EndoZONE Presents from the World Congress on Endometriosis, May 2000, London, England

Professor Hugo Verhoeven interviews Professor Jacques Donnez

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Dr. Hugo Verhoeven:  "My name is Hugo Verhoeven from the Center for Reproductive Medicine in Dusseldorf, Germany.  I am a member of the Editorial Board of OBGYN.net, and I’m presently reporting from the Endometriosis World Congress in London.  I have the pleasure to talk to Professor Jacques Donnez from the Universite Catholique De Louvain, Belgium who is one of the leading people in the field of endometriosis.  Jacques, thank you very much for giving me this pleasure.  A few years ago everybody talked about "endometriosis is endometriosis," meaning whether the endometriosis was situated on the peritoneum, in the ovary, or in the recto vaginal space - it’s the same disease and the treatment was the same.  It was your idea to say - that’s not true, we have here three different entities, with different origins and therefore a different therapy is necessary.  Tell us something about your ideas on this topic."

Professor Jacques Donnez:  "In fact, the story of endometriosis is a big story because until twenty years ago, as you mentioned, when we did a laparoscopy we were able to see typical black lesions, and it was called typical because everybody was convinced that endometriosis was black lesions.  Then by improving our ability to detect subtle lesions, red lesions, popular, clear, visible lesions by taking a biopsy and proving that these red lesions are very active lesions, we were able to classify different types of lesions.  It’s very important because it’s a difference in the activity of the disease, and it’s also very important because what we considered for years and years as endometriosis was probably one of the less active forms of the disease.  So more and more attention was paid to analyse and to observe the activity of red lesions, which for us is the first stage.  It’s a view that if we speak about peritoneal endometriosis, that peritoneal endometriosis is the consequence of their implantation of menstrual labouring after reflux through the fallopian tube.  That was also one of the hypotheses that clear lesions and red lesions were the first step, that was like fresh endometrial on the surface on the peritoneal and then because a thinner main of vascularization coming from the rectoperitoneal tissue there was a possibility of growths; then by ablating and by fibrosis, black lesions appear and probably in some instances, it could go through the white lesions which are completely inactive lesions.  That is the facts on peritoneal lesions.  You also mentioned in your question that we clearly identify three different entities, and I think it’s very important.  First, think about the symptoms, for example, it seems so obvious; a patient with infertility is ovarian and peritoneal endometriosis.  A patient with pelvic pain - dysmenorrhea, severe dysmenorrhea, deep dyspareunia are very often recto vaginal septum nodules.  So on principle, if you go from the symptoms to the diagnosis, there are already different entities.  If you look inside by laparoscopy there are also three different entities, for example, the ovary, the chocolate cyst - 90% of the lesions are just the fluid, peritoneal lesions - 90% is stroma fibrosis, and the recto vaginal nodule - 90% is hyperplasia of the smooth muscle so then it’s obvious.  I cannot imagine that we forget this principle of obvious histopathology to classify the disease."

Dr. Hugo Verhoeven:   "Jacques, let’s go back to your statement that peritoneal endometriosis is caused by retrograde menstruation.  What is the origin of the endometrioma, the endometriotic cyst of the ovary?  Is that also retrograde menstruation causing implantation of endometriotic tissue on the ovary and additionally covered with an endothelium? Then I would like to switch to the aetiology of  recto vaginal endometriosis."

Professor Jacques Donnez:  "Ovarian endometrioma for us is the consequence of metaplasia from the invasion of the mesothelium.  First, we have an argument for that, it exists in Rokitansky syndrome, where there is no reflux of endometrium."

Dr. Hugo Verhoeven:  "What is a Rokitansky syndrome?"

Professor Jacques Donnez:  "It’s the absence of the uterus and vagina so that there is no endometrium, no menstrual bleeding, no fallopian tube, and there is no reflux.  Even in this condition, in some patients with this syndrome, endometriotic cysts have been described. Similarly, until we have metaplasia has been proof of the serous mucin, serous cyst, mucinous cyst, a lot of cysts in the ovary, why not for the chocolate cyst?  We have proof by serial section of the whole ovary that, in fact, we can detect the metaplasia from the mesenterium invaginated in mesenterium in glandular tissue so that we are convinced that endometrioma is an intra-ovarian pathology due to the metaplasia of inclusion from the mesenterium surface."

Dr. Hugo Verhoeven:  "Could you possibly explain the word metaplasia; what does that mean exactly?"

Professor Jacques Donnez:  "Metaplasia means that the tissue, for example, here in the mesenterium which is just like ancilliary tissue, cannot undergo the process of metaplasia so that it means that it can go to the process of differentiation.  It can give another tissue, that’s the metaplasia from mesenterial to endometrial gland that is a differentiation from a non differentiated tissue but able to go to another tissue - that’s the metaplasia theory.  It’s a just the change from a tissue to another tissue."

Dr. Hugo Verhoeven: "Is there a way back; can the metaplastic tissue transform again to original tissue?"

Professor Jacques Donnez:  "In fact, when you have this type of lesions such that this is the final step of the metaplasia process, we cannot go back to the mesenterium again.  Mesenterial which covers the ovary is like the serametic-paterium and the serametic-paterium can be transformed in all types of tissue and especially in all ovarian tissue and during the fertile life so that in fact is a real potential of transformation but when the transformation is done, there is no possibility to regress."

Dr. Hugo Verhoeven:   "The third entity - recto vaginal endometriosis, it’s one of the most important reasons for pain.  How does recto vaginal endometriosis originate?"

Professor Jacques Donnez:  "The basis is first the observation, we have the largest series in Belgium and probably the toxins which are the environment in Belgium provoke a dramatic increase of this pathology.  We cannot explain, twenty years ago when we were assistants, we didn’t have this type of pathology.  Everybody tells us - you now have the magnetic resonance, you have the vaginalography, with this you are able to detect more - it is not true.  The nodule of the recto vaginal septum is diagnosed by pelvic examination exactly like we did twenty years ago so there is a dramatic increase of that.  We have the largest series, and we have observed after two or three years of therapy of this disease that sometimes there was only nodule lesions in the recto vaginal septum and that some patients have no peritoneal or ovarian endometriosis, meaning that it could be another analogy.  Then we started a prospective study where we started to analyse all the nodules resected by laparoscopy by serial section.  We’ve analysed normal tissue from the rectoperitoneal space, and we first were able to detect in all women Mullerian remnant in the recto vaginal septum. Similarly by serial section, we have clearly proved that Mullerian remnants were undergoing the process of change in endometriotic tissue.  That is the histological proof of the continuum between the Mullerian remnant present in the recto vaginal septum and so called endometriotic glands and also by discussion with Professor Brosens six or seven years ago, we were surprised to see the histology of the lesions.  We were enable to recognize the typical endometriotic lesions with gland and stroma, we had in front of us hyperplasia of the psoas muscle, so that was the beginning of the reflection of the thinking about the process that we have called greater adenomyotic nodule of the recto vaginal septum.  Most of the disease is the rectoperitoneal and what is important to say for this disease is it’s often under diagnosed because by laparoscopy you just see the top of the axilla."

Dr. Hugo Verhoeven:  "That’s the second important thing, let’s now go to diagnosis.  You said earlier: infertility most of the time is caused by peritoneal endometriosis; pain is caused by ovarian or recto vaginal endometriosis..  So what are the tools for the diagnosis of those three different types of endometriosis?  Later on we will come to the therapy."

Professor Jacques Donnez:  "If a patient is consulting for infertility, even if our exams are normal, I think that we have to do an exploration of the peritoneal cavity.  I think if we don’t suspect any endometriosis but if we want to be sure that the pelvis is clean, I think that’s really an indication for the metal curette but also the block collaboration with Professor Brosens and the < which is the THL, the consult on laparoscopy because you are sure and you can say to the patient - your pelvis is clean or if there are some endometriotic lesions.  Now in my department, if we suspect endometriosis because on pelvic examination the patient has some small nodules on the uterosacral ligaments, the probability of having endometriosis is nearly 90% then we will propose imaging immediately a laparoscopy with the dye test and at that time we will destroy the endometriotic lesions.  Now, as I mentioned when I start in the case of infertile women with apparently no lesions, in many cases by pelvic examination, by vaginal ultrasound, or by dosage of the CA125, which is a marker of endometriosis, we will be able to detect endometrioma.  We will not be able to detect peritoneal lesions but cystic lesions of the ovary and we will be able to detect this type of lesions, and then we will do major laparoscopy.  In the case of an ovarian cyst less than 3 cm, what we propose is the destruction of the internal wall of the cyst by laser.  If the cyst is larger than 3 cm, this issue of treatment must really be discussed.  Why, because you like me have been confronted by women who’ve undergone surgery in other departments with extensive ovarian surgery and will come afterwards to your department or it might be my department for IVF and we have many difficulties to stimulate numerous follicle.  What does it mean, it means that surgery on the ovary for endometriosis must not be very aggressive, it must be conservative and a laparoscopy doesn’t automatically mean conservative.  We are to be laparoscopists and conservative so that in case of larger cysts what I prefer to do is to drain the cyst, this aspirated chocolate cyst, then prescribe for three months a GnRH agonist and go back for a second look laparoscopy.  Why, because then the capsule of the cyst is atrophied.  What is pathological for ovarian endometrioma is not a capsule, a capsule is just fibrosis, there is no endometriotic elements.  All the endometrial elements are some epithelial cells and stroma cells on the surface of the cyst and we just have to burn to coagulate the internal wall of the cyst and by shrinkage it will actually be a good reason."

Dr. Hugo Verhoeven:  "After treatment with a GnRH agonist, what is the percentage of patients that will produce another endometrioma ? In how many cases will the cyst fill up with endometriotic  fluid again?"

Professor Jacques Donnez:  "You have to keep in mind that that drainage followed by GnRH agonist and at the end of GnRH agonist, I will repeat the laparoscopy."

Dr. Hugo Verhoeven:  "What do you do at that moment?"

Professor Jacques Donnez:  "The vaporization of…"

Dr. Hugo Verhoeven:  "You vaporize, so you do not excise anymore."

Professor Jacques Donnez:  "Exactly."

Dr. Hugo Verhoeven:  "We learned that you do not excise cysts anymore.  You do drainage and a coagulation or a vaporization of the wall."

Professor Jacques Donnez:  "Exactly, and I don’t do any cystectomies anymore because there is always a risk to remove together a lot of photocytes which are just the leads of the capsule."

Dr. Hugo Verhoeven:   "The final part – the treatment of the recto vaginal endometriosis, you’re an expert on this topic, tell us about it."

Professor Jacques Donnez:  "That’s very simple there is no medical therapy, neither Progestagens nor GnRH agonists because like adenomyosis of the uterus, it’s hyperplasia of the muscle.  You can have a possible reduction by GnRH agonist of 10%-20% of the size.  Decreased inflammation is stopped, then the patient can be improved but we have to consider that medical therapy is not efficacious in the treatment of nodules.  The only possibility is the excision of the nodule, which can be performed by laparoscopy.  Again, I would like to stress that this type of nodule gives us an impression that the rectal wall from the anterial part is involved in the process of endometriosis.  I’m not sure of that, and I’m convinced that especially in the United States some laparoscopists are doing too aggressive surgery; removing a part of the rectum, a part of the bowel, and increasing the morbidity of these types of surgery.  On the contrary, in my department if the rectal mucosa is normal, I never do rectal resection."

Dr. Hugo Verhoeven:  "But you perform a resection of the posterior wall of the vagina."

Professor Jacques Donnez:  "But I do the posterior wall resection, that is the most important thing because if you do pathology, it’s the pathology of this part that you will see the fibrosis and glands, just the disease, and sometimes there is a metaplasia of the vaginal mucosa into endometriotic tissue and adenomyosis, thick tissue so that you can see with a speculum examination some bluish spot in the vaginal fornix.  I think that the most important thing to cure the patient - to decrease the symptoms of the patient - is not to remove the rectal wall, it’s to remove all of the vaginal posterior fornix, that’s what we do systematically."

Dr. Hugo Verhoeven:  "Jacques, my final question is always the same - what about the future, tell me about your dreams?

Professor Jacques Donnez:  "I think that for peritoneal endometriosis, it’s a view that we will go to medical therapy, at least to prevent the recurrence or to prevent the regrowth of the disease, and what we have heard this morning about the matrix metalloproteinase of the angiogenesis process are probably two ways of the future.  But we have also understood this morning that the way will be very, very long between the understanding of all these growth factors and cytokine and their application in the clinical study but it’s a way of treatment.  Concerning the recto vaginal endometriosis, I’m very surprised in the dramatic increase of the prevalence this last year, and I think that must be treated in the future by prevention and by knowing more about that."

Dr. Hugo Verhoeven:  "But you have no idea what exactly the reasons for that are?"

Professor Jacques Donnez:  "Yes, I have some idea but when I mention that in front of the TV news, I was confronted with so many people but I’m really convinced that dioxin of other environmental toxin have something to do with the growth of this particular disease.  As you know, we have known since 1993 that the milk of women in Belgium is the most concentrated in the world in dioxin, we know that from an official report from the WHO but not anymore.  When we speak about that to the Minister of Health in Belgium, he can’t believe it.  He says - please prove to me that what you are telling me is true, the three things another ten years but I know that somebody has statistic and is working very hard also on biological pathways between a product like dioxin and the angiogenesis process.

Dr. Hugo Verhoeven:  "Jacques, thank you very much."