In the beginning what I would like to do is thank the people who are not on the program, Lone Hummelshøj for all the work she did in the background that most of you will never recognize, Christine Handley and Alex Garry for all the help they gave me by email in setting up the program.
There are no conflicts of interest on this one.
This is an illustration commissioned by the New York Times for Katy McLaughlin's article "Our Relationship Thrives on Missions". The purpose of this was to demonstrate how a couple cooperated together and worked better together if they looked at a project together and worked on that project. But when this was republished in the Memphis paper it came out in black and white. How many of you see in that picture what I saw in that picture? It completely throws me off as far as the article because I do not see that. I do not see it as a cooperative picture I see it as this one - we jump straight to it. If you look at the black images it is faces, it you look at the white image it is a vase. I see perceptual differences between the couple. I had to read the article twice to catch on to what it said. Perception gets in the way. Associations, previous associations, things we think we know, interfere with what we are doing.
The Industrial Revolution from 1760 to 1820/1840, depends on which version you believe, is over. At the end of the revolution do we have anesthesia machines? No. Do we wash our hands? No. Do we have Listerine? Has Joseph Lister come around yet? Not yet. We sure do not have hysterectomies. We are nowhere close to laparoscopies and Robbie the Robot is not around. So we begin about 1842 with anesthesia. We do not have effective anesthesia until 1842. We have Oliver Wendell Holmes who predisposes Ignaz Semmelweis in publishing "Puerperal Sepsis and Problems with Puerperal Fever". But Oliver Wendell Holmes, we do not catch onto the fact that he is part of this paper, why? Because he developed a career as a poet and father of a Supreme Court Justice. We know him, not as a physician, but as a writer and as a father of our country.
On the other hand Semmelweis does not understand that he is not Don Quixote, Curt Simms or any of those other people who fight the institution. He knows he is right, he is going to prove it and he goes down in history as losing the fight, which comes up later by 1862. So ten, 20 years later Louis Pasteur finally realizes we have bacteria and now we get Joseph Lister in 1867 who begins to use carbolic acid in surgery.
All of this results in an explosion of surgery. We get Walter Burnham from the 6th Massachusetts - you have to remember, for those of us who are from Georgia the 6th Massachusetts is okay. They did not burn Atlanta and march to the sea. For those of us from Georgia, we have a completely different view of history than the rest of you. The purpose of the Civil War was so Shermann could burn Atlanta and march to the sea so that Margaret Mitchum could write "Gone With the Wind" so that Vivien Leigh could get the academy award. It is all about Vivien Leigh! Okay? In 1853 he operates on the first woman to survive a hysterectomy. The story goes he thought he was removing an ovary tumor. She threw up on the operating table, pushed the ureter aside and he could not get it back in so he gave her a hysterectomy. She survived. Ten years earlier in England the patient did not.
Then we come to Rokinstansky. Rokinstansky is doing anatomic pathology. He is doing autopsies. We lost a lot of his work in endometriosis because he did not call it endometriosis, he called it cystosarcoma and other terms, it sounded like cancer. Ivo Brosens does not even believe he is going to talk about endometriosis because Evo thinks he thinks it is a cancer and Evo knows it is not a cancer. Ivo wants the one who first described the flowing nature who is called Cullen. Most of us go past Rokinstansky into the terminology he used. The first four are Rokinstansky's terms, the second ones are 1860 to 1920 and then we get into endometriosis and all those other things that come from John Sampson.
If we look at normal anatomy, to remind everybody what I am really talking about, the uterus is in the front, the cervix is hidden on this mucus, uterus is tilted back but it is up behind there. Uterosacral ligaments on either side, rectum down low, remember the rectum is basically retroperitoneal. When you look below if it is retroperitoneal it is rectum. If it has a mesentery it is sigmoid and then the sigmoid colon. In between all of that is the Pouch of Douglas. The Pouch of Douglas goes on to the middle third of the vagina in 93 percent of women. If it did not do that the posterior colpotomy on a vaginal hysterectomy would go into the bowel. For those of you who have done vaginal hysterectomies you know that is true otherwise you could just do a posterior colpotomy with the degree of ease that it is. Right behind that is the rectum. If we draw a line across the middle of the cul-de-sac we can pretty much assume that anything above that line, which is anterior, is going to be either vagina or cervix. Behind that line is going to be rectum. We do not want to operate posterior to that line unless you mean to be close to the bowel. Then way back behind us is the sigmoid. You can tell the difference between the rectum and sigmoid because the rectum is basically retroperitoneal, sigmoid is intraperitoneal with a mesentery.
Most of the talks we have been hearing in the last day or two have been deep infiltration with complete rectovaginal obliteration like this. Remember the previous thing we had a cul-de-sac. This one, the uterus is up front, cervix is behind it, rectum is right there, uterosacrals on either side and that is just flat as a board, the cul-de-sac is gone. In between it is the endometriosis. So this is basically obliterated disease. This is what I was trained on, this is what everybody in my generation was trained on. It is what we learned from Cullen in 1917. Before Cullen was Firth. The Firth publication is in Lockyer's textbook in 1917. Cullen, in 1917 Lockyer; all of them were contemporaries, these are the guys from whom we get most of our surgical understanding from.
If you notice on all of those pictures the vagina is below the lesion. We will come back to that in a second because it has to do with the mis-education we all have. The endometriosis in the first one is basically rectal-corporal. This is a lesion extending from the bowel to the whole back of the uterus. It goes way past rectovaginal. It is one of the tougher things to handle.
Now, if we look at two other Cullen illustrations from 1917; on the first one we have the cervix right there, rectum behind it, vagina underneath that, the lesion in between and what is missing from the illustration that he says is there? The septum, it is off the picture. It is nowhere close in spite of the fact that he wants to say this is rectovaginal septum endometriosis. The septum is way down below that. To make it even more obvious he calls this one rectovaginal, and if you look at that, above that is what? The vagina and the cervix. Below that is what? The rectum, except in this picture it has got a mesentery so it is sigmoid arising from where it should not be arising from. But that is rectum in the normal situation.
Then we go back to illustrations we have seen. If we look at my paper in 1988 and Anaf in 2001 we both had a picture that was very similar to Adamyan's picture and the other pictures. We draw the septum occurring right behind the cervix. I think that is rectovaginal. Leila Adamyan in 1993 published a retrocervical staging system that changes some of that. For those of you who do not know Leila this is Assia Stepanian's mother, Assia SurgeryU. SurgeryU which is now run by the AAGL, this is her mother in Moscow. So she publishes a retrocervical stage where stage one is retrocervical or vagina with no vaginal involvement. This is the reason Anaf and I were able to do what we did laparoscopically and that is core those lesions straight through the vagina without ever touching the rectum. In stage one and two you have retrocervical involvement, vaginal involvement but no rectal involvement. She has still got the same error I got. If you look she is drawing stage one with the cul-de-sac that is behind the cervix. This thing is supposed to be down in the middle third of the vagina, it is not supposed to be that high. So that illustration is off.
Philippe Koninckx and I made the same error. We drew our infiltrating type above there. We drew our retracting type and then the one that we were not really sure, adenomyosis - in all of these we have the septum in the wrong place. If you look at Philippe's paper or Philippe's illustration remember this is the one that is an invisible area of endometriosis. This is a nodule, it is easy to feel in the office the thing is 1.5 cm in size but you cannot see it. This is one of those lesions that after you dissect it you see the lesion right there, easy to see once you have it dissected out but until it is dissected you cannot see it. Surrounding that is the healthy fat. As you have heard in the last two days fat is our friend. We like operating in fat. But the rectum drops away from it. We are okay when you look at the lesions themselves, there are healthy fats surrounding it. About 85 percent of the lesion is fibromuscular scar. There is a fibromuscular metaplasia that happens as a response to the infiltrating endometriosis. I use the word infiltrating because I mean it. This is not a non-infiltrating lesion like a fibroid, which is an expansile lesion. This does not have a cleavage plane around it. You hope you can find where the planes end and where they do not. If this were expansile there would be a cleavage plane around it. This is infiltrating. The glands and stroma and recent bleeding, the little red dots, and old hemorrhage is the black.
So now we come up to Kuhn in 1982 and Vercellini in 2000 and Ron Batt and I in 2001; finally we catch onto the fact, Kuhn called it in 1982. The rest of us are slower. The vagina extends to the middle third of the vagina in 93 percent of patients. I finally get stage one right with the cul-de-sac below it so the cul-de-sac and the septum are low. Stage two is there with the septum right there. What is wrong with that picture that the Japanese do not like? The septum is not in that last position.
We have this as the original, the cul-de-sac is that yellow area, the septum is the blue area and we thought that it stretched, when you have the deep rectovaginal thing that would stretch the septum out and pull it with this. Now that was a postulate. We guessed that. We had no real data for that, we did not have observations. We were there we thought that was the septum but the Japanese told us it was not. The septum is really still right there. If you look at their pictures, which they have really good MRIs for, there is the lesion, that is still the septum right where it has always been - it has not stretched at all and what fills in is loose connective tissue. When these things stretch up on the Japanese thing we did not stretch the septum we fractured it. It fractures off the septum, pulls up, leaves you loose connective tissue behind.
Finally, to John Sampson, for whom we owe most of what we do today. All the rest was preliminary. Most of us give him credit for really inventing and coming up with what we said. Joseph Megs in 1926 called John Sampson the discoverer of endometriosis. What was John Sampson's response? No way, Pick did it in 1905, Rokinstansky did it in 1860. Although we give Sampson a lot of credit Sampson would have credited Pick in 1905 and Rokinstansky in 1860. Everybody builds on everybody else. Everybody looks at things and has to come along with additional information. But what he did do was look at endometriosis almost the same way we look at it today - with very little difference. He would take pictures like that and he would see chocolate cysts, blebs and infiltrations. All those lesions that we see today were published in the 1920s. We have become a little more sophisticated than him but we have not really added much to what he said.
John Fallon in 1950 talks about those little, clear blebs, amenorrheic endometriosis is what he called them - endometriosis that has not bled. Karl Karnaky by 1969 talked about transitions from water blisters to dark scarred lesions. He said it took over ten years, so these are all slow transitions. All this data really predates what we did. Those of you who have read my 1980s articles you realize that by 1988 I am up to 20 different descriptor types. If you look at the very last one, it is still other. I still cannot figure out what to call them.
The ASRM comes in in 1996 and as we talked about yesterday when they published this everybody came to the conclusion that all these types are endometriosis. Remember, none of these types are always endometriosis. Dark scarred lesions, the first laparoscopy can be wrong and the second laparoscopy can be really wrong because...buddy kicks in. But, those were my pictures so I do have to take responsibility for them.
From the talks yesterday we talked about powder burns. Remember the first one was a dark scarred lesion where the dark part inside is the old trapped blood. The second one, the vesicals are the endometriosis, the brown is hemosiderin and iron.
For those of you who were here yesterday what I want to try to do is, we talked yesterday about which one do you think it is, today, we want to take it one step further, which one do you think it should be? What I want to know is, is the powder burn A only, B only, either one, neither one and I have confused you anyway. How many of you in this day and time would say that it has to be A - two. How many would say it has to be B - one. How many of you think it can be either one - one or two or three...a whole bunch...10, 11 12. And neither? Who wants neither? We have a couple of neithers and powder burn is something else. Remember, we have terminology that we do not even have any good definitions for, we just use these things.
What David Redwine did in 1988 and Ken Sinervo, Bob Albee and Fisher did in 2008 was that they did not worry about all my 20 descriptors, they went to "if it is visually normal peritoneum then it is okay. But if it is visually abnormal it is not". In that classification and that definition they talked about smooth, non-disturbed peritoneum with no fibrosis and no scarring. The vessels were normal there was no neo-vascularity, no radiating vessels, nothing aimed at a target tissue. The peritoneum was transparent and there was no color contrast. There was nothing coming through it that interfered with your light. There were no cysts, no sub-peritoneal cysts, nothing that looked like an abnormal event below the peritoneum. There was no surface or sub-peritoneal fibrosis.
Probably the only study that I know in the literature that even begins to look like STARD is they published the one on Laparoscopic Appearances in 2008. In that study appearances that did not have a specific classification but had an abnormal appearance they found endometriosis in 24.3 percent of those. If you remember from my talk yesterday we talked about I had a 15 percent false negative rate, this is the same thing I am talking about. I trust their number more than mine because theirs was prospectively determined by criteria and mine just happened to me. If you look at this I have a 15 percent false negative rate and the question would be is if I followed their criteria, and get 24 percent here, would I still have a false negative, right, because I would have classified things otherwise. If you are not getting a false negative rate and you are not biopsying things that you think are not endometriosis that turn out to be endometriosis then you are missing things.
If you are doing biopsies and the pathologist tells you it is cancer and you believe it is endometriosis we have a major problem. If the pathologist calls it cancer it is cancer. Now, when pathologists call it non-specific inflammation, lymphoid aggregates, sub-peritoneal cysts, endosalpingiosis, psammoma bodies, those kinds of things, then I will leave it up to you what you do, I am going to believe the pathologist. If that is what they call it that is what they call it.
I kind of think the pimple model is the best model for all of this stuff and looking at a pimple we can look and tell somebody what looks bad. We cannot tell them what hurts - they come and go. They have their own patterns. Some go away by themselves, some need medication, and dermabrasion is sometimes used. The pimple model is the one I like for most of this stuff.
We will talk about theories just because we have heard Harry talk about theories and I have pulled some slides. These are all the theories that I generally talk about. If you notice about two thirds of the way down the list we have Mullerianosis I, II and III. If you do not understand Mullerianosis I, II and III it is difficult to even talk about Mullerian theory. One is embryonic rest, two is hamartoma formation, which probably does not come in, that is more like having a fibroid in the uterus, and three is choristoma, which means it is outward it does not belong but we do not understand why.
If you look at retrograde theory, remember retrograde theory says initiating of the event is desquamation of epithelium. From the endometrium it goes retrograde through the tubes, it disperses into the peritoneum, disperses through the abdomen, attaches to the peritoneum and then, to become endometriosis it infiltrates and grows. If we believe Ivo Brosens it has to grow to a certain depth or we should not call it endometriosis. He does not believe we should call these little superficial blisters endometriosis for reasons that are obvious to him but that are not obvious to me.
The timeline for that initial attachment takes anywhere from one to 24 hours in the lab. Dark, scarred lesions take four to seven years to develop and large nodules are anywhere from four to 20 years to develop. These things do not come up very fast. Attachment, infiltration and growth, to be able to do all this stuff we have to have a failure to clear the cells. The body's natural response to endometrium in the peritoneum is to clear it. It probably does that quite effectively 85/99 percent of the time. When it does not, then it can grow and it does not clear out maybe decreased apoptosis the programmed cell death does not always occur. There is an altered immune response, some sort of peritoneal inflammatory response whether it is a retrograde menstruation that is initiating the event, primary peritonitis, sexually transmitted diseases, something that irritates the pelvis, or an abnormal autoimmune profile. What I need to do is work all that genetic stuff in that we heard in the previous talk into this because it belongs in there somewhere. The last is an age dependent immunity development. Teenagers do not clear it as fast as adults clear it.
Retrograde menstruation goes back into the pelvis and once you are into the pelvis that is the diaphragm. Ready access to all the bowel, the appendix, diaphragm and the lungs; it can infiltrate into the sciatic nerve so you give me anything in the pelvis, bowel, bladder, appendix, vagina, sciatic nerve, diaphragm, lungs. I could explain on retrograde menstruation theory. I cannot use Mullerian to pick up anything but the pelvis. Mullerian is in the pelvis, it is not in any of those other areas. The only way you can get Mullerian to go into the pelvis is desquamation has to come from the endometriosis in the pelvis and then disperse and attach elsewhere. It is an aberrant form of Sampson's Theory.
If you look at that we get endometriosis on the diaphragm that can directly infiltrate into the lower lung fields, or, we get all those little foramen in that we think are responsible for ovarian pulmonary metastasis. Any of those cause that to happen.
Theories, I need Sampson and then I need a few other theories. For surgical scar I have to have direct implantation. I have to have immune competence and development of immune competence so I can explain differences between where it is in teenagers and where it is in adults. The induction theory because of Marsh and Lawford's paper because of Cabana's paper, those look like induction. Then boy we get off to the distal sites, eyes and spinal column. We either use Mullerianosis III, which is choristoma formation and that basically says it is there and we do not know why it is there, it just is; or, we have to use lymphatic spread/hematogenous spread or something along that line. You cannot use standard Mullerian theory because those are not Mullerian organs.
That was too fast to conclusion, wasn't it? In conclusion, some of these are new slides I was not quite sure of the timing, we will have time to ask questions...in conclusion, as we know from M.C. Escher not everything we look at and think we see is what we think we are looking at. In the long run we are going to have to study more, get more knowledge on endometriosis, look deeper so that we can understand this very complex and enigmatic disease. Thank you.