Endometriosis Foundation of America
Endometriosis 2013 / American Retrospective: The Challenge of Deep Fibrotic & Infiltrative endometriosis
Ted Lee, MD
I want to thank Tamer, C.Y. and Harry for inviting me and including me in this event. I am deeply honored and humbled by this invitation. A lot of speakers here today, as well as the speakers in the previous conference in the previous years I hold tremendous respect for these people. These are the people I idolized as I was coming up in the ranks.
I was asked to talk about the challenges of deep infiltrating endometriosis, American perspective. I worked very hard to keep it American but in the end I could not really make it American, it is really a global perspective because many of the publications in the literature come from all over the world.
Let us start with a little video clip. This is a patient with deep infiltrating endometriosis involving the parametrium. It is very, very close to the ureter and it is very, very close to the descending branch of the uterine artery. This is a patient with pelvic pain and also has infertility and you try your hardest to remove as much endometriosis as possible, meanwhile trying to minimize injuring the uterine vessels and injuring the ureter and so on. Basically, you do a lot of this job in blunt dissection, feeling for the weaknesses and so on. In this case I am using monopolar energy, which I learned most of my monopolar energy techniques from Dr. C.Y. Liu. I can see the descending branch of uterine vessels is intimately involved with the endometriotic process in trying to create this nice tissue plane. A little bit probing a little bit blunt dissection...by section just to...the blunt dissection let me note where the tissue plane is and try to see where I can attack it. I am trying to completely remove the implant from the surrounding structures.
You can see the ureter is over there. As we hopefully do a decent job of removing these deep endometriotic implants in the parametrium, and while preserving all the patient's uterine vessels, the ureter we hope that we excise this endometriosis as completely as possible. In the end after you finish the dissection then you go back and look. The ureter is right here is a medium umbilical ligament. The...nerves in the corner right here. Everything was left intact and you feel that you did a pretty decent job. You give yourself a pat on the shoulder and say "decent job". But is that good enough? Even if you try hard and you are trying to remove the endometriosis as much as you can what are we doing?
Koninckx's group have published in this article back in 1990 and in this article they noted that the probability of leaving the margin - if your endometriotic implants is deeper than 8 mm. At lot of times we only have deep infiltrating endometriosis while working very, very close to a lot of implement structures, the bowel, bladder and ureter and so on. A lot of times we figure we have removed everything but in reality if you look at the study we actually leave some disease behind.
But the question is what is the implication of leaving some disease behind? Does that result in higher recurrence rates? Does that result in high recurrent pain? We do not really know that. This is the only double blind randomized trial comparing excision endometriosis versus placebo. As you can see the group was divided to the delayed surgery group where they received a diagnostic laparoscopy first, followed by real excision six months later. The second group had the immediate surgery from the outset they had excision endometriosis and this is followed by diagnostic laparoscopy six months later. You can see there is a tremendous placebo effect. Of all surgical treatments for endometriosis the placebo effect is very, very high and that will last about six months.
In this group here the second time when they had the real surgery their pain improved tremendously from 32 to 83 percent. So we know excision endometriosis does work in these patients. The patients who got immediate surgery, meaning that they got excisions endometriosis first, so about 80 percent of them feel that they have relief from their pain but six months later or a year later that percentage was 53 percent. That is in a short period of one year, it went from 80 to 53 percent. So this is very disappointing. I was kind of shocked to see that.
Let us look at some of the larger retrospective studies that have been published. Dr. Redwine had a pretty big study, 359 patients with a two to nine year follow up. Most of the patients had stage one disease in his patient group. He reported a 19.45 percentage five year recurrence rate. That was defined by histology or by visual inspection. Actually, more of the patients got operated on about 36 percent of the patients had reoperations in this case series. Nineteen point four percent, and usually that is what we call in the patients, your recurrence rate is about 20 percent.
This is another study by Ray Garry's group in England. The difference in the study is that the patients have a higher stage of disease. Over 54 percent of the patients had stage three disease or above. Many of them had previous surgeries. The show that all parameters of pelvic pain, dysmenorrhea, menstrual pelvic pain, dyspareunia and dyschezia, all the pre and after surgery although scores get better. Again, this case series reports a reoperation rate of 33 percent about two thirds of those patients have confirmed endometriosis. If you do the math then they give a recurrence rate of 22.4 percent, which is not a whole lot different from Dr. Redwine's study which was 19.5 percent. It is slightly higher, perhaps because of the higher stage disease in this population.
The reality is the true recurrence rate of endometriosis is not known. Because we have many patients who have pain but have chosen not to have another surgery. And there are maybe patients who have endometriosis who are asymptomatic. So likely the true recurrence rate is going to be higher than what we see in the previous slides.
This is the longest follow up study on excision endometriosis versus excision plus hysterectomy. You can see here a seven year follow up where over 50 percent of the patients had another surgery. If you look at the subgroup of younger patients between 19 to 29 years old over 70 percent of these patients had another surgery. That is pretty alarming. When you compare to the hysterectomy patients, if you do hysterectomy plus excision endometriosis only 8.3 percent of the patients have a reoperation. That is pretty astonishing.
In other words, if you have conservative excision endometriosis and compare that to hysterectomy plus excision endometriosis you are three times more likely to have another surgery. And, if you compared that to excision endometriosis plus hysterectomy plus BSO your risk is six times. Why is it hysterectomy offers higher success rates?
Well, you can have concurrent uterine pathology like adenomyosis, you could have degenerating fibroids the cause of the patient's pain or it could be incidental endometriosis. Pioneers like Dan Martin teach us how to recognize endometriosis but when we recognize it does that mean endometriosis is the source of the patient's pain? A lot of times endometriosis is incidental and has nothing to do with the patient's pain and the pain may be uterine in origin. The other thing is you eliminate retrograde menstruations. What it does is it decreases the disease paradigm and that might allow the body's immune system to clear the disease as well. And obviously with BSO you eliminate hormonal stimulation. Those are the four reasons why I think hysterectomy offers higher success rates compared to conservative excision. To a lot of people in here it fails to surprise, pretty depressing data.
How about the ovaries? While one of the roles of the ovaries when you are doing hysterectomy for endometriosis, what do you do with them? In this study from Hopkins they say that if you keep your ovary at the time of hysterectomy for endometriosis you are six times more likely to have recurrent pain. Then for reoperation you are eight times more likely to have reoperation if you keep your ovaries. The problem with this study is that in this study most of the patients were done by various surgeons from IEI, from oncology to general gyn, even renal indication for surgery whether it is for pelvic pain or adnexal mass. Most of the time it is done without hysterectomy so my gut feeling is that a lot of this hysterectomy endometriosis was not excised at the time of the hysterectomy.
What happens when you do not excise the endometriosis at the time of the hysterectomy? As you can see in here, the lighting is not very good, you can see the endometriosis here. Here is the vagina, here is the rectum, here is another endometriosis over rectal serosa, and this is a pile of lesions over the...sacral. You can see a little bit better here. So when you do hysterectomy and you leave endometriosis behind a lot of times the disease may not regress. Maybe this will take some time and the body may be able to clear it by itself. But in this case this patient clearly had persistent endometriosis after hysterectomy.
This is another, more dramatic case. This patient had abdominal hysterectomy and she continued to have monthly periods after her abdominal hysterectomy. She had a large golf ball sized nodule situated between the bladder, the ureter and the rectum. She was cauterized multiple times and was treated for...tissues. You can see the size of the nodule. Once I put it in my hands you will appreciate the size of the nodule even better. Clearly, in this patient hysterectomy did not cure this patient's disease.
If you look at the Hopkins study where hysterectomy was done without excision 62 percent of the patients had always kept having reoperation. On the other hand if you compared to the Cleveland Clinic's study, Falcone's group, only 13.4 percent of the patients had another surgery when they kept their ovaries. In the Cleveland Clinic study, the Falcone study they felt that with good excision endometriosis at the time of hysterectomy your risk of reoperation compared to BSO is only 2.4 percent, and it is not statistically significant versus eight times in the Hopkins' study. That means the effort that you put in to excise endometriosis at a time of hysterectomy may allow the patients to keep their ovaries and allow them to maintain their hormonal function.
The other thing I think about is does the radicality of hysterectomy make a difference in the treatment of deep, infiltrating endometriosis?
This is a patient who has severe endometriosis. She had it retroperitonealized endometrioma, adenomyosis. The rectum is plastered behind the cervix. And in this case that will require essentially a...hysterectomy. You can see the ureter here. You see ...fibrosis with the ovary and endometrioma extending over here. I am feeling for the internal iliac instead of fibrosis here. I am going to cut through that. Here is the internal iliac. ...bisection to get a feel where things are because the tissue plane does not open up immediately when...and I feel a structure here that is the medial umbilical ligaments, so I know the medial umbilical ligaments is here and internal iliac is here so the uterine must be somewhere in here.
So, this patient, the endometrioma has extended far laterally and I have really no choice but to do a modified radical hysterectomy on this patient. You can see the internal iliac here, I am going to open up the parietal space a little bit better, stretch out the tissues parallel to the internal iliac and the uterine vessels right here. I am going to open up the medial paravesical space. I am going to ligate the uterine and think that it is origin because the disease will require me to perform retro dissection like this. The lateral paravesical space I am going to open it up just to define the anatomy a little bit better. Here is the uterine, here is the ureter and I will take the uterine at its origin. At times modified radical hysterectomy may be necessary for patients with deep, infiltrating endometriosis, with stage four endometriosis. But is there any evidence that supports this kind of approach? Some people still do a simple hysterectomy for...endometriosis.
There was actually a study done by Fedele in Italy where they looked at patients with deeply infiltrating endometriosis. A group of them just had a simple TAH/BSO, the other group had modified radical hysterectomy, BSO with excision endometriosis. They gave them hormone replacement therapy for two years. Thirty percent of the patients who had simple hysterectomy had recurrence of pain versus zero percent in patients with modified radical hysterectomy. In this study that showed that modified radical hysterectomy, tailored modified hysterectomy, does help with the outcome of the patients.
How many people here do presacral neurectomy? Do you think this will impact on the reoperation rate of endometriosis? This is a patient which has had a quick medial presacral neurectomy. I am thinking that there have been studies looking at presacral neurectomy compared with excision endometriosis versus excision endometriosis plus presacral neurectomy. In the study done by Zullo they showed that patients who have presacral neurectomy plus excision endometriosis have overall a 30 percent reduction in pain when compared to a patient with a simple excision endometriosis alone. My thinking is that if you - since most of the driver for reoperation is pain, if you reduce the pain does that reduce reoperation? Obviously presacral neurectomy it is done in a very intricate area with a lot of big, large blood vessels and needs to be done by people who are experienced in this anatomy.
Let us take a poll. How many of you think that presacral neurectomy would change the reoperation rate? Anybody think that presacral neurectomy changes the reoperation rate raise your hands, about two or three people. It does not take very long. This is actually a six minute procedure and I shortened it to two minutes. Here is the presacral nerve. I am going to make a window here and we will take the presacral nerve and completely mobilize it, which takes you right there. There is a lot of interesting anatomy in this area you can see that the...vein here, the left ureter coming over the left common iliac artery. The IMA is right here and the middle sacral is right here, and the right...artery.
This is a study I was talking about earlier. In all parameters of pain whether it is dysmenorrhea, dyspareunia, chronic pelvic pain the patient that gets presacral neurectomy plus excision endometriosis has consistently better pain reduction compared to excision endometriosis alone. My thinking was "well this must at least lower reoperation rate and you have less pain", right? That was not the case. In this study, the reoperation rate was extremely low. A two year follow up was 4.8 percent for both groups. They have three patients out of 63 in each group that had been re-operated on. You are wondering, why is this the case? Why is this the case because all the other studies show a very high re-operation rate. This study was ideal patients. The patients had no prior surgery, all the GI, GU, ortho and psychiatric disorders have been excluded. Any of those disorders were excluded from the study. You have drug abuse screened from the study and they actually had respectable severity in the patient population, about 10 percent of the patients had stage four, 25 percent had stage three and 10 percent had deep rectovaginal disease.
This could also mean that when you have ideal patients, like if you have the right patients operated on by the right surgeon, operated at the right time you can have a very, very high success rate. And this is reassuring in that way.
Take home points: Even in the best hands recurrence and re-operation rate is very, very high in excision endometriosis. If fertility is no longer a consideration hysterectomy with or without BSO should be considered. Optimal debulking endometriosis may allow you to preserve the ovary without significant increase or risk of re-operation. In the case of severe endometriosis, modified radical hysterectomy with BSO and excision endometriosis may allow you to have hormone replacement therapy without recurrence of pain. Well selected patients, well selected surgeon and well selected surgery at the right time the first time, equals high success rate and happy patients. Thank you.
Harry Reich, MD: Thank you very much Ted. I have one question and it pertains to the use of presacral neurectomy. In Boston, Robert Kissner did them 100 percent of the time, every endometriosis case and he did very little cul-de-sac work and many of these people did well. But if you look at present day surgery out of Europe the big thing that they are doing in almost all of these endometriosis cases is showing the nerves of the pelvis with the concept that if we see the nerves in the right place and excise the endometriosis we could preserve the nerves. The patient will have better bladder and bowel function after the procedure. I have a question about doing it in this day and age when the object, like I say, for many advanced people is to preserve all the nerves and remove the disease.
Ted Lee, MD: Well, I think in a patient with severe endometriosis frequently those nerves are involved in endometriosis itself and that is partly another reason they have pain. For me it is obviously where the nerve is, if it is intact, it is not involved with the endometriosis then I think it is reasonable to preserve it. But presacral neurectomy I think is more of an insurance issue, in case you did not get everything and that might give you some relief for the endometriosis that you have not completely resected. As you see that as good as anybody can be in excising endometriosis a lot of times you leave disease behind simply because it is sometimes hard to know where the disease ends and begins.
Harry Reich, MD: Has anyone looked at the long term situation with bowel and bladder function after presacral neurectomy?
Ted Lee, MD: They have. The Zullo study shows that about 15 percent of those patients have constipation symptoms but they are self-limited and it gets better on its own. About five percent of the patients have...and that gets better on its own without any intervention.