Hélder Ferreira MD - Nerve-Centric Surgical Planning in Endometriosis: From Neuroinflammation to Excision Strategy

So dear colleagues, dear friends, I'm very grateful to Professor Saskin for the invitation to be here in New York in this amazing meeting that I follow since the very beginning. In fact, Tamara, you know that you have been an inspiration for my career in this field of endometriosis that we all know that affects so many women worldwide. And we need important men, important women that work, make research, perform surgery in order to offer the best care to all these women that have endometriosis. So my topic after this, I also want to say a few words to Eric Rich that was here and also was an inspiration for my career. I'm really happy to join him in this session. My topic is of paramount importance. I'm also thankful for the opportunity to speak about the nerves. And in fact, we are knowing more and more about them because of pathology, as was said, but also because we have better camera systems, laparoscopy robotics, magnify the vision, eye definition that gives us the opportunity to see better and to identify smaller anatomical structures.

So I will focus on this surgical nerve-centric approach in endometriosis. There is a new parade that we are shifting towards making not only pain treatment an endpoint, but also pelvic organ function endpoint. Because what happened at the beginning was that we tried to excise the disease, we tried to treat the pain, but sometimes the location of disease was close to some nerves, close to some functional structures, and we could impair that function. So there is this new paradigm that we have to fix the pain, but also keep the function. This pain resolution addresses the neuroinflammation and the neurogenic pain mechanisms and organ function, it's preserving the urinary function, the deficatory or disaster function, but also the sexual function that is so important in these young ladies of reproductive age. And we know that there is that critical risk zone, the posterior and lateral deep endometriosis where there is the highest risk of damaging some autonomic nerves like the inferior hypogastric nerves and the inferior epogastric plexus.

So there is this framework that is mapping the nerve risk autonomic and somatic before the procedure. So it's important to listen very careful our patients, where is the pain, when happens the pain, what increases the intensity of the pain. Also, the systematic identification of the nerves. When we go for the minimally invasive surgical approach, we can also do this intraoperative functional assessment. And of course, at the end of the procedure, we can work and we are working more and more in this rehabilitation that is a long-term functional follow-up and recovery.

Few words about the cause of the pain, this neuroangiogens that was mentioned before, there are some molecular drivers like the vascular endothelial growth factor and the nerve growth factor that act synergistically that also the pro- inflammatory cytokines. And this epoxic microenvironment of this lesion strikers the expansion and the increase of the tissue. So there are this multiple growth promotion angiogenes and neurogenesis in this reciprocal interaction when we speak about pain in endometriosis. And basically in this, my presentation, the learning objectives are to discuss a bit this molecular mechanism that cause the pain, the risk stratification, but I will focus more on the surgical strategy.

This is the anatomy. Unfortunately, in endometriosis, many times the anatomy is distorted or contracted. If we have rectovaginal nodal, the nerves are deviated medially, the ureter, the vessels, and we have to know the normal anatomy in order to survive or succeed in this endometriosis distorted anatomy. Speaking about nerves, we have two main groups, the autonomic network that are the smallest ones, the superior hypogastric plexus that starts in the pulmontorium, then it gives the epogastric nerves, and I will show you afterwards it hands in the inferior hypogastric plexus, and we have the somatic nerves like the sacral roots, the pundenum, sciatic, and the obturator nerves. Here you can see very beautifully, thanks to the magnified eye definition vision of laparoscopy, the superior ripogastric plexus covering the prumontorium. Of course, we don't have such a nice vision, anatomical view in every patient, but if it is a thin patient, it's possible to see this mesh of nerves, autonomic innervation.

This is the left inferior hypogastric nerve, and there goes the right inferior hypogastric nerve. Speaking about the anatomy, that inferior hypogastric plexus that I will show you a video afterwards integrates the junction of this inferior hypogastric nerves that joins with the splenk nerves that are parasympathic. The epogastric are sympathetic, and it controls the urinary function, the bowel, it controls the defecatory, the prestotic movements, and of course the sexual function. So we have to be aware about that surgical risk zone that is maximum when we dissect the neutrosacral ligaments. That's why it's important to know some landmarks and relationship between these nerves and these structures. When we open also the rectovaginal space, we can damage these nerves. Speaking about the somatic nerves, and they are vulnerable, they are bigger, they are larger, but when we go for a lateral deep excision near the periformis or sacrospinals ligament, we can cause some damage in the sacros plexus.

Also, the obturator nerve risk in pelvic side wall dissection can happen if we have lateral disease, and sometimes it's not common, but it happens and it can cause relevant impairment on women quality of life that is the sciatic nerve involvement that leads to severe motor and sensory deficits. Finally, the pudendal nerve that we can reach it in the deeper rectal space or when we are close to the alcohol canal, and it is essential for urinary and fecal continence and sexual sanctions. So from now, we define this surgical strategy to avoid to use thermal injury, thermal energy with monopolar very close to the nerves because we can cause damage on them. Also, in terms of surgical strategy, we should first identify the nerves and then try to excise the disease, not the opposite, because if we know where are the nerves, we try to spare them, we try to preserve them, and of course we should map the fibrosis to prevent traction injury during the excision.

Again, another example, this is how we normally do cold seizures, simple instrument opening this perectal space. You see the ureter laterally, you see the nerves medially. We try to go as close as possible to the bowel wall, to the sigmoid wall, to the rectal wall, because like that we avoid to damage these nerves. And in this way, we keep this function that I described to you before. Here are the anatomical risk correlations, the lateral permeal excision, the sacral root infiltration, and these posterior deep lesions that are the higher risk. Anyway, we try to organize and structure these locations in order we can reduce the risks and improve the safety of our surgical approach. If you worry about this molecular drivers of neurogenic pain, we have the nerve growth factors, we have this venyloid receptors, we have the pain neuropeptides. All of them are involved in this peripheral sensitization in the neurogenic inflammation.

So the mapping of the biochemical landscape of endometriosis, it's also relevant in the process. So this is the citochines and this inflammatory environment that is associated with the pain in endometriosis. There is also some changes in the density of the nerve fibers, and this can be associated with the diseases itself with all these nerve growth factors overexpression. Also with this, you can see in this endometriotic lesion and the pathological density, this change is associated with the intensity of the pain. So there is this pathway. That's why most of the times endometriosis, the first complaints are during the menstruation, many times localized in the pelvis, in the scapula or in ... But with time, there is this transition with peripheral sensitization, with central sensitization, and the pain becomes chronic. So of course, our goal is to identify the disease at the beginning when the disease happens during the menstruation or happens during the ovulation, and it's not very, very severe.

But anyway, there is this pathway that we have to take into account because many times we have chronic, strong, severe pelvic pain that impacts severely the quality of life of these patients. Speaking about this preoperative clinical phenotyping, there are some red flags that I want to highlight. This is important to do before the surgery, because sometimes it can be related to the surgery if we didn't do a nerve sparing procedure, but if we identify it before the procedure, for example, the urinary function, and sometimes we need to do a urodynamic study before the procedure to see if there is a stress renar incontinence, incomplete bladder emptying. Also, the bowel symptoms, also the sexual function, and also the somatic signs. And we do in our center in Port, that is the biggest center, referral center in Portugal for the complex cases of endometriosis, we do it systematically.

The preoperative study also includes a good imaging and MRI. We now have this neuro MRI protocol that gives us information about the mapping of the nerves in the pelvis. And we know that after the brain, the pelvis is where there is the huge network of mesh of nerves. And more and more, the ultrasound is gaining a relevant role in this preoperative study, but also intraoperative. We do an interoperative ultrasound imaging. There is this nerve risk stratification mapping that also it's important to know and to follow high risk. And this we should present to the patients before the procedure in the informed concept, I think it's the transparency and the honesty that should take place. The multidisciplinary surgical planning, we have this in our department and in Europe and in all the countries, it's one of the criteria, including criteria to be referral center for complex endometriosis.

Coming back to the surgery, these are the principles of nervous excision, as I said. First, nerve identification. Try to navigate in these vascular planes to minimize the neurovascular injury and the thermal spread in the lateral and posterior compartments. Again, these are the risky areas, neutrosacral ligaments, parametrium, pericopos, rectovaginal septum, lateral pelvic wall. For the parametrium, we always ask our radiologists to do a very, very meticulous MRI in order we understand what is infiltration by the disease, what is endometriosis, what is nerve tissue, what is the veins.

We do radical parametrectomy in oncology. We use the same principles, but in endometriosis is even more difficult because the anatomy is more distorted and also the tissue is very freeable. These are the strategies in high-risk zones. Of course, we know for rectovaginal, we open both parectal spaces. We go in the rectovagin space, we identify the nerves in the lateral compartment. Again. This is the principle. We know that in laparoscopy or robotics, we use CO2. We have this pneumo dissection that helps a lot to work in the rectropritonium, and we use traction contraction trying to be, but the principle is to work as close as possible to the bowel to avoid the nerve injury. Again, in this image, we see the different structures that we have discussed before. Here in this view, it's very clear the inferior hypogastric nerve, ochabioxis space, ultrasocco ligament, and relationship with the ureter.

Again, this is the inferior epogastric plexus below the ureter, below the inferior uterine vein.

I think it's a matter of survival in this location to know what is the deputy vein, where is the inferior hypogastric plexus to keep the function. Again, this is another video that shows the splentic nerves, the parasympathetic ones that go to the bowel. And if we damage them, we can impair, of course, the bowel function. Again, it's time-consuming many times to identify, to spare all the nerve structures in this location, but it makes a huge difference in terms of functional outcomes for our patients. Also, we can make this intraoperative neural monitoring. As was said before, in during mark postover has worked a lot on this. There are some systems that allow us to check the function of the nerves during the procedure. It's also a bit time-consuming, but anyway, sometimes it's important. There is this concept that is very controversial about nerve reconstruction. There are some literature that says that we can use 9-0 monofilament sutures, but I'm not very convinced about it.

I think the way is to avoid damage the nerves, paying attention to thermal energy, of course, try to damage them in order to preserve the pelvic organ function. Of course, I like robotics more and more because this is the right inferior hypogastric nerve because the first surgeon, we control the scope. We zoom in, we zoom out, the picture is very stable. And then when we are working with electrosurgery like here, close to the nerve, we can be very precise and avoid any injury that can be associated with all these effects that I described before. But again, in endometriosis, sometimes the disease infiltrates the nerves. Like in this case, the nodule infiltrates the inferior hypogastric nerve on the left side. So there is this dilemma. We excise the disease and we damage the nerve or we live the disease and we keep the nerve.

Many experts and some literature says that we can do it in one side and we keep the function, but anyway, we can discuss it afterwards. There is some clinical outcomes and data review on the impact of this nerve-centric status on long-term functional recovery. And in fact, this strategy is promising, offering better outcomes to our patients. The postoperative rehabilitation also is important. More and more, we recommend the physiotherapy, pelvic neurostimulation to those patients. There is a lot of new studies on that. I know the time is finishing, that's why I'm moving a bit faster. So in conclusion, it's important to combine the phenotype, the preoperative imaging, MRI, ultrasound more and more. The functional compremary endpoints are of paramount importance. Again, where are the nerves, the location of them, and the future directions will be probably mapping more or better the nerves during the procedure, before the procedure, to keep the function and to excise the endometriosis to improve the quality of life of these women.

Thank you very much for your attention. And if you can put the last slide, just if you like or are interested in pelvic pain in port in April 16, 18, we will organize international meeting with a lot of experts and it will be very, very interesting. You are all invited. Thank you very much.