Endometriosis Foundation of America
Medical Conference – 2012
Early Diagnosis and Complete Excision: Can Endometriosis be Eradicated?
Patrick Yeung, MD
Thank you Tamer and Padma, and the organizers of the EFA, for inviting me to speak today. It is a true honor and a privilege. My disclosures are that I work, or consult for, Lumenis and Covidien.
Today I want to try to address the question of is eradication of disease possible? Again, just to be clear, we are talking about the actual disease. I am going to talk about when to operate and how to operate to hopefully achieve this goal. Just as a quick reminder for us of course, this is a big problem. I always say to patients “Endometriosis is an under diagnosed and under treated problem. It is estimated to be in one in ten women, or 12 million women in the US”. I love to show this slide and mention this study, the Hadfield study. There is a sort of corresponding or sister study that was done in Europe that showed a similar result that the average time from the onset of symptoms characteristic of endometriosis to the surgical diagnosis is 12 years. So that is evidence that truly this is under diagnosed and under treated.
The typical symptoms are things like chronic pelvic pain, which is pain outside the period for more than three months, pain with the period, dysmenorrhea, pain with intercourse and painful bowel movements. I have seen several patients who have had nothing but this symptom - painful bowel movements, usually with the period and even low back pain with the period. But I also like to talk about in looking at and collecting this data what I would call red flag symptoms. We are trying to see if this is predictive or not. These are our questions that I now routinely ask, and if the answer is yes to these questions I think they have to be evaluated. When the question is asked in this way and the patients have this symptom they will light up and say yes. I ask it in this way, “Are you doubling over in pain, or lying on the floor in pain during your period?” The second is, “Do you miss school or work due to pelvic pain?” That is affecting quality of life now and activities of daily living. That to me is not normal. “Have you been to the Emergency room for pain, but not given a specific diagnosis?” Many patients who end up being diagnosed with endometriosis have had this experience. They have been many times to the ER, sent home with pain medications, sometimes they are repeat visitors and they know them and they no longer do any kind of imaging at all and they are just sent home. They are never given any kind of diagnosis. I think that is a red flag. “Are you taking narcotics for pelvic pain? Or pain during the period?” If you have to take narcotics because your periods are so bad to me that is not normal. Some ibuprofen the first couple of days of the period – that is one thing. But taking narcotics just to deal with your pain during the period I think that is not normal, and “Have you taken hormonal suppression or birth control pills specifically for pain but without adequate relief?” So you have pain. You are taking hormonal suppression birth control pills for that pain and it does not relieve the pain, I think that is also significant based upon a quick look I think that is about 80 percent predictive for endometriosis.
So we know this, this is very interesting but our current classification system and staging on the amount of disease does not correlate well with symptoms. We need to know more about the disease. There is something else about the disease, not just extent of disease that might be more predictive.
How is endometriosis diagnosed? This is the problem. Well there has been a trend since the Ling study back in 1999 that was published in the Green Journal, which basically they had 100 women, and if they had pain suspected to be from endometriosis they were given Lupron, and the Lupron treated group felt better basically. This is now used as empiric treatment for pain. In fact in my residency I was taught that endometriosis is pain. I remember that clearly that phrase being used. In fact if they felt better with Lupron or hormonal suppression they had endo. What people do not realize is in this study when they went on to actually look at the rates of endometriosis in the patients that felt better versus placebo; the rates of endometriosis were not statistically significantly different.
There is a follow up study or another study since then. This is now a retrospective study, with C.Y. Liu and his fellow at the time. They basically looked at, this is now retrospective, looked at responders and non-responders to Lupron. Did they feel better with Lupron or not? They went back to look at the rate of histologically proven endometriosis and again, the numbers were not different in absolute numbers, but again, also not different statistically. Response to Lupron, and I would say hormonal suppression, is not predictive of endometriosis. ACOG in its recent practice bulletin agrees with that statement.
This is an interesting study. Chapron from France in 2011 looked at markers for potentially identifying deep infiltrating endometriosis, or more significant disease at least by extent of disease. His results; he looked at patients who ended up having DIE or deep infiltrating endometriosis and they had this history, they had a history of severe dysmenorrhea and hormonal suppression treatment for that severe dysmenorrhea. They found that patients with DIE had more frequent birth control pill use, longer duration of pill use and earlier use, meaning before the age of 18. Also when looking at their adolescent history patients with more significant disease or DIE had more absenteeism from school during their periods. Conclusion? They concluded that birth control pill use history and adolescent history can be markers for more advanced disease. This also implies that the birth control pills as hormonal suppression are not necessarily doing what we want them to do. We want them to feel better with the birth control pill or with suppressive therapy but we are also trying to suppress progression. This data indicates that that may not be happening as well as we think.
Here is another study published by the Chapron group also in 2011. This time in the Journal of Pediatric Adolescent Gynecology and they concluded that “the possibility of diagnosing endometriosis earlier when suggested by clinical history could lead to less extensive surgery and thus to less damage”. So we know that endometriosis can progress, admittedly it does not always progress, but as a surgeon, or surgically, if we can get it earlier in the process that should make it easier to see and to treat more completely. Our study would support this statement. Of course, this has to be verified.
ACOG, as I mentioned, does state, “That response to empiric therapy does not confirm the diagnosis of endometriosis”. There are two recent practice bulletins on endometriosis. Again, ACOG says that the diagnosis of endometriosis can only be made during surgery. You have to at least see it, even better, cut it out and send it off to pathology for histologic diagnosis. Surgery is the Gold standard to diagnose it and potentially to treat it. And we can do what is called see and treat laparoscopy.
Now you have decided to take the patient to the OR to have enough symptoms to justify and be suspicious for endometriosis. Well, what does it look like? Half the battle is you have to see it. The other half of the battle is you have to treat it. So, I borrow from Dan Martin’s atlas, this is the classic black or brown powder burn lesion but it comes in many other forms. I love this slide here because you have several different forms of the disease in the same slide. So you have that dark or brown/black powder burn lesion, but also a red lesion and white lesion, or scar lesion, and clear or yellow vesicular lesions all in the same slide. You have to know all the different forms of it to be able to then treat it. In younger women it is often more atypical or subtle and earlier in the natural history. You have to be able to identify the atypical or subtle forms like the red and white lesions.
I borrowed a term from Redwine “near contact laparoscopy”. You have to look very carefully. If you were to stay back here, it looks good. It is not until you zoom in with your camera – and I loved Steve’s talk yesterday about how you can really see better with technology – you zoom in and you see there is a retraction pocket. We are going to zoom in even closer now to look at the bottom of that retraction pocket and now you start to see some brown/black lesions. Some red and white lesions over here, there is another lesion inside that fold. You have to lean on that fold to see the inside of it. But that is disease at the bottom of that pocket probably causing the retraction pocket and pulling the peritoneum in. That pocket has to be treated. I think that cannot be adequately treated there are some other lesions in here once you pull that you can see, there is a white lesion there, that cannot be adequately treated by ablation. That has to be excised. Here is another example. So now we look at the right uterosacral ligament and just inside that. If you stay back here with your view and you have to get all that fluid out, it looks okay. But now we are going to zoom in and again, do what is called near contact laparoscopy. Lean this right uterosacral ligament back, now you start to see that there is a white lesion here, a couple of brown spots here. You would not have seen that before until you zoomed in and looked around all the nooks and crannies. There are some spots here, these actually ended up not being endometriosis. The other spots I showed you were endometriosis proven by histology. Here in the left ovarian fossa, not until you zoom in do you see these white lesions, brown lesions. There are also some other lesions inside the left uterosacral ligament here and the uterosacral ligament itself, there are some spots here. These are very subtle. This is in a younger patient. You have to look closely, systematically with near contact laparoscopy to find it all.
Then we are going to treat it. So let’s say we have seen it all and as we go forward with technology we are going to have better chance to see the endometriosis. How do you treat it? Well, in this debate of excision versus ablation we did a review in 2009 looking at the best evidence at the time in the surgical treatment of endometriosis. At that time there was only one randomized controlled trial. This did not show a difference but it was underpowered. Whenever there was a non-significant difference we looked at the power of the study, this was only 24 patients, so clearly underpowered. Since then there has been another study, another randomized controlled trial by Healey et al. This was adequately powered before the study was done. This study also did not show a significant difference between excision versus ablation but there were non-significant trends and other types of pain, in particular dyspareunia or pain with intercourse and dyskesia, pain with passing bowel movements. It also said something very interesting. It said that these results may really only be achievable by a general gynecologist and not necessarily applicable to a specialist. They recognized that there were other non-comparative trials published that showed better results than what they had published.
Surgically, I am going to offer to you some scenarios where I believe excision makes more sense and can lead to more complete treatment. One, and I think this is shown in the literature, deep or infiltrating endometriosis, if it is invading you have to get to the bottom of it. If you just try to ablate it you might just char the tip of the iceberg and not get down to the bottom of the lesion. In fact that char will prevent the energy from going deeper. I think people will agree on that for the most part. Over a vital organ, if you are near the bowel, the bladder or the ureter, most people would not, nor should they, ablate in those areas. They cannot tell how deep the energy is going or how the energy is spreading. Lesions can be safely excised off those areas. If there is a whole patch of it, if you try to ablate a whole patch of endometriosis you would potentially create a lot of char. If you can cut out the patch cleanly, then I think you have less of a chance of creating char and potentially adhesions. You can treat the area more completely and effectively. Retraction pockets: as I showed you I think that is another scenario where ablation, to try to get down to the bottom of the retraction pocket can be difficult if not impossible. I think those have to be excised. And lastly, endometriosis over the fallopian tubes; in my hands I would not try to use electro-cautery to treat endometriosis over the fallopian tube. That would pucker the tissue. My cutting tool of choice I will show you is the CO2 laser and I have used that in particular to excise lesions even over the fallopian tube.
In this debate of excision versus ablation if the lesion is truly superficial and there is just a little pinpoint spot maybe ablation is adequate. But I will ask you the question, can you always identify when it invades? I make this point all the time that we all have been fooled and you cannot really tell which ones invade. I think that is the real problem with trying to only use ablation to treat the disease.
How would you treat this? Let’s have a couple of clinical scenarios. Here is a lesion, the color is a little bit off but it is sort of a black/brown lesion with some white scar tissue around it over the left ureter. Well, here is a similar lesion, again, I think completely treating the disease by excision is the most important. My cutting tool of choice is the CO2 laser. I like it because it is a non-contact tool. You do not have to use it. I use it in the way that I was taught which is to circumscribe the lesion in situ, and you can see even though I am right over the left ureter here, as long as you keep that laser moving it will incise without contact one layer at a time. It is very precise. Once you raise an edge then you can start to retract the specimen away from the vital organ below. The vital organ is no longer the backstop and you can safely excise that lesion now away from the vital organ below, in this case the ureter. The same would be true over a lesion for example with the bowel. Again, this is not necessarily a typical lesion. This is a white scar lesion. This is a rectal probe, an EEA sizer in the rectum showing that this is actually an anterior rectum lesion. Same thing, I would circumscribe it in situ. I would circumscribe it until an edge is raised and you can see, you can really be quite precise about it and incise one millimetre or one layer at a time with a non-contact CO2 laser. Once you have raised the edge then you can start to peel the tissue away from the vital organ below. In this case the bowel. I look for what is called the tether here, which is the line between the normal tissue and abnormal tissue to know where to incise. When you can, you can use the backstop for the CO2 laser. This is a free beam CO2 laser. We have a target which is helpful to know where the end of the beam is and there you can see we have a nice, clean excision patch, very little char, so I would say very little chance for adhesion formation and we excised off a vital organ.
How would you treat this? Well, this was that same retraction pocket that I showed you before. Often times there can be much deeper retraction pockets close to the bowel, what have you. I think that these have to be excised to treat them completely and safely, which we did with a nice clean excision lines. That will just heal over like a skin. It will re-peritonealize. Here is the example of some lesions or spots on the fallopian tube. Again, I would recommend that that not be treated by ablation. I think that would pucker the tissue. But that can be cleanly excised off the fallopian tube. In this case I used the CO2 laser to do so.
There is a video I made that can be seen online, I will not go over it now at this webpage. Basically it goes over a little more in-depth about my technique for CO2 laser excision. I made this video to demonstrate how the CO2 laser can be used, not necessarily the way it was traditionally used, which is just to ablate, some might say vaporize, but as a clean, cutting tool.
What is the recurrence rate? In some studies here it is about 40 to 60 percent in one to two years after ablation. Those are published studies. Others have said it in the way of 10 to 20 percent per year recurrence rate after ablation. That is pretty high. Even in a more recent study by Doyle this is true even if postoperative hormonal suppression is used, which is probably the common recommendation, especially in teenagers if you find endometriosis and prove endometriosis by histology. Even with hormonal suppression postoperatively the rates of occurrence after ablation are about the same. We published the first prospective study looking at complete excision in teenagers. This was 20 teenagers, which is a relatively large population for teenagers. They all had, well not all of them, the majority had previous hormonal treatment or surgical treatment and the majority had awful or poor quality of life. They underwent complete excision. These are their pain scores, you can see that there was a significant improvement. There was also a significant improvement in quality of life scores.
We had a chance, I put it this way, we had a chance to look back at about 50 percent of patients, actually 45 percent of patients. They had enough pain to want to go back to look for the actual disease, to look for endometriosis. Again, to be clear when asked their pain scores and their quality of life if they were feeling better but this gives us a chance to go back to look for actual disease. Because we felt like complete excision was achieved we did not specifically recommend post operative suppression for disease or disease suppression. They could take it if they wanted to, one third took it which means two thirds, or the majority, did not take postoperative suppression. But in zero patients did we actually find recurrent or persistent disease. So the goal of complete treatment is complete treatment of disease in all of its forms, both typical and atypical.
I want to address…we need to know more about endometriosis, clearly. But people say, “Well, shouldn’t the endometriosis keep reseeding?” as one of the reasons why it would always come back. This study here by Koninckx was very interesting. They looked serial laparoscopies and they documented the locations of the endometriosis and they found that the locations remained constant. But the depth or volume in those locations changed or progressed over time. It is not necessarily that the endometriosis keeps spreading or reseeding, that may be why if you can completely treat the disease it does not necessarily come back.
We had a group write in right after our publication to say “Your results of no recurrent or persistent disease on second look laparoscopy in teenagers, a population we know always comes back, are impossible because of this entity that we know of that exists called invisible endometriosis”. We had to address this issue. With permission we published this graph in our response to the letter to the editor, by Redwine, to make the point first off that the idea of invisible endometriosis came out of a study done 25 years ago in open surgery. So, surgeons are looking for endometriosis of the peritoneum with the naked eye. They basically biopsied what looked like normal peritoneum and it came back on histology as endometriosis. So they said, “Well invisible endo exists. Endo you can’t see and so we are not going to be able to get it all”. That is why people say you have to put the patients on postoperative suppression. Well now, again, as Steve made the great point yesterday, we have a much better ability than before to see with high-def optics with laparoscopy. There have been several studies since that Murphy study 25 years ago looking at this issue of invisible endometriosis now done by laparoscopy. The benefits of laparoscopy as I showed you are what - illumination and magnification. You can light things up, you can look around the corners, you can zoom right into the tissue to be able to see better. This shows very elegantly that basically the closer you get to the tissue the rate of invisible endo goes down to basically zero. In this last study in fact it was zero. So we can see much better now and we are nearing the potential, I would say, at least of being able to “see it all and thereby get it all”.
I just wanted to show this because people always ask, “Well, what does it look like after you excise the large patches of peritoneum”. Well, this is a second look on a young patient that we excised several areas of peritoneum and it can heal over quite well. I think what is important is that it is clean and dry and there is little char and it can reperitonealize without many adhesions.
We conclude from our study that early diagnosis and complete excision is clearly part of a management plan for pain. I tell the patients, “You know, I cannot promise you’ll never have pain again but we can expect that you should feel better”. But the implication or the potential of this data is that it is potentially more important for fertility. If you look back and there is no actual disease then the disease cannot progress. That may be more important for fertility, for either restoring and/or preserving fertility. Again, we have some studies that show that suppressive therapy does not necessarily suppress the disease. I think that is very exciting and has to be systematically studied. We are going to continue to follow these patients going forward.
There are some who would say that endometriosis basically should only be treated by experts. An expert I would define is somebody who can look carefully and closely, recognize the endometriosis in all of its forms and excise it or treat it adequately or completely wherever it is found.
That is the message I want to leave to you. We do advocate early diagnosis, which is a very similar message to what Padma and the EFA advocate and I want to quote a well-known physician who treats endometriosis, Dr. Tamer Seckin, who has said, which I really respect, “Early diagnosis and complete excision is the best prevention” of the disease. I think that is a very consistent message in this conference here.
If I have a couple of minutes I might just give a very quick, short anecdote. I developed this interest in treating endometriosis before I got married. When I got married my wife had never even heard of the word endometriosis. After about a year of trying to get pregnant she said to me, “Maybe I have endometriosis”. I said, “No way”. She had had painful periods her whole life and thought it was normal, more importantly was told it was normal and believed it. She ended up having bad stage four endometriosis, in fact, inflammatory, raw endometriosis. She had excision to remove it and then further surgeries for the adhesions. After several years of infertility we adopted. So we adopted little Lucy here and then she got pregnant. But she would very much echo the message that Padma has, which is if she could have been diagnosed a decade earlier she could have avoided a lot of pain and had her fertility probably better preserved. I think that message is very important. If we can get the disease earlier I think we have a better chance of treating it and helping our patients, and we can do better for our patients.
Thank you very much.
