr. Togas Tulandi:
Hello.
Dr. Tamer Seckin:
Nice to have you today. I think I will start with Togas's presentation. He goes after something we know that ovarian cancers are common, the tubal reverse trafficking the cells, drop to the peritoneal surface. We know that association, we know the rate. What Togas is making interesting point, more the endometriosis association with tubal cancer and other adenomyosis. Togas, you have the floor. Try please to restrict as short as possible because there will be questions popping up and Farr is also going to talk. Thank you.
Dr. Togas Tulandi:
Thank you very much, Tamer. It's great to be here with you guys, although virtually. Of course, I'm happy to see all the friends, Harry, Victor, and Dan. Basically, we did a study and it's a large epidemiological study looking at the association between endometriosis and ovarian, which already described before. Also, we look at tubal cancer. We found that endometriosis is also associated with tubal cancer. We also looked at adenomyosis. Now, Philippe mentioned about adenomyosis, and we found that even adenomyosis, to our surprise, is associated with tubal cancer and ovarian cancer. Now, I don't want to make everybody nervous, but the incidence is low. It's about one in 10,000 women. But in the presence of endometriosis, the incident is higher. But the good thing is if a patient has endometriosis, well, the bad thing is they get cancer earlier, but the prognosis is better. It looks like it's better. I'll stop right there and then I'll answer questions if there is any.
Dr. Tamer Seckin:
There's a specific question that's coming to you, Dr. Tulandi. Do many of your patients first treated for endometriosis return with ovarian or endometrial cancer?
Dr. Togas Tulandi:
The problem is this database is a large database. It's not longitudinal, so it's just a trend. So, it's not Mrs. Smith is being followed for 20 years or so. It's not longitudinal data. It's just a trend. I cannot answer that specifically.
Dr. Dan Martin:
Oh, there's a question about family history of ovarian cancer. What is the increased risk of ovarian cancer in women with endometriosis? Can you do that both in relative and absolute risk?
Dr. Togas Tulandi:
I don't think we have the answer. One thing we know that endometriosis is familial. In Montreal, we looked at it. It's about 8%. In UK, it's about 7, 8% as well. There is a familial tendency of endometriosis, so maybe there's also a familial tendency of endometriosis and ovarian cancer. We don't have the answer.
Dr. Tamer Seckin:
Thank you very much. I'm sure Dr. Nezhat cannot wait to take his turn and address some of these questions also. Farr, I'd like you to summarize your fantastic presentation in a couple of words. As you all know, Dr. Nezhat is one of the few GYN oncologists whose interest and focus is on endometriosis, which we don't really see much. GYN oncologists typically run away from endometriosis. They really don't want to see because for them, it's waste of time and it's difficult. Farr is special in that regard. I think he will address some of the questions. He actually, in his talk, treatment and screening options are available for women with endometriosis. Farr, the floor is yours.
Dr. Farr Nezhat:
Morning. First of all, thank you very much, Tamer, for the kind invitation to be part of this distinguished faculty. There are two issues. One issue is the patient had genetic alteration. You have to identify if it's in your family history or genetic alteration. This is the most important thing to know. For the patient, your background is genetic alteration to cancer or sporadic cancer. Endometriosis, as you all know, is an inflammatory, estrogen-dependent disease, and the baseline of the legal transformation of the cells are two new things, is estrogen, inflammation, and somatic alteration of the endometriosis cells. But it means that endometriosis cells already have some molecular alteration. They are one step closer to become malignant. If you add to it estrogen and also inflammation, which is hardly more common in endometriosis, makes this lesion to have tendency to become malignant.
Dr. Farr Nezhat:
The same way that endometrium has potential to become malignant and have endometriotic adenocarcinoma, they have clear cell carcinoma. We have serous carcinoma. We have stronger adenocarcinoma and [inaudible 00:43:36] or malignant mix with a [inaudible 00:43:38] tumor of endometrium. The same way the endometriosis cells, they're on the ovaries, or on the peritoneum, on the bowel, other areas, could become malignant. That is a simple background. Now, if the patient does not have any germline genetic mutation, it is an instant malignant transformation, as Dr Tulandi mentioned, is low. It is maybe 1 to 2% higher than general population.
Dr. Farr Nezhat:
In the same time, we have to realize that we have a different type of histology, and particularly ovarian cancer. Majority of them are high-grade serous carcinoma, and then the next one is endometriosis, and then next one is clear cell and [inaudible 00:44:43]. High-grade serous carcinoma seems coming from fallopian tubes, from affiliated ends of fallopian tubes. That is one of the biggest discoveries that we have made in recent years, that particularly, high-grade serous carcinoma, the origin majority of them is not ovary. It is fallopian tube. That is the reason that we have not been able to find a good screening test like AutoSound or CA 125 to find this cancer earlier.
Dr. Farr Nezhat:
However, endometrial and clear cell carcinoma are coming from the ovaries, and those backgrounds, it seems most of them are endometriosis. It is really simple. You have endometriosis. That already has the cells, so molecular alteration. They have high level of the estrogen in the ovaries, or even endometrial implant itself has a high degree of [inaudible 00:45:55] activity, produces a lot of estrogen, and of course it has inflammation. These three together make these lesions become malignant.
Dr. Farr Nezhat:
Now, we know that the patient has germline molecular alteration. The most common one is BRCA1. We are seeing two. Other molecular alterations regarding the next group are Leriche syndrome, there are four different protein abnormalities, and somehow they want the rare one. Those who're going to have it have a higher chance of the ovarian cancer, which most of them are high-grade serous carcinoma. For example, the BRCA1, which has the highest number of the potential to develop ovarian cancer, is about 35 to 40% that this patient has potential to develop ovarian cancer. If we are suspicious, that this patient has one or two people in the family having Hawaiian cancer, these days, we are doing germline, blot tests, or saliva, genetic testing. If the patient has this alteration, she has to be consulted by a genetic counselor. We add wise to have well for ectomy. For BRCA 1, we advise them... What age are y'all? 40, BRCA 2, age of 45, to have all four ectomies. Hopefully by that time, they have had their children.
Dr. Tamer Seckin:
Thank you, Dr. Nezhat. Thank you so much. There is one question actually directed to Dr. Ayhan. Dr. Ayhan is in Japan. She is sleeping, most likely. It's three o'clock in where she is. So, that question will come to you guys. Is there anything endometriosis patients need to advocate for in terms of tests and procedures to risk ovarian cancer? Also, I will add my question to you. In your private practice, when patient requests prophylactic oophorectomy with history of ovarian cancer in the family, it is actually justified. It's an elective procedure. Do you do peritonectomy of the anti-ovarian surface? Two questions. Please help me to answer it fast because we have to move on. Thank you.
Dr. Togas Tulandi:
Yeah. I think the implication of our study is we have to increase vigilance in women with a history of endometriosis. If there is something suspicious, I think we have to be more aggressive in these patients because there is slightly a risk of ovarian or tubal cancer. The other question is what, again, Tamer? I'm sorry, I didn't get it.
Dr. Tamer Seckin:
The other question is, in surgical practice, does it make sense when you do prophylactic oophorectomy? We know [inaudible 00:49:29] is prophylactic. When you do prophylactic oophorectomy, do you consider taking anti-ovarian peritoneal sidewall as abnormal you can see visualize? Or you just leave it? I tell you what I do. I remove. But you go ahead.
Dr. Togas Tulandi:
Usually I remove the ovaries, and if there is a lesion on the sidewall, I remove it. If it's normal, I don't do anything, of course. Maybe Farr can elaborate more.
Dr. Tamer Seckin:
Farr.
Dr. Farr Nezhat:
If you do prophylactic oophorectomy for patient, it has genetic alteration. The most important thing is to evaluate the peritoneal cavity to be sure there is no gross abnormality. Any gross abnormality has to be biopsied, and then we do peritoneal washing, and then remove both tubes and the ovaries, and the pathologist has to do cellular section of the entire fallopian tube, and also the entire ovary because the patients that seem to be have normal tubes on the ovary, histologically, they could have up to 2 or 3% of macroscopical cancer. For the peritoneum, if it is abnormal, yes. Any abnormality of the peritoneum has to be biopsied in a second, but not normal peritoneum.
Dr. Tamer Seckin:
Thanks you. Dr. Martin, do you have any questions on Slack? Online live question coming.
Dr. Dan Martin:
How do you approach surgery in this day and time of COVID-16? What do you do to protect them? Do you think they should all have vaccinations? What other concerns do you have?
Dr. Togas Tulandi:
Good question [inaudible 00:51:25] answer. Number one, my surgeries are being canceled. I do minimal during the COVID because all the nurses are deployed to COVID ward, but I think vaccination is important. I think everybody should get it if they can.
Dr. Tamer Seckin:
Well, in our hospital, we make sure there's a COVID test 48 hours prior to the procedure, and there're no visitors. There are strict guidelines. Even in private wards, they don't accept any visitors. So, our surgical schedule is moving on, but this is New York. It's not California. I do not know what tomorrow brings. So far, we are lucky. I'm sure Farr had also. I had my first vaccination and the second one. Second one made me sick for a day, but I feel lucky. I'm even embarrassed to say that I got mine because we do surgery. However, I think we have to protect patients and strict guidelines with distancing, and the mask is a must and will be strictly followed, I'm sure, in the next 100 days in New York or the rest of America.
Dr. Togas Tulandi:
Yeah. All patients before surgery should undergo COVID tests, and if it is positive, of course we cancel it, but everybody should have COVID tests the day before.
Dr. Tamer Seckin:
Thank you. I think we are getting close to our main speaker and the keynote speaker. I'm sure he is somewhere in the speakers room. We're looking for Arnaud Wattiez. I'd like to really run his video first, recorded video. Then, we will recognize him, or we should recognize him now, Harry. How do you say? How do we go?
Dr. Harry Reich:
Let's say hi to Arnaud. It'd be great to do.
Dr. Tamer Seckin:
I don't know. Is he there?
Dr. Arnaud Wattiez:
Hi, everybody. I am listening to you since a while.
Dr. Tamer Seckin:
Okay.
Dr. Harry Reich:
Hey. You're looking good.
Dr. Arnaud Wattiez:
Yeah.
Dr. Tamer Seckin:
Arnaud, before you came, we were talking about a lot of things and your name was there. We mentioned you, and this is a picture that I shared. I don't know if you guys see this. Do you see this picture?
Dr. Victor Gomel:
Yes.
Dr. Tamer Seckin:
This is [crosstalk 00:54:16]. This is Brussels 25 years ago. Harry says you look younger than anybody else, and he's talking to you, and you know everybody here. This is Brussels exactly 25 years ago or 23 years ago. Certainly, there's [Bruhan 00:54:33] on the right-hand side. Harry made sure I put this picture there so your memories will be alive. I have to introduce Arnaud as someone that I met very early. I regret very much when he was in Strasbourg, I never went there. But we did follow from a distance wonderful teaching, basically teaching a great surgical technique that he followed. I'm sure he also, like me, is affected by Dr. Reich. I know they were very good friends since then. I'd like Harry to take over and say a couple of words before we present this award to him, and we will listen to his presentation later.
Dr. Tamer Seckin:
Arnaud will be the recipient of the Harry Reich award simply because the foundation stands for the advancing, the science, and surgery of endometriosis. We believe surgery is the key treatment, whereas other things, all medications, are management. There is a difference in the role of surgery because of drug company policies and everything else cannot be put under the table. We want to bring it to the front and keep it there, but quality surgery, precision surgery, surgery based on tissue diagnosis, and leaving and removing as much as possible, but not too much. Arnaud talks about not removing too much and be careful about that, and wonderful other things. Harry, please take over.
Dr. Harry Reich:
Well, it's a great pleasure to both see and hear Arnaud. I met Arnaud in 1985 when I was looking for somebody else in the world who did laparoscopy. I heard about what they were doing in Claremont, Vermont, and I went there for a couple days and I saw the whole situation, the whole system. I saw how it evolved. I saw great surgeons. I saw Arnaud move to Strasbourg and become the leader in the world of endometriosis surgery, and now, I guess he's in a very famous place in Dubai with a new center. It's a great pleasure to see him here. We have a lot of memories and I don't want to discuss them too much, but I think we'd all be better served by Arnaud's talk, and I must say that I believe everything that he says.
Dr. Tamer Seckin:
We go to your presentation. I'd like to read this. The Endometriosis Foundation of America Harry Reich award for pioneering work in the science and treatment of endometriosis, Arnaud Wattiez. I'm sorry it reads March 14, 16, 2020. That's the way it is. I wanted to overnight this to you to Dubai, but I was warned that there could be delays and you may not be in your house, so this is it. I'm sure. Do you guys see this? It will be in Arnaud's hand this week. Thank you. Arnaud, would you like to say a couple things before we go for your presentation?
Dr. Arnaud Wattiez:
Yeah. First of all, I'm very honored by this award for many reasons. The first reason is the name of the award, which is Harry. As you say, Tamer, Harry marked my professional life, but also my personal life. As he said, we met in '85. At that time, I was more driver than a doctor, and I tried to entertain Harry under the direction of my boss, and I tried to make him safe in our very, very remote region in France. From that time, I remember that doesn't matter the place, doesn't matter the building, doesn't matter the technology. What is important, our people. Thanks to my start in this [inaudible 00:59:07] region, I still get the chance because I think that under the direction of our boss, Professor Bruhan, we did a good job and we were recognized worldwide. That's why I met Harry and I met also Cameron [Neisha 00:59:24] at this time. That definitely changed my career and helped me to work better and to understand better the needs of our patients. I'm very glad to have this award because Harry is behind this.
Dr. Arnaud Wattiez:
Harry, officially, I want to thank you for all you have done for me. You are one of my mentors, if not the most important mentor. In addition, you are a very good friend. With emotion, I thank you. As you say, we have incredible memories, and it's always a pleasure to share that. All the people in the panel here are all my friends and we've worked together since so long that we have also incredible memories. Tamer, thank you too for the Endometriosis Organization of America to award me this. I'm not sure I'm the guy who should get it, but I'm glad to get it, and that's it.
Dr. Arnaud Wattiez:
I was listening all your discussion, and I think this is not a closed story, so we have a lot of things to discuss which are a little bit, in my opinion, autonomic. If we speak about cancer and speaking about conservative surgeries a bit on genomics. We have to really be sure about the message we want to deliver, but surely I know that those patients need help. As you say, surgery is probably a part of their health, but should be done by profession. This is the aim of my message. Thank you again.
Dr. Arnaud Wattiez:
Good afternoon. It is a real honor for me to be here and to share with you some of my experience and finally, now that I've come to a certain age, some research about the management of deep endometriosis, and this is an honor also to have been nominated for this prize.
Arnaud Wattiez, MD:
They did for these, a price, that I will get today. So I will start, my talk, which is excision without mutilation. It is possible. I have quite a large experience, so I have no disclosure to declare on this talk. And you that I really feel that concerning endometriosis, the real progress would be to move from sick care to prevention. And this is all what we try to do with a better early diagnosis by imaging and we have done a lot of progress on this. The markers that can detect the disease even earlier, and then from these early [inaudible 01:02:55] diagnostic to make an early management that will avoid the surgery.
Arnaud Wattiez, MD:
So I know that this is a little bit strange from a surgeon to promote the non-surgery, but you know and we all know that what we see from the disease is like this picture, beautiful picture. The same part of the iceberg. And we can offer to our patients a lot. But the disease itself, it's obviously invading the quality of life of the patient. But also can play a role on the, let's say, the degradation of the wellbeing of the patient. So when you look at this and I like these articles to say that the damage may be due to the disease itself, but also to the surgery or to the surgeon. And so, I mean that, that's why it's very important to talk about the disease, the knowledge, the techniques, and also the training and the experience of the surgeon.
Arnaud Wattiez, MD:
So when we talk about treatments, we can balance. And I think from my knowledge this is the only disease where a patient with the same symptoms can go to see a medical doctor, an IVF doctor or surgeon, and she will get three different answers and proposal to treat the same disease. So I think that some point that we have to look at what we do and try to be a little bit more focused on the patient. So medical treatment has some side effects, is always contraceptive and probably just suppress the disease until the patient quit. And we have the problem of the compliance with the treatment from our patients. Surgically, we know this is aggressive, risk of complication, adhesion, et cetera.
Arnaud Wattiez, MD:
So what we know first is that endo and deep endo affect the quality of life of a patient. And lot of data, I share one with you, but we all have these experience that we have a patient that have tried lot of things, that come at the end to us. And if you take the general consideration that we deal with young patients and this disease is not a cancer. And most of the time as those patients are young, we speak about fertility preservation more than infertility, and we have the risk induced by surgery. So those are the main problem.
Arnaud Wattiez, MD:
And so this is not a cancer. I want to stress on that because, and this is really fitting with my talk, in cancer surgery, you can be very aggressive and you can also obtain some mutilation because at the end of the day this is life. But endometriosis surgery should not be compared to cancer surgery. And I will come back to this.
Arnaud Wattiez, MD:
And so, for example, we do not need clearly to obtain the optimal cytoreduction that we need to have for cancer, okay. And in the other hand, there is no safety margin. So to do a large resection for small nodule is not either recommended. And so we have to stop to say, "Oh, endometriosis surgery is exactly like cancer surgery" is not true. We go to the same space, we have to deal with the same organ, but we should not do the same. And so I think this is the first thing where we should not mutilate patients for endometriosis.
Arnaud Wattiez, MD:
And at the end of the day, we know that surgery well done is very efficient. And again, we have a lot of data, I share with you one, but we have much more data. And you see that coming from people and my data showed also that we are drastically reducing the pain when we do the surgery. So it means that we should do the surgery and probably not the first line therapy we have to indicate it. But when we come to surgery, we have to tell all the surgeon and tell all the [inaudible 01:07:19] surgeon means to be radical to the disease and to be strictly conservative to the function.
Arnaud Wattiez, MD:
And so, and above all, in this story of endo, we have to respect the patient requirements. Again, same article. So if we want to respect the requirement of the patient, is not enough to be on the right place at the right time, but you also have to be the right person. And so when I say, and this is the first message of these talks is, if we want to do a proper surgery without mutilation, we have to be the right person on face of the patient. And to be that we have to get the special training. So we have many problems to answer, should we operate or not? When we operate, if we do? How to operate, if we do? How we preserve the fertility and how we preserve the function.
Arnaud Wattiez, MD:
So the risk of operation is very well-known and it comes to the ovarian reserve. And you see here, for example, in this picture, the left ovary have been operated, the right not, and you see the difference. So we know that we are [inaudible 01:08:24] and we have to pay attention. We are also adhesion maker, and so adhesion provider and adhesion are not, neither for the function or the fertility. And so if you operate, you risk to provide adhesion.
Arnaud Wattiez, MD:
Now, if you do not operate, or if you are operate badly, you can come to full cul-de-sac occlusion or deterioration, et cetera. And so that can be due to the adhesion from the disease that we let going on, or it can be due to the adhesion provided by the surgeon. So this is also the risk. Now, if you do not operate, this is what can happen. And here this is a very young patient, 27, and you see the two big tubes masses on the side, right and left, are not the bowel, they are ureters. And so, this patient, we have to do an extensive surgery, bilateral re implantation and we just save only one kidney.
Arnaud Wattiez, MD:
So that means that we have to make decision. And when you come to young patient, we have always to say that probably we should not be too aggressive early. But also if we are not, we have this famous centralization of the pain and the pain is not in the head is in the brain, as we know. And so we probably have to reconsider the risk of [inaudible 01:09:48] of the pain. Before we say, no, we don't touch.
Arnaud Wattiez, MD:
And so, again, benign disease, young patients, fertility preservation. And for fertility preservation we have a lot of ART techniques and oocytes pick up and freeze them, frozen embryo, frozen ovarian tissue, [inaudible 01:10:07] in vitro maturation of immature follicle [inaudible 01:10:11]. But also we can discuss partial surgery, or better in my opinion, economical surgery. And this is the point.
Arnaud Wattiez, MD:
My point is we have a very challenging disease. My point is that it affects many organs. So I mean, that is not only the problem of the gynecologist, it's a problem of colorectal surgeon, it's a problem of the urologist. And I prefer myself to combine all those competence in one, like we do for oncology in gynecology. But you can also work in multi-disciplinary setting but it mean that you have to discuss, and the patients should see all surgeon that have to understand. So you have to deal with ovary, vagina, uterosacral ligament. But you have to deal with ureter, vessel, bowel and nerve.
Arnaud Wattiez, MD:
And so we have the challenge and the challenge is major postoperative complication. And I don't speak about fistula, bleeding, hematoma. I speak about bladder, bowel and sexual dysfunction post-op, or de novo adhesions that impair fertility. And so I think that we should not mutilate our patients. And when you come to mutilation is because we produce or we induce some dysfunction that will make that even if the patient is better in pain, if she cannot empty her bladder, this is a problem. And we have solutions so it means that we should probably not over treat patients and some have done. But we should also certainly not under treat patient, which is also opening the door to iterative surgery. And so that's why I say we have to be radical but economical.
Arnaud Wattiez, MD:
And you know that the period is very favorable to a lot of small phrase like this, that's why I promote make less be more. And I will give you two examples. And I think the way to non-mutilate our patient is to do the job, but making less damage by knowing better. And at the end, we do more for the patient. And so I give you two examples, I will give you the nerve and I will give you the bowel. I cannot do more because the time I have is too short.
Arnaud Wattiez, MD:
But if you remember that the nerve sparing concept have been developed in the early fifties, late fifties, by Japanese [inaudible 01:12:42] for preserving nerve in early cancer, where taking out some tissue for staging was important, leaving inside the nerve intact. And so unfortunately, and we have seen recently that a lot of surgeons start to dissect the nerve for endometriosis and develop concept like nerve sparing surgery for endometriosis. We have a problem here because what happened, we have seen a lot of useless dissection of nerve from the superior hypogastric plexus to the inferior hypogastric plexus with the reason that it damage the nerve.
Arnaud Wattiez, MD:
Or if you look this beautiful slide coming from the work of [inaudible 01:13:31] you see that when the nerve is involved by the disease, is intrinsically involved by the disease. And so when you see this picture, you understand immediately that this nerve is not dissected. And so what I want to show you also is this beautiful normal anatomic nerve. So two reflection, don't touch this nerve because you see the beautiful vascularization, the beautiful freedom of this nerve, being free under the [inaudible 01:14:02]. So this nerve, everyone, every single surgeon can dissect it. When it comes to endo, it become impossible. So you have two choice, either you cut the nerve, so you should answer the question, what happens if I cut, to this patient? Or you can let some disease behind, and this is not a cancer.
Arnaud Wattiez, MD:
And so, I mean that we have a lot of data on nerve dissection, and we know that this is very deleterious. So you mean that we have decreased the flow for value of 74 gram when you stretch. Imagine the force we apply with our instrument on these nerve when we dissect it in there. So to conclude with the nerve, there is no more nerve sparing surgery, that there is ureter sparing hysterectomy. So I mean that if the nerve are involved, we cannot dissect them. And we have to discuss if it works to remove and to be fully aggressive to this patient, or if we can let some disease behind. Obviously if the nerve is not involved, don't touch the nerve, but don't even dissect. So if the nerve sparing concept in endometriosis is to dissect all nerves, to see if they are involved, I think it's very deleterious.
Arnaud Wattiez, MD:
The second one example I want to give you and share with you is the bowel. Bowel endometriosis. So we know since very long, that the optimal treatment for endometriosis is excision. We know it for the peritoneum. We know it for the bladder. We know it for even the ovary. But we know that we have a [inaudible 01:15:45]. But only in bowel, we discuss a lot of functions. So we have the shaving, we have the disc resection, we have the [inaudible 01:15:55] section.
Arnaud Wattiez, MD:
And people are challenging. So most of the people say shaving is enough and this is probably true in some occasion, but we have to understand why. So we are gynecologists with less experience in bowel surgery and the colorectal surgeon have a poor knowledge of the disease and certainly no knowledge of the patient. So we have this problem and so we should solve it. So either we make, like in oncology, tumor board where everyone knows about the disease and knows about the surgery and knows about the patient desire, or we make transversal competencies to solve the problem.
Arnaud Wattiez, MD:
So I think that one statement, large total mesenteric excision for benign lesion are no more acceptable today. And I think that we should claim that. And this is very important. And so I mean, that is a gynecological input. You can do shaving, and I think that again this is [inaudible 01:17:03]. If you choose, there is no one that tell you that you should be in CCR0 like we say in oncology, and you can leave some disease behind. When you do a shaving you have to accept the fact that as it has been shown in the work of Tremorgram, if you do a shaving, you will probably let in more than 40% of the case, disease behind. This is acceptable, but you have to know that and you have to consider it.
Arnaud Wattiez, MD:
Now what we have done with gynecology... Here you see this is a bowel that has been removed 15 years ago. For a small nodule you remove 30 centimeter of the segment. Sorry, this is what we do today, we do that for this tumor, which is about 5.5 centimeter. We do a 5.5 resection. You see, we are exactly at the age of the tumor, and this is what we have done. And this is the gynae input on the matter. And how we did that, we look at this, so look the technique, shaving, discoid, segmental. And look, radicality vs function. So shaving, [inaudible 01:18:17] not radical at all, but function is better, is good. Discoid, more or less radical depending on the size, but function is still better. Segmental, radical and question mark what is the function?
Arnaud Wattiez, MD:
So if we can answer to that question mark, we have the solution. And the answer is not easy because obviously if we continue to make total mesenteric excision and with ileostomy with dissection of the left angle, I mean that the patient will pay the price with bowel dysfunction post-op. Now, if you know the anatomy and the technique, and I think this is not so [inaudible 01:18:56] when I was doing oncology, I was doing bowel resection. So now when I do endo, I also do bowel resection. But I understand that it's not possible, there are privileges, et cetera. So no problem, we can work on team, but we should still that you have three space, posteriorly to the right thumb, you have three space, determined by two fascia, the presacral fascia and the fascia propria of the rectum.
Arnaud Wattiez, MD:
So you have to presacral phase, the interfascial space and the [inaudible 01:19:32]. So when you do benign disease, what you do is you do a [inaudible 01:19:39] excision. So you dissect the rectum between the bowel wall, and the fascia propria the rectum. And it's not easy. And you will recognize if you don't that... Here you are between the fascia propria and the presacral fascia, look all the main branches of the nerves. Here you have the sacral root, you have the hypogastric nerve and you have the splanchnic pelvic nerve.
Arnaud Wattiez, MD:
And you understand that if you cut the sacral root, you are going to de-nerve all the segment that depends on that too. And now you understand that if you're on the transmesenteric plane, all the branches you will get are just for the segment you resect. So you understand that there is no damage post operatively.
Arnaud Wattiez, MD:
And I think that we have to conclude. So if we go to economical segmental resection, for example, they are effective, safe, and radical. So, I mean, we answer to the question of the patient, but in addition, they have the follow-up and they have associated with very low post-op dysfunction. So we understand that sigmoid [inaudible 01:20:46] and we can tailor what we do, more discoid and shaving on the rectum and more resection on the sigmoid. But this is what we have learned.
Arnaud Wattiez, MD:
So in conclusion, when I say we have a lot of challenges in young patient, and we should certainly not mutilate them because they have a long life in front of them and they need all their function to achieve their life with all these desire. So we have to replace the concept of radical surgery by economical. Economical doesn't mean to be less radical, we can be radical and economical, it just matter of knowledge and training. And then we have to develop these economical radicalism by these better knowledge of the disease, the patient requirements and the anatomy. And then we have to revisit the concept of nerve sparing because I think that it has been a deviation of the goals. So I mean that everyone now start to dissect the nerve for no reason, and I show you that the dissection is deleterious. And so we have really to try to focus on patient objective.
Arnaud Wattiez, MD:
And that's why endometrial disease is very interesting because as this is not a cancer, we should not behave like oncologists. And when I treat an ovarian cancer, I know that if I let one millimeter of the disease I will impair the life expectancy. And so I will not, but not in endo. In endo, if you have a patient with endometriosis and no symptom, you do not treat. And I think is... We don't want to have patient without endo, we want to have patient without symptoms of the endometriosis and disease [inaudible 01:22:44]. So we have really to develop these new subspecialty pelvic surgeon, endometriosis surgeon. I think that we have to address better the problem of our patients.
Arnaud Wattiez, MD:
And this is a slide that I love because I defend surgeons is very, very long. And I think that to be a surgeon, you have to get a lot of quality in image. I think creativity, curiosity, imagination, courage. I think your courage especially for endometriosis has to be really high. And you see that ability just a small part. So don't believe that you have to be [inaudible 01:23:24], you have to be knowledgeable. And from knowledge, you have to understand. And then from understanding, you will go to intuition. And so I think that this is very important.
Arnaud Wattiez, MD:
And we have to use all these quality to turn them to us, the patient problem and the patient objectives. And if we go there, I think we are going to treat our patient much better. So I think the concept to make less more is based on knowledge and training. And I think this is a very important concept that we have to develop. I know that surgeon have an ego, but sometime we have probably to put something on our ego and to serve better the patient.
Arnaud Wattiez, MD:
So, again, I thank you. I thank you for the honor. I thank you. I hope that I give you some flavor. We can discuss the ovary, we can discuss the bladder. We can discuss everything the same way. I think we are here to serve patient, and I hope that this is what my message deliver to you. Thank you very much.
Dr. Tamer Seckin:
Thank you, Dr Wattiez. Thank you very much. It's a great presentation. Certainly you are absolutely right. If the patients are asymptomatic, you shouldn't touch it. Certainly if there is no complaint from the diaphragm region, you don't need to go there and cause more problems certainly and other things. You also say that the real progress in endometriosis treatment would be to move from sick care to prevention through early diagnosis. Now you got to elaborate on that. Can you?
Arnaud Wattiez, MD:
Yeah. Yeah. It's obvious when you see the surgery, the problem... It's a vast discussion and Dan Martin is here and I know that he exchanged with me some emails sometime. And, for example, I thought to say, you have to respect the patient objectives. And we have to recognize that sometime those objective are either difficult to realize or to fulfill. And I just refer to one patient I operate three days ago, so very recently. And when I saw the patient, I told her, "Really what you need is an hysterectomy and probably bilateral oophorectomy because your situation is such that"... she was 43, she has kids. But she said, "No, no, I don't want my uterus removed. I don't want the bowel resected" et cetera. And so this is what Dan called probably the personal autonomy. And we have to respect the personal autonomy and understand that this is a philosophical discourse since the 17th and the 18th century.
Arnaud Wattiez, MD:
But in the other hand, this personal autonomy goes against the political autonomy, that we are facing nowadays. And so I obviously respect the patient desire, knowing that this is not good for her. And so I think that what would be better to not come to this dilemma, which is impossible to solve because honestly, to do something that you don't believe efficient is difficult for a surgeon, that we face sometimes this problems. And that's why I really think that to avoid this dilemma, which is not only philosophical, but human, I mean that we have to move a little bit ahead of this. And if we can obviously find a way to diagnose.
Arnaud Wattiez, MD:
And I know that now in Europe, it said that the time between the onset of the symptom and the diagnosis in nine years. I know that Dan will say 14 years in average. But I think that if we can make the diagnosis earlier, because endo starts one day and then grow and then become more severe. And so some patients stop earlier in their severity. Some patient goes more severe, but I think that if we may have probably this is more in the markers or in the genetics on the risk factor, and we may have a way to contain the development of the disease, obviously this is better. So I think it's a very trivial [inaudible 01:28:21]. I think that we can do a lot surgical-
Dr. Dan Martin:
[crosstalk 01:28:28].
Arnaud Wattiez, MD:
Yeah? We can do a lot surgically, but also there is thing we cannot do. There is a [inaudible 01:28:36] tube that you cannot repair. So I don't know if it answer your question.
Dr. Dan Martin:
Clarify your answer about early diagnosis, do you mean earlier surgery or earlier diagnosis using some non-surgical technique?
Arnaud Wattiez, MD:
I really feel earlier diagnosis not using any surgery. I really feel that we have, I don't know if it would be markers of the development of the disease, it will be genetics on the risk factor, et cetera. But it means that I really feel that we have to prevent the growth of the disease because as a surgeon, I do not feel that the problem is the disease itself. The problem is the reaction of the human tissue to the aggression of the disease that makes a problem. And so when we operate patient and we find these famous frozen pelvis and the frozen baby she's made for what? A little bit of disease and a lot of adhesion and fibrotic tissue and reaction of the surrounding organs. And that's it. So I mean that if we can notify a patient with risk and from this patient [inaudible 01:30:02] we treat the patient that will starve the disease. And if we find a way to contain it, I think really this is what we should do.
Arnaud Wattiez, MD:
So seek care is good, this is what we do. I am the seek care doctor, but I would like better for those patients. Honestly, again, what I say in my presentation is strange from a surgeon, to promote to not do surgery. But I think that this is really what we should do, because honestly speaking in some cases to be at the same time concerning the function and treating the disease is very challenging. And so probably if we be a little bit in front of that, it will be better.
Dr. Dan Martin:
Yes. You stated that 40% of patients after limited excision have residual endometriosis.
Arnaud Wattiez, MD:
Mm-hmm (affirmative).
Dr. Dan Martin:
There are patients' questions that are coming up about why would you leave that much endometriosis behind? And the corollary question is going to be, if a patient still has bowel symptoms, six to 12 months after the removal of a large nodule, what would you tell her about the probability of residual bowel disease and how it can be approached?
Arnaud Wattiez, MD:
Yeah. I know your question and this is an excellent question. So it start like this. So I mean that I know you speak about the [inaudible 01:31:30] work showing that you have micro-implants a distance of the big nodules, and this is true. But the first statement is to see if you have non-symptomatic endometriosis, no one treat it. And so, I mean that the small two millimeter implants or less probably has no clinical significant at the time, so.
Arnaud Wattiez, MD:
But that said, it could evolve and eventually could become symptomatic and I understand that. So I think that when you treat patients with endometriosis, whatever, bowel, bladder, ureter, whatever, I think we have to be prudent and to say, "Look, we cannot eradicate fully the disease. Because for those reasons we know that, first of all, if we want to remove all, probably we are going to affect your quality of life in term of function. And two, that probably there are lesion that we cannot see palpate or whatever. And so we are not going to be able to remove everything. And there is a small risk of recurrence of evolving of remaining disease." I think this is just a matter of discussion. What we want from the surgery is to bring back patient to a good quality of life, and doing so, and probably leaving the two millimeters...
Dr. Arnaud Wattiez:
By me leaving the two millimeter nodule far away from the big nodule I show you will not affect your life. And to be honest with you and to come to the end, because I knew about this question and I look in my follow-up, honestly, I never have seen a recurrence after bowel resection in my [inaudible 01:33:27]. So it means that probably we have left behind some nodule or micro nodule at distant, but they never expressed clinically anything from... Honestly speaking, some of my patients who have gone and [inaudible 01:33:45] of treatment, but it's not totally true because most of the patients are very, very keen to come back to you. But in my experience, I have seen recurrence after shaving, and that I have seen a lot. And I have a re-operate patient after shaving to do bowel resection, that happened. But I never have redo a bowel resection after a bowel resection.
Dr. Arnaud Wattiez:
But it's imperfect. You know, from your discussion before about the risk of cancer, so now you can ask even the question if this is correct to let an micro nodule because it's less than three centimeters.
Dr. Dan Martin:
Yes.
Dr. Tamer Seckin:
Thank you. Thank you, Arnaud. I can't agree more. I personally did not have any recurrence of bowel after bowel resection, too. However, due to fibrosis maybe, some pain comes back even though you look back, you don't see anything but fibrosis, most of the time. The question really is, is not what we feel and what we remove as masses, but the challenge of peritoneal endometriosis. As much as it is dismissed, peritoneal endometriosis really represents significant percent of the patients who have endo and their complaints that has no imaging techniques or no other test other than patients history and pelvic exam, highly suggestive. So when you go back, obviously in general, there's with these cases, there's a high rate of recurrence compared to others.
Dr. Tamer Seckin:
So, when you really say that we have to detect early, yes. But then how do you approach it? I think the audience would like to hear when patients are symptomatic and you don't want a surgery, what's your first line of approach. I, in my practice, [inaudible 01:35:57] this and that. So basically suppression of the ovulation and periods. But when do you think that's the optimal to intervene? Obviously the patient has the autonomy, and I think you also pay attention to symptom directed approach. I like to hear your sentiment on this, if you can.
Dr. Arnaud Wattiez:
Yeah. I mean, this is exactly the challenge with endo in young patient, for two reason. One, because as you say, the problem is the time to intervene. And this is difficult, but I think this is not the most difficult thing. The most difficult thing is that those young patients would like to be pregnant when they will desire it, which is not now. I mean, this is really the fertility preservation. And fertility preservation and early management, early surgical management, sometime are antagonists. And so that's why we all are hesitating to do surgery on young patients. So I think in my opinion, like you, if I have a patient with pain, mainly because it's a main symptom, and I don't speak about the dysmenorrhea of the young lady, but really abnormal dysmenorrhea and pain, which is not supported by a clear imaging of endometriosis.
Dr. Arnaud Wattiez:
Like you, my first line therapy is medical. With medical whatever you want, OCP, progestin, whatever you want, more OCP. But let's say this is a suppression of the ovulation and suppression of the period in kind of dysmenorrhea and that this is classical. Now the problem is when you have a young patient with those symptoms, which are supported by your clear imaging of deep endometriosis. And this is where, in my opinion, the problem starts. Because then now, you have a young patient with clear endo in imaging, clear deep endo, and fertility preservation. And you have the problem of the ovary, but you also have the prime of these deep endometriosis. And so I think that as I told in my talk so that we have a lot of questions. The first question is, okay, do surgery remove, the deep endo, leave behind some addition. What about the fair TDT, et cetera. [inaudible 01:38:47] vision oversights, retrieval. That all can be discussed. And in the opposite, if you manage it medically and you are not efficient, you have the risk of the colonization of the pain.
Dr. Arnaud Wattiez:
And so that's why the discussion on the young patients should be really here case by case. And as you, I think the highest number of patients I see are patients that already tried a lot of treatment and are still with the pain. And I think that when the pain become invariable, become untreatable medically, it's time to do surgery. Even if you are young.
Dr. Tamer Seckin:
Thank you, thank you. We'd like to move on, but this question is important. I want Victor Gomel's pitch on this question. Actually, it's directed to Zupi about uterine surgery. I'm sure I know where you are. Uterine preservation for fertility is a big deal. And as we discover more and more diagnosed adenomyosis with extensive use of MRI, they're reading more and more adenomyosis. When they're small, no problem. But when there's a diffuser there now, I mean surgery, you can do the surgery, but there's a limit what you can say and promise. I want to hear your experience. And Victor, please, the question is about really like this.
Dr. Tamer Seckin:
Thank you for this information regarding adenomyosis. One treatment option I did not hear mentioned is the Osada procedure for diffuse adenomyosis. This process is rarely done, especially outside of Japan where it was developed, and where the majority of adenomyosis surgery are performed. Why do you believe this procedure is so uncommonly done? And do you believe it is worthwhile for endometriosis adenomyosis specialists to learn how to do this procedure in order to offer patients with diffused adenomyosis more treatment option than conserve the uterus for pregnancy? Well, who's willing to ask. Victor.
Dr. Victor Gomel:
Osada is a friend of mine. I actually did in Japan a microsurgical course in 1981. So he was there. And then, you know, we've been together. When he was doing the article to publish his technique, I couldn't understand the writing. So I was in Japan, I went to Japan, and he showed me several videos and I understood why and how the procedure was being done, and I helped him actually with the article. So this procedure he does, he's a very good surgeon, first of all. And he also, because you see microsurgery was not created to use small instruments. Microsurgery was too hard to decrease lesions. And I can tell you about that tomorrow, because today we don't have much time. So the Osada procedure is done when there is extensive adenomyosis. And to be able to keep the patients with some sort of good wall of the uterus and give them the possibility to have a pregnancy with that uterus. So it's not for smaller lesions or confined lesions. It's for extreme adenomyosis.
Dr. Arnaud Wattiez:
May I comment on that?
Dr. Victor Gomel:
Yes, yes, yes. By all means.
Dr. Arnaud Wattiez:
Yeah. Victor, I agree with the Osada technique. First of all, I want to say that when we did with, as you say, diffuse adenomyosis, no focal, no whatever. And then it comes to a resection. What we observe when we do the Osada technique of the endodontic technique we have, that we have an excellent result on symptoms. Pain and bleeding. And that is totally correct. And we have patients that are, at least for the few years after surgery, happy because they have a normal life. When it comes to pregnancy, I want to be a little bit more prudent, because what we have observed is that, one, the risk of rupture is much higher compared to myomectomy. And two, is much earlier compared to myomectomy in the pregnancy life. And so it's said that myomectomy, the highest peak of rupture is 32 weeks. In adenomyosis surgical treatment, it seems to be 25, 26 weeks. And so I want to say that we are lacking data. And on my knowledge, one of a randomized trial on the Osada technique has been stopped for bad result obstetrical reasons. And so-
Dr. Victor Gomel:
Yeah. Right. And actually, the number of pregnancies he had after, you know, in the publication, you can see that we're very limited.
Dr. Arnaud Wattiez:
I do not agree, Victor, because they publish 40% of pregnancy. So it's not limited.
Dr. Victor Gomel:
Limited going to term.
Dr. Arnaud Wattiez:
Yeah. But I want to say that adenomyosis, the surgical treatment of adenomyosis, is like endo. It's very challenging. In one way, it's very... You want to do it-
Dr. Victor Gomel:
In my opinion, it's much, much more with extreme adenomyosis, is much more challenging than even sometimes endometriosis. Because you don't know what to do. You are shaving, taking tissue.
Dr. Arnaud Wattiez:
No, but really, I want to say the little RQ is quite optimistic. I think we have to be a little bit prudent, and I would suggest that these kind of surgeries really follow very closely, because I'm not sure that the results are so good in term of obstetric surgical outcome.
Dr. Victor Gomel:
No, no, I agree with you on that, because you are effectively destroying even the shape of the uterus. This is evident. But we have to gain other means to use pregnancy places that it's permitted. I have been very interested with the uterus...
Dr. Tamer Seckin:
Victor.
Dr. Victor Gomel:
Yeah. And, you know, I have even written an article on it. So sometimes, instead of doing a uterus from other person, which is a terrible operation. It is better to have a person we undertake that surgery to be the donor to carry the pregnancy. It's easier, and that's risky.
Dr. Tamer Seckin:
Thank you. Thank you, Victor. Thank you so much. I am sure the audience was pleased with these answers. My take on adenomyosis, I do hesitate. I have done the procedure. There are patients who still want it, but not for uterine preservation. They are adamant, fine. But however, there is no guarantee of the obstetrical integrity, as you say, the rate is there.
Dr. Victor Gomel:
Absolutely. Absolutely.
Dr. Tamer Seckin:
So gentlemen, we have to move on. We have one more session, but we will not be late. Dr. Possover and Dr. Usta and Dr. Ie-Ming Shih's section, which designates our commitment for the neuropathies and neuropathy surgeries, and the molecular level of adenomyosis and peritoneal endometriosis. Unfortunately, Possover has a problem. He promised he would be online, he's not. His video is online. I watched it, it's terrific, very nice as usual. And he says, basically, pelvic pain can persist following endometriosis surgery due to neuropathy and cause of number of symptoms, and he really goes over all the symptoms. And understanding the cause of pelvic pain following an endometriosis surgery to offer patients the right diagnosis and treatment. That's where the neurosurgery comes, he says. Listening to the patient and carefully reviewing their medical history is essential to understand their pain. I don't think anybody disagrees. Please go to our database in the foundation. You can load this video and watch it at your convenience. Let us know if you have any problem.
Dr. Tamer Seckin:
Second talk was given by Dr. Usta. He's a young surgical talent from Istanbul, Turkey. I was very, very impressed with his presentation. He has given four cases. Basically, most of them on vascular entrapment of the nerves, which is rare, but he declares that it is an important cause of pelvic pain. You have the right MRI people reading that, obviously. Concerning that pelvis is an anatomically complex area, this part of the pelvis is rarely taught. It's a real tiger zone and difficult to navigate, which we all agree.
Dr. Tamer Seckin:
We are lucky to have Dr. Ie-Ming Shih online with us. You see here? Dr. Shih?
Ie-Ming Shih, MD, PhD:
Hi. Could you hear me?
Dr. Tamer Seckin:
Yes, I do. So let me introduce you, Dr. Shih. Dr. Shih is the TeLinde Professor of Pathology at John Hopkins University. Shih works with Dr. Ihon, who is the pathology at Osaka and also John Hopkins. He has written multiple articles at the molecular level. In fact, we have an article that was published in the new England Journal of Medicine with respect to malignant mutation and otherwise benign endometriosis lesion. This article was game changer and has been getting a lot of positive response still. Dr. Shih, would you just basically summarize what you did make your talk about? I know pathology of adenomyosis are unique on non-malignant GYN disease, but tell us more. How do you achieve this much of research, and then what is your root of interest? Where do you think things are going with these research? Monoclonality? When does monoclonality of the endometriosis changes, and what is the practical value for future? Maybe I asked too many questions, but that's all I want to ask. Thank you.
Ie-Ming Shih, MD, PhD:
Thank you very much. It's a great pleasure to be online and to participate in this symposium. So basically, our laboratory and our research team at Johns Hopkins is very interested in where are these adenomyosis and endometriosis coming from, in terms of their ancestors. So, as you know, our laboratory is basically a molecular genetic laboratory in studying gynecology cancer. So [inaudible 01:52:17] several years ago, we are already inspired by this endometriosis foundation and also many colleagues in the field. So we think one more depression in endometriosis, how can we apply cancer research tools in order to understand adenomyosis and endometriosis. So as a result, we collaborate with many colleagues in the field, including Dr. Seckin. And so we tried to understand what's the mutation profiles in a genome-wide label. And how can this new research data help us to understand the origin.
Ie-Ming Shih, MD, PhD:
So as a result, we include several deep endometriosis, and nowadays we include adenomyosis and the peritoneal endometriosis alike. So we use a laser capture microdissection, which is a machine that we can isolate, and it reached epithelial cells or the stromal cells following individual lesions. From there, very minute lesions. We can purify the DNA and we can perform a mutation analysis to analyze 22,000 genes in the human genomes. And at the same time, can also profile epigenetics. They are [inaudible 01:53:52] in these lesions. So basically, briefly, if your genetic is the modification of the DNA is not inherited, it's not like a mutation, but it has a very powerful effect on gene expression and other biological functions. Okay. So based on analysis on somatic mutation, and we try to infer the [inaudible 01:54:15], just like a family tree. And to compare the eutopic endometrium and adenomyosis endometrium, and also peritoneal endometrium, likewise. And we can show their relationship is really complicated.
Ie-Ming Shih, MD, PhD:
So in my talk, I try to deliberate that, the detailed results. But the upshot is, the adenomyosis and the endometriosis, the epithelial cells, basically they can be traced back to their eutopic endometrium. So that means that adenomyosis and the endometriosis are related to the eutopic counterparts from the same patients. And why this is interesting is because about one or two years ago, Dr. Moore group published in nature, their group using this very similar technique to isolate normal endometrium in the uterus. And then they amazingly, what they found is on the normal individual endometrial glands, also harbor this cancer driver mutations. Like [inaudible 01:55:34] , and et cetera. So that means that adenomyosis and endometriosis harbor the mutation, can also be formed in the eutopic normal endometrium. So what that tell us is one thing: very, very clearly that adenomyosis and endometriosis rise from the eutopic endometrium at some time point during the productive cycles, but we don't know when. But at least they are several years from the symptoms arise.
Ie-Ming Shih, MD, PhD:
And based on the mathematical modeling and estimation, we now know that probably, the first mutation hit occurs in right after the puberty. So that means that the ancestors of endometriosis and adenomyosis actually develop many years ago from the symptoms start to appear. And also we are pri-epigenetics, which is the first kind of this kind of research. And we found that actually the methylation profile are very similar among these adenomyosis and endometriosis lesions among women. But there are certain profiles that are different that can be distinguished from the normal endometrium. So that can become a biomarker in official for early detection, as we just discussed previously.
Ie-Ming Shih, MD, PhD:
So our lab is going to harness this new genetic and epigenetic biomarkers to develop something that we can use for the early detection, like using the blood or in the cervical [inaudible 01:57:28], and et cetera, in order to identify the biomarkers in a eutopic endometrium or in a circulating blood, that we can have a risk prediction model for those women who have a higher risk to develop adenomyosis and endometriosis. And that is the supply we are working on in our laboratory, and it's by no means is a straightforward and easy job. I think our interest and that devotion is to make this progress in the coming years to develop some markers that we can rely on to help those women for the early diagnosis in these terrible diseases. And that's the summary of our research. And okay, thank you very much for EFA's support in the past several years.
Dr. Tamer Seckin:
Thanks, thank you very much, Dr. Shih. Don Martin, Dr. Martin, do you have any specific questions that we could-
Dr. Dan Martin:
Yes. There's a question here about transmission between mothers and daughters. Have you analyzed the transmission between mothers and daughters of mutations or epigenetic changes, or do you anticipate that epigenetic changes will be inheritable in this situation?
Ie-Ming Shih, MD, PhD:
Yeah, I think that's a very good question from the audience. I think this is really question the answer that everybody want to know, right? The familiar endometriosis or adenomyosis symptom. We don't know whether what's the profile yet. But I think, to my personal opinion, that inherited trait may exist in certain women, but we still don't know what's the transmission trait. So I would like to say every human disease coming from two parts. What is genetic, what is acquired. So adenomyosis and endometriosis are no exceptions. And the reason is, we have not done this yet because we are still in the early phase to elicit that, to reconstruct that genetic epigenetic landscape of the lesions. So once we have those data in mind, the next step is to understand their inheritance trait and what kind of the germline mutations or any mutation acquired in uteri can further facilitate or increase the risk of the women to develop adenomyosis and endometriosis. So the short answer is, that's a good question, but that will be in the future endeavor.
Dr. Tamer Seckin:
I think we are at the end of our time. I do respect people's weekend schedule. This session will be continued tomorrow. Dr. Shih, I don't have any specific question to you, but [inaudible 02:00:39] couldn't be with us because it's three or two o'clock, early in the morning in Japan. But I am so happy, and please thank you for joining us. I know you drove from Washington to New York. Hopefully not running away from the mayhem there. Well, we are really happy and we are humbled and honored for you joining us. To all speakers, Dr. Gomel, Dr. Martin, Dr. Rich. And Dr. Nezhat and Tulandi, which I couldn't say bye-bye. And Wattiez, thank you very much. We're looking forward to see you tomorrow at 11 o'clock for our fertility panels. Thank you very much.
Dr. Dan Martin:
Thank you, Dr. Shih. For all of the patients who had questions on the line that have not been answered, we will try to answer as many of those as possible, but we will do that by email. Thank you.
Ie-Ming Shih, MD, PhD:
Okay, that's very good. Thank you, then. See you, bye-bye.
Dr. Dan Martin:
Thank you.
Dr. Tamer Seckin:
Thank you.
