Fetal Intervention for Lower Urinary Tract Obstruction

Um, but first of all, I like, um, Doctor Rodrigo Ruano, my friend, to kick off, uh, the, the session for today. And, uh, a lot of you, uh, know Rodrigo, and he is a longtime friend. He's currently, uh, a professor of obstetrics, gynecology and reproductive Sciences in McGovern Medical School at University of Texas Health Science Center Houston. He's also the co-director of the Vital Center at Children's Memorial Herman Hospital in Houston, Texas. And in the last 5 years, uh, he actually was the, um, MFM chair at Mayo Clinic. Um, and as you all know, um, he had co-authored many, uh, peer-reviewed articles, I believe now maybe close to 250, 300, uh, and also more than 50 book chapters. So without further ado, I'd like um to invite my friend Rodrigo to kick this off. Rodrigo, thank you, Fong, for the introduction. Uh thank you, Jose Luis Pero, and thank you, Fong, for inviting me for this uh this special uh uh discussion and discussing about uh neuropathic, uh, in fetuses, uh, which is really my, um, my passion. Uh, and I'm going to, uh, share my slides. I'm going to talk about uh prenatal diagnosis, uh, um, uh, but I, I'm going to focus on something new because I have only some 2030 minutes to discuss about that. I'm going to discuss about uh how can we uh uh stage the disease, uh, uh, during the prenatal care, and then how can we, um, uh, use the staging system to manage or to um manage specifically those babies in utero. So, uh, the title will be Fittal Intervention for Lower renal tract Obstruction based on a prenatal staging System. So I, I don't have any conflict of interest. Uh, first, we need to talk quickly about etiology. When we talk about the bladder obstructions, outlet obstructions, or lower retract obstructions. Uh, we are talking about different diseases. The most frequent disease is posturethral valves that we see more often, uh, postnatally, but the pain in the gestation age, if we see it, for example, 12 weeks, maybe we can, we can, uh, we can face different diseases like uh urethroresia, which is more severe, which are more severe and more severe, and an urethral stenosis that can be more mild. And then we have different other disease, for example, Prunibeti syndrome. Which for me is a genetic disease that you don't have a re-obstruction, but you have a weakness in the muscles and the bladder and the abdominal and the abdomen and then uh those uh fetuses, they will have a distended bladder, even sometimes the keyhole sign and then a bilateral hydronephrosis, but the amount of fluid will be normal or even increased, which is different than the pretty bad features that can be secondary to an obstruction. So when we have uh an obstruction early on in pregnancy, then of course we can have overextension of the bladder and the belly and abdominal wall, and we can cause weakness of the muscles and we can have also the same uh features that we call prebtic features, but we have rare diseases that we can have an urethral valves or mega urethra when we have an obstruction. At the end of the urethra or uh proximal urethra and urethra. And we have, sometimes we can have prolapsed urethroceles, which I have seen most often in female fetuses that uh we have an, an uh urethrocele that can uh prolapse into the urethra and can cause an obstruction. And we have cloicogenesis more often also in female fetusesis. But so it's very difficult. So we are talking about different diseases. That's why they allude to terminology for me is very interesting because we are talking about all of those problems. And the incidence, the importance of that's that whenever somebody may, may, may, may, may say that the incidence is very low, but I think the majority of those babies, they don't make it to the postnatal uh life. Because the mortality, if we have an obstruction uh complete obstruction before 24, 22, 24 weeks, we are going to have any hydramus and by consequence, you're going to have severe pulmonary hypoplasia, and those babies, they, they are born and they die. Or we know nowadays, and many of those patients, they opt for selective termination of pregnancy. And then, um, those babies who survive, which is less than 10% in our population. Uh, that's why the incidence may be higher than that. Uh, then, uh, they will have bad renal function or they are going to have renal function impairment, and some of them, the majority of them, will need dialysis, renal dialysis and transplant, which is very complex for those babies. So, the diagnosis, usually, we make the diagnosis during a fetal anatomy scan during the At, during the second trimester, 1820, 22 weeks, and we usually, we can see a distended bladder with the uh bladder wall thickness. And then we have the standard posterior dilated posturethra, that we call the keyhole sign. So this is very characteristic of luo obstruction, but again, this does not specify the, the cause of the disease, the, the, the etiology. And then we are going to see bilateral renal hydronephrosis. And then uh nowadays, we are seeing more often, if you do an early ultrasound at 1214 weeks, 1114 weeks, we can see the megacysts during the first trimester, which we know those cases are associated with more severe forms of obstruction, maybe erythrophias or other diseases, or more, even more often associated with the uh chromosomal or other structural anomalies. And then, uh, the geology of the problem cannot be, uh, diagnosed or determined by ultrasound or MRI, and that's why I think the phytocystos phytocystoscopy can play a role because we can put a tiny cystoscope inside the bladder and then we can try to identify the cause of the obstructions as I'm going to see in a few minutes, show you in a few minutes, uh, and then we can, at the same time, we can treat. So fetocystoscopy can be a diagnostic tool. That's why I'm, I, I'm, um. I'm discussing in this uh lecture and Jose Luis, we will speak a little bit more after, uh, the, uh, after this, uh, and also can be at the same time we can use the cystoscope to guide our treatment. So, After discussing about diagnosis, we need to talk about prognosis. So, how bad does this, uh, the obstruction is for this fetus. Of course, we have associated anomaly, heart anomaly or congenital chromosomal abnormality. This is more severe. So, Uh, that means that the first, uh, evaluation of all fetuses with, of fetus with Luto is, uh, is to do a multidisciplinary approach. Then we need to have an ultrasound, we need to have a genetic counselor and possibly genetic analysis, and we need to have a fetal echocardiogram. So, and then once we have all those, the, all that information, then we can classify if we have just An isolated luto mean, meaning that we excluded cardiac or other structural anomalies or chromosomal or genetic anomalies. So we are dealing mainly with the isolated lute. Of course, some of those babies, they may have gastrointestinal anomalies too that's very hard to see, to diagnose early pregnancy and even sometimes late in pregnancy. But then, when I'm considering luto, isolated luto, I, I focus on the ultrasound findings of the kidneys. Uh, and the fluid. So if we have oligohydramus. After 18 weeks. Everything that I'm talking here is after 18 weeks because before 14 weeks, the only thing that we can do is do the ultrasound, uh, appearance of the kidneys. But if you have oligohydrams or anhydrams after 18 weeks, before, before 18 weeks, the placenta may produce some, some fluid. So it's very challenging that you consider only the, the fluid, uh, uh, uh, before 18 weeks. But if you have hyper renal cortex, that means that some of the, the kidneys are ready, uh, the renal tissues are ready. Uh, uh, uh, affected. And then we can have severe hydronephrosis that many people are saying that's not, does not correlate with prognosis, but then we have cortical cysts, and then if we keep, uh, watching the situation without treatment, we can have progression to renal dysplasia. And then, uh, the other thing that's very important to me is the bladder volume or bladder refilling after we tap the bladder. So many people ask me if I do the biochemistry, yes, I use the bio biochemistry as a complementary to the ultrasound. So I, I tap the bladder, uh, and, and I do biochemistries, uh, the main, main simple things and we classify if they are favorable or not. And then if it's not, then I, I see, I do another tap in 48 hours to evaluate the bladder refilling and also the biochemistry again. I do maximum 3 times. And if the bladder is refilling well and if there is an improvement, if the, the biochemistry get is getting improved. Then I, I can offer the treatment with a different concept. So everything that I'm talking is to present this, which I think is very new, uh, and I have been fighting for this. I think the most important, uh, step if uh even before we compare the type of the treatment, feettocystosco versus vas vascomuniotic shunt, I think the most important to understand. Uh, which stage of the bladder obstruction are we are facing now. So we classify based on experience in different stages, initially on three-stage, but now we are classifying 4 stage. So stage one is then after 18 weeks when we have normal fluids. And, uh, amniotic fluid and also when you do the ultrasound, the kidneys are just hydronephrotic, but there is no hyper, they are not hyperchoic or they are not, we, we don't see cysts or we don't see any signs of early stage of renal dysplasia. Uh, uh, for this situation. If you tap the bladder, the biochemistry will be fine or progressively it will be favorable. And then uh there's, for us, there's no need to treat this group. Why? Because the fluid is fine, so there's no risk of pulmonary hypoplasia, which is the main objective of the intervention in utero. And secondly, maybe those cases they have a partial obstruction so the kidneys are not under strong pressure that can cause renal tissue damage. So what we can do for this case is a weekly ultrasound. And if you progress your situation, the, the fluids coming down, I don't wait until to be any hydros it start getting down, so then we are seeing oligohydrams or we are seeing brightness. Kidneys are bright and hypeechoic. Or we are going to start seeing some cysts in the cortex, then we are progressing to stage 2, and then if we tap the bladder, we are going, still going to see limited or favorable biochemistry and then if we, we see this patient in 48 hours, the bladder refs well. So the kidneys are producing urine and probably with a good um um uh good quality. So in this situation, if it intervene. is indicated to, of course, prevent pulmonary hypoplasia, but also to prevent end-stage renal disease or renal impairment and dialysis transplant. But we have another situation that uh the, the, the, we have uh olicohydramus or anhydrams after 18 weeks, the same that we see in stage two, but now we are seeing some renal, some signs of renal dysplasia or some cysts in the cortex. And then there's a decreased amount of fluid, and then when we tap the bladder, the biochemistry is not favorable. And then, but there is some rethinning of the bladder, there's still some rethinning of the bladder. So this situation. Fit intervention is not indicated to uh improve the kidney disease, but uh it's, it's important to, to discuss with the patient and possibly we can put a shunt there and to make the fluid uh better and then develop a live the lungs. So this is under investigation for me, but I, I, that's why I put lots of question marks here. But then later, we identified a very interesting uh situation that we are already seeing intrauterine feto renal failure or end-stage renal disease in utero. So then we have ultrasound signs of renal dysplasia, which we do a microscopic analysis of the kidney. We get the kidney and a, and take a look and cut. We are going to see this. Same uh uh uh uh features. And then we have a mildly dilated bladder, so the bladder is not dilated anymore, but, uh, the, the wall is thick. So many people will say, no, this is a multicystic renal dysplasia, no, this is, uh, uh, polycystic renal dysplasia, sorry, no, these are multicystic kidneys caused by renal dysplasia, may be caused by an obstruction. And then we have progressively decreasing amount of amniotic fluid. So that's why it's very important to, to follow those patients weekly. And then, uh, the, uh, the outcome is very poor. We, it's, uh, this situation is associated with neonatal death within 24 hours after birth, and, and also, uh, end-stage renal renal disease, meaning dialysis within 1 week of life. And these are the images I would like to share with you. So we have this kidney or these kidneys like the lots of cysts and the like we call it, which is renal dysplasia. And then this is the bladder. We have a mildly distended bladder with a thick wall, and then we still can, if you pay attention, we can still see the dilated pus urethra. So we have the keyhole sign issue. So this is a stage 4 for uh intrauterine fitorrenal failure. And then we believe, of course, that's a progression, progression of the disease. So we can start with stage 123, and 4. But sometimes when we do the ultrasound, it's already too late because we didn't have the opportunity to follow these patients before. So speaking about treatment, Jose Luis will speak very carefully about those treatments. We have vascommunal shunt and we have cystoscopy. And the medication in the past was to uh offer uh these treatments, even when we start this classification was you offer for stage two to try to prevent, uh, uh, pulmonary, severe pulmonary hypoplasia, but also to try to prevent end stage renal disease. So those are the objectives, but nowadays we're discussing different options. Uh, if we consider the staging system, as we are going to discuss. And then, uh, the treatment, of course, is based on the nature history. If we have a prenatal mortality higher than 80, 90% with, because of pulmonary hypoplasia, and we have a severe morbidity for those who, who survived. Uh, or renal failure and also bladder function, that's something that we're investigating now. So the question that, uh, I let, uh, Jose Luis, uh, discuss about that, if it's, if, uh, a fetal intervention really improved the, the, or changed the natural history for, of Pluto. But, uh, and then, uh, this is, uh, uh, a Pluto trial, the Pluto trial that everybody knows, and I wanted to bring this here quickly because many people have different conclusions about this study. But this study was interrupted early because of a difficulty in recruitment. And this study was published in The Lancet just because uh it shows it was a very well analysis, a very, very good analysis, very well conducted, but it shows how difficult is to perform a randomized control trial in a rare, very rare disease like this. And the mainly difficult was to recruit those patients becau and also To keep those patients in each arm. So some patients were allocated to receive the treatment, vascommunal shunt, but then they decided to move. 3 of them of 16 decided to go to the other arm, which was expectant management. And within the expectant management, some patients decided to, to go to the other arm, so it was very difficult to conclude that the study was stopped earlier. So if you do an intention to treat analysis, which would be the best way to analyze the randomized controlled trial, there was no difference, but they were crossed, uh, the, the arms was uh they crossed. So if you do the, uh, treated analysis, then you could see a real uh improvement survival rate for those kids that had treatment. But the, um, the number of cases were not as enough, uh, were good enough to show some changes in the renal or the, in the prevention of renal. Uh, changed because of the, again, the sample size and also there was no classification of the staging system. And then a secondary analysis, uh, Doctor Kirby's, uh, Kirby's, uh, uh, group showed that uh there were some factors that were associated with the prognosis, so showing that the staging system is important prenatally. So that's why I'm bringing that study to bring back that. And then we have the fetal cystoscopy. There can be a diagnostic too. So if we put a scope inside the bladder, we do different than a the urologist postnatally because they do retro retrograde study and we do enterograde from the bladder to outside. And then we, if we advance a scope inside the dilated posturethra, we can see uh, uh, an obstruction, sometimes a, a type of a membrane or sometimes the, the uh very classic posturethral valves, and then when we do this, uh, we can touch with a laser and we can try to open with a laser, and then if it does open, the bladder empties and then Allows recycling the, the, of the uh of the bladder and also allows for the, the more natural uh uh release of the urine in this situation. But we can have different diseases as I mentioned before. We can have an uh narrowed, uh, urethra, then we have urethral stenosis and sometimes depending of the, the narrowing, uh, situation, this can be a We can put, it can be more obstructive and sometimes we can put a catheter inside the urethra, the urethra, uh to try to, to improve the, the situation, or we can have a very tough situation that we have urethra atresia. There's no continuance of the urethra, so the urethra is, is, uh, stopped, and then, uh, we try to, to see if there is any way to conduct to the the urethra, uh, uh, in the penis, but we don't. So this situation for us is more difficult and we need to stop this, the scope and maybe discuss with the patient either place a shunt or some people, they, they, they discuss about termination because the prognosis is not very good. So this is an example of a cystoscopy that we do. So initially I, I, I do it under local anesthesia and then um. And we do a, a local sedation. And then we do a local sedation to the, to the fetus and then uh we introduce a tiny telescope inside the bladder. We uh we identify the, the obstruction, which is the diagnosis. And then once we find out the obstruction, we use the laser fiber, uh, the laser, uh, very tiny laser fiber to, uh, to, uh, open, uh, the, the, the valves. And I think Jose Luis will show this more, uh, in more details. And then once he empty, we open that, the bladder gets emptied, uh, is, uh, empties, and then we can see even the flow through the, through the urethra. And then that improves the amount of fluid, improves the, the, uh, release the pressure inside the kidneys, and then, uh, uh, preventing, uh, uh, pulmonary hypo uh hypoplasia and then a renal impairment. And then, um, um. We had a proposal, we had a long discussion before, but we have a proposal to do even fetal cystoscopy at 16 weeks for mega cysts uh diagnosed at 11 or 14 weeks, which is important before we do the cystoscopy to have another phyto ultrasound at around 16 weeks to see if the bladder is due. Uh, big, and we, we recommend uh a CVS at 1114 weeks and early fetal echocardiogram, trying to, to, uh, uh, uh, exclude or rule out some of the associated anomalies. If we have presence of associated anomalies, then it's a more complicated situation. But if you don't have any anomalies and we're talking about isolated lutu, even though we, we have about 40% chance of having other problems as well as like urethroresia or even uh mega bladder microcolo intestinal hyperitis uh syndrome, which is a very severe disease. And nowadays we are seeing, we are treating those babies, so we are seeing babies with a good bladder, good kidneys, and even with good lungs, but they are having more problems, uh, more problems with the bowel or the intestine. So just to discuss a little bit about uh interventions. So, uh, uh, this is a study that we did with 111 fetuses in the, uh, with other centers. And then we compare cystoscopy, vascom shunt and no intervention. This, of course, was biased because no fetal intervention was those uh were uh were those patients that we didn't think it was severe, but, uh, and then if you see the survival rate was, uh, a little bit higher, was statistically significant, was higher in the group of fetocystoscopy when compared to shunts and when compared to no interventions. And then people say, well, that's because the cystoscopy is important. No, the, the real reason was that the disease behind that, and cystoscopy was able to help us to diagnose that. When we have urethral valves, for example, we treat all of them with cystoscopy, and they, and the survival rate and the, and the renal function was better after treatment than compared to what's going on the treatment, of course. But when we have uh atria, the prognosis is not good in, in any of them. And then, um, uh, uh, some patients we have vaso uh vasourethro urethral reflux, and then, of course, the prognosis was good even without treatment. So treatment is very important. That's why I think fetos cystoscopy made a, a difference in this group. And then the people will say, well, let's use fetocystosterone to everybody, but fetos cystoscopy is associated with some problems. Um, one of the problems uro uh urological fistulas that depends on the, on the technique that we are using. So we, we need, we need to have, uh, to immobilize the fetus to avoid movement that can cause more damage if you use the laser. We need, we really need to use a curved scope that we can have a, uh adequate curvature to go and to identify the obstruction. Of the, of the in the urethra and then work on that and we definitely need to use less energy and less power in the laser fiber. I know, um, that's a question from, uh, Doctor, um, Mohan Ibrahim from India about, uh, which kind of scope do you use? Do you use flexible scope for your laser? Yeah, so that's a good question. So I use a semi semi rigid scope, uh, 1.3, and, uh, and also a flexoscope, and I'm using a new scope that has a very strong, good curvature from towards you. So yeah, so, uh, a flexible scope as, uh sometimes I use too, but I'm using more semi rigid scope with a good curvature. Thank you. And then just that you have um um um you have some outcomes about fetocystoscopy. Uh, the accuracy diagnosis etiology of LO in our series, uh, among 35 cases, we were going to diagnose the correct, the, the, uh, uh, cause of the Luton in 91% of the case. Then, uh, we just did laser for posturethral valves, and then we observed the recurrence of the bladder outlet obstruction, 20%. And some of them we tried to do another laser so that we learned that it's better not to do that. So we don't recommend to do a second laser if the first laser failure. Uh, failed because then we can have, uh, yeah, re, urinary fistulas, but, uh, the survival rate in our series was about 55% in two years and then 73% had normal renal function, which means no end-stage renal disease, no diazemal transplant. OK. And then, of course, you can use the, the shunt, but the shunt has lots of complications such as migration and blockage. So we need to follow weekly, and the survival rate uh here in the United States was higher with the the renal function was similar, uh, when we use cystoscopy, but the reason for that is that we use that staging system. So we just treated about 30-40% of our cases that really didn't had uh stage two disease and also we, we, we, we follow those patients very closely, weekly, and once the shunt was out, we replaced the shunt. So that's the reason that the survival rate was a little higher. And then I compare cystoscopy and a and a shunt. The main advantage of cystoscopy is that we can diagnose the cause of the disease and we can also uh treat specifically the cause of the disease. And some people are saying that this, uh, this treatment is more physiological for the, to the bladder that we can have a more physiological bladder decom decom de compression, and then we can have, uh, the the bladder can, can cycle. Uh, but it's more invasive. It has risk for problem maybe higher because we are using, uh, bigger instruments, a little bit longer. Uh, prematurity, we don't know much, but it looks like it's 25% of a series. Uh technical, technically is more challenging. So, uh we have a proposal that uh we can either offer uh fetal cystoscopy for the patient, and then if we see urethral, postureurethral valves, valves that for, for, so the fetal cystoscopy is a diagnostic too again. And then if you see posturethral valves, we do laser figuration. Uh, I think that, uh, and sometimes if, if we think we can put a catheter in the urethra. And then if you see urethra stenosis, we just put a, a catheter inside the urethra. And then if you see urethraatresia, then we don't attempt to do laser, we just stop and then we discuss as a shunt or uh something else. Or we can just go for phyto uh vasicom shunt and postnatally, uh, the neurologist can uh deal with the treatment, uh, with a a specific treatment for the cause. And, but the most important, again, uh, the concept is that if we have a stage 1 LUO, the prognosis usually is good because no risk of a pulmonary hypoplasia, a minimal risk of end-stage renal disease. So we just, uh, uh, uh, our, our management is expectant. And then uh we do a weekly ultrasound follow-ups. And then if you progress to stage 2, then we, we recommend for this group, uh, fetocystoscopy. That's what we are doing first or vag gonna be not shunt. For stage 3, we, uh, is, uh, the kidneys are not producing good quality of Uh, of urine, but I produce some urine, so we we recommend vasomal shunt and maybe later um infusions. That's the difference between uh the many centers. And stage 4, there's no production of urine anymore, so that's the end-stage renal disease. We go from the ceremony infusions and we are part of the RAFT trial. So, So this is just an example that I'd like to share that this baby was born after some treatments. We diagnosed the obstruction at 17 weeks. Uh, this baby, maybe many people would say that has a pruny belly uh syndrome because it has a pruy belly, uh, features here, uh, the testicles, you know, descend. I had also some club, club foot here, uh, but in reality, this baby had a very large, large bladder, oligohydrams already 1718 weeks. Cardiac was compressed, so the baby was almost dying. They had some even fluids in the pericardial effusion. And then when we did the scope, we saw an urethral fusion and we put shunt. This patient needed 34 shunts, delivered 34 weeks, and the baby is doing fine. Now, the baby is 88 years old, has normal blood, has normal kidneys, and norm normal uh lungs, normal brain. Development, but it still has a cystoscopy because the, the urethra is very abnormal. So, but the kidneys, the lungs, and the brain are normal. Just the bladder has a cystoscopy and a, a cystostomy, sorry, cystostomy, and she needs uh some treatment. So thank you again for inviting me and I'll be happy to answer some questions. Thank you, Rodrigo. Um, and questions are actually for both you and also Jose since you all both will be talking about fetherapy, uh, Jose will be talking about fetaltherapy as well. So, um, there are 3 questions. The first one, how do you mobilize the fetus during cystoscopy? Um, the second is how do you, uh, prevent chorion amnion separation during this, uh, procedures? Yeah, those are good questions for me. So I, I don't do an infusion before the cystoscopy. So that's another advantage of a fetal cystoscopy, uh, because I don't do an infusions, so I, I, I, I enter the scope directly to the fetal, uh, bladder. So usually I don't see, um, uh, chum separation because I don't do, uh, much, uh, amnio uh infusion. Uh, what I, uh, so then once I, I, I don't mobilize the fetus tube because sometimes it's difficult to, you don't have a space. I just plan to entry, uh, I, I need to have a three-dimensional view of, um, the situation. I, I plan to have the scope, um. Uh, let me see if I can show that image. So I try to enter it with a scope very high in the bladder to have the adequate curvature, and then I plan to have the adequate curvature. So that's the way that I do. Um, um, um, the difficulty here sometimes that the bladder needs to keep, uh, uh, full. Uh you need to maintain the bladder extended in order for you to, to keep uh uh performing the, the, the cystoscopy. Uh, the main risk that I have seen with the cystoscopy sometimes is gastro, gastroschis-like disease than a coin separation. So then sometimes some of those babies, they need treatment afterwards. Need to answer your questions? I don't know if you answered the questions for our audience, but, uh, definitely it's um not as simple as you have mentioned there. Um, you want to you want to chime in and then we will move on to uh Maria. Alright, Jose, you want to say a few things about that, or can you hear us? Well, I can comment about that. Some, some different things we do in, in Cincinnati for a little better position of the baby and the bladder, but I will comment during the talk and Extend more than that. All right, great, um.