Prenatal Interventions for Fetal Urinary Tract Obstruction

Let's move on to uh my partner Jose Piro and um I know a lot of you know Jose, uh, but, uh, perhaps you, you didn't know that he actually had been in Cincinnati now for, for 8 years. Um, and, um, he came to us from Barcelona, uh, where he was the co-director of fetal Surgery program, uh, then, and I'm so glad that, uh, he, he came and joined me, uh, as a partner. Um, Jose, you want to talk about fetaltherapies. Thank you. Thank you, Fong. Thank you, everybody in the Fidel Center, and it's a pleasure for me to share uh these talks with these, uh, uh, incredible speakers today. I will share my screen right now and uh I will talk. With you about uh Perinatal intervention And what kind of surgeries we have and we offer right now in fetal in Cincinnati Fetal Center for fetal urinary tract construction babies. Jose, I love the manicy piece in here, you know, yeah, that's very appropriate. Thank you. So, the first thing is that to offer any fetal therapy, we need to make a good diagnosis and you saw before, uh, how important is uh the selection of candidates, the uh categorization of the severity, and all the details basically in the prenatal ultrasonography, looking at this keyhole sign, the bladder thickness, how much amniotic fluid we have around the baby. And finally, the fetal sex, if it's a male and potential posterior ral valves. And also the importance of doing a, a fetal MRI. Where we can also detect other anomalies, also detect urinary ascites, etc. etc. So, all these will provide uh candidates for fetal surgery, of course. And then we need to recognize what are the complications of the postnatal sequela these babies have and then target that. So, basically, as you know, we have pulmonary hypoplasia and um neonatal death because insufficient lungs. As a result of the anidramnius, then we have renal insufficiency in many cases because this obstructive neuropathy creating renal dysplasia. And finally, we have the bladder dysfunction of this distended uh uh bladder without no cycling bing. So all these are major problems for these neonates. So what are the therapeutic goals? So basically, we need to target the lungs. The kidneys and the bladder in these babies. So, We know the lungs produce lethal consequences. Kidneys produce renal insufficiency, morbidity, mortality, and also needs of transplant. And finally, the bladder can produce bladder dysfunction with infections and a lot of problems for these babies. So, to treat the lungs, we will need to restore the amniotic fluid around the baby to enhance the normal lung development. To improve the kidneys, we can to try the compression. Even many times we arrive very late because the problem starts very early in gestation. And finally, to improve the bladder, we need to some kind of let the muscle, the tetrosor for cycling contractions and better function. So for that reason, that's the goals of the therapy. We need to select very well our candidates for surgery and Doctor Ruano make a, a very, very nice explanation of that and having a contribution with this classification and the stage of these patients. But basically, to repeat a little bit is we need to base our evaluation on the bladder tap using the uh fetal urine analysis. Using the ultrasound to recognize the quality of the renal parenchyma, there is cystic dysplasia or not, and most importantly, in my opinion, the bladder refilling after the bladder tap. So, we know that when we put a needle by ultrasound guidance and we target the bladder that is distended in this fetus, so we can remove a significant amount of urine, that usually it's all urine for analysis. But also, the second benefit of this will be that we can check how this uh bladder can refill and that will provide a good, good assessment of how this baby is producing urine. So then, fetal urine tap, electrolytes, refilling, and ultrasounds, that will be our assessment of the renal function. So that provides different scenarios. So, as Doctor Ruano qualify it, so we can have a complete severe renal dysplasia without producing a urine. So we have no option to improve these kidneys at all. The only goal of the treatment will be a pulmonary survivor, save the lung by replacing the amniotic fluid. There are some places that we have a moderate borderline renal dysplasia with a long product of urine. This will be a more difficult situation because probably we'll be late on save any kidney function, but still we can save the lung and provide these babies uh the option of renal transplant if it's necessary. And finally, the better cases is when we have Almost no renal dysplasia with good production of urine, so we can theoretically uh keep safe the kidney and try to rescue the lung as well. So it's when uh derivative techniques will have a role. So, what kind of intratine procedures we have right now. So there was a big list of different uh treatments in utero that was was attempted during the last 30 years. Basically, we have different approaches. Percutaneously, we can take the urine with a bladder aspiration. We can place a shunt, we can make infusions all percutaneously. Cytoscopy will be a good option for fetal cystoscopy and ureterral catheterization or valve ablation, we will see. And finally, The open fetal surgery was tried to produce really open uh uh vesicostomy or cutaneous uteostomies. We will talk about, about that a little bit. So, in our center in Cincinnati, we have a long experience in this kind of conditions. So, so far, we have evaluated almost 500 cases and of that, we know that we will have between 25 and 30 patients every year to evaluate. That's our overall. Also, almost 40% of these patients evaluated had any kind of surgery or intervention trying to fix or improve the situation. So we did basic amniotic shunting in 61 cases, fetal cystoscopy in 20 cases. Open fetal vesicostomy was tried as a pilot study in 6 cases time ago and finally, we placed amnio ports for ermium fusion. We have 24 cases and 66 cases with serial needle amnio fusion. So this, uh, I think it's a large experience that we are reviewing right now. And then I need to say that we can put the, the, the, the urine from the bladder outside the baby with these 3 techniques when we have good preserved fetal renal function. And then when we have no urine, there is poor fetal renal function. The only way is to replace the amniotic fluid by uh needle and infusion or amnioport amnio infusion. Let's talk first about basic amniotic shunt. Probably is the technique more used, it's more feasible for many centers and many MFMs and fetal surgeons are using right now. So there are different, uh, pigtail, double pigtail or different systems to, uh, put a shunt between the bladder and the amniotic cavity. Basically, the more uh common in the market is the Rodeck, the Harrison's or Cook uh shunt, and finally, recently, the Somaex that it's more used in Europe. All these, uh, devices range from 18 gauges, 13 gauges, or, or 79 frames for the rocket that should be implanted through a trucker and push it with a cannula and then, uh, and deployed inside the, the, the, the, the bladder and the uterine cavity. So basically, I says, all the procedures are ultrasound guided and are percutaneously placed. Once the cathedral is in place, is working, voiding the, the, the bladder continuously. So we don't have the cyclic uh contraction of the, of the netrosaur because con con constantly the bladder is, is, is, is uh empty. This is a recreation how we do percutaneously by ultrasound guidance, we can place a cannula with a trucker, sharp trucker inside so we can access the bladder and then push this pigtail, the half memory shape, OK? So, half of the, of the catheter will be inside the bladder and the other half, once we remove the outside uh cannula. Deploys inside uh the amniotic cavity for uh drainage of the urine. So the initial experience showed that this uh procedure, this is pretty successful in terms of uh feasibility, so only 2% of cases were unsuccessful in, in many series. Of course, it's not the extent of complications and between 20 and 40% of cases can have, can carry a complication. And when these devices failure to restore amniotic fluid because dislodging and and other causes, we know that we will have almost 900% mortality because of the lung hypoplasia. So also, we have almost 50% of survival rate in these babies that most of them, at least half will will have end-stage renal disease. What kind of complications has been described. So this, this is a list here. So basically blockage, so inadequate soon drainage, soon migration, that's very common that babies, and fetuses can pull or can uh dislodge the, the, the shunt. Of course, after this even minimally invasive procedure, we can have preterm delivery um because from We can have urinary ascitis when the drainage is not to the amniotic cavities, to the, to the abdomen actually. We can have choramionitis and also, uh, it's described the arogenic gastroschisis in the, in the orifice of the, of the abdomen and also more commonly, probably uh abdominal or mental herniation. What about effective efficacy? So, the shuns were uh uh assessed by the Pluto trial, as Doctor Juano commented by comparing shunting versus suspected man. This, this, uh, this trial was really difficult to create because, uh, there are many, many termination of pregnancies in, in mostly in Europe that uh make it difficult to recruit patients actually was prematurely stopped because this poor recruitment, but anyway, even it was only 15 versus 16 cases, there was a trend, there was preliminary results showing an improvement in perinatal survival in these fetuses with shunt. Later, Doctor Ruano was publishing, uh, this meta-analysis, uh, collecting many articles and papers, actually was 9 only elective, uh, articles that were with enough quality to show that there still is an advantage for perinatal survival when we use the basic amniotic shunting compared with uh a conservative management. Anyway, remain uncertain if there is any help on the renal function. And, uh, and the survival and long term. What about open fetal surgery? So we know that uh in the initial uh ages of fetal surgery, Mike Harrison and Tim Crumble who published some successful uh vasostomies, uh, having only 50% neonatal mortality, but of course, Uh, the, the open approach makes a lot of limitations in terms of pre-term delivery for sure. So, there was an, an attempt, uh, like, uh, 10 years ago, uh, by Doctor Cromer home here in Cincinnati and Doctor Lim to, uh, recreate that surgery with experience in open fetal surgery and the, and the, the better technology to create fetal physicostomy by open approach. So this is a video where you can see the umbilical cord insertion. So just below with a minimal exposure in the uterus, you can attempt to create a hole in the abdominal wall and then marsupalize the bladder for complete drainage of this distended bladder. You can see here, completely drainage of this bladder in utero and then allow these babies to close spontaneously the vesicostomy postnatally. So there are different considerations about this. There's no doubt that there is the most definitive decompression of the urinary tract. Probably can be considered uh in the urethral tricia, but uh for sure, it should be only considered when there is still a preserved good prenatal prognosis and good kidneys. Of course, the problems is that you need a deep general anesthesia. It's very invasive. You need a maternal laparotomy and hysterotomy, and of course, there is more increased maternal and fetal risk with more prematurity, no question. So the previous experience here was 6 fetuses with posteriorral buds, early ingestation, all male with a normal karyotype and in situation of honey dryness but without evidence of dysplasia and with normal urine in, in electrolytes in the bladder tub. So, there was clearly a complete decompression in these, in these babies in the, in the post-operative uh controls in the ultrasound. That's no question as well, but the results were not great. There was no maternal complications that's reassuring and the stage of this month were only 3 days in the hospital, but of the 6 cases, only 2 survivors were obtained. Basically, because, uh, uh, problems with, uh, fetal surgery and premature delivery. So that was abandoned until potentially this vesicostomies can be done with a minimally invasive surgery, maybe by fetoscopy, but we are looking obviously for other less invasive uh procedures like fetoscopic surgery, basically creating fetal cystoscopy. So you can, I can recreate here this graphic that one who put trying to access depocere urethra and the valves. Basically, the problem we have with fetal cystoscopy to attempt this posteriurethral valves is the angulation we have. We can access very well the bladder, but sometimes if the, with the rigid, uh, cystoscope, it's very difficult to see, well, the orientation in the, in the, in the posteriorral valves, uh. Uh, during the surgery. So there are two main methods, percutaneously, OK? That is the most common and also, as we do in Cincinnati, we do a mini laparotomy to assist better, uh, uh, approach to the baby. So we can place a couple of tea fasteners inside the bladder to pull all the, uh, to attach all the Layers and to pull the bladder so we can put the scope in between these two T fasteners in the dome of the bladder trying to face more straight these posteriorral valves. So you can see here how we place the T fastener here when we can pull and put the scope just in between orientated much better to the uh to the posteriorral valves. As you saw before, fetal cystoscopy is a diagnostic method, so we can differentiate if there are above, there is no patency with retro atricia or eventually Prunebelli. So that's diagnostic, but not only that, it's also therapeutic in the same procedure. For instance, this case was uh tried to attempt to look for patency in the posterior reral valve, in the posterior reter this dilatation, and there was nutrition, there was no patency. So at the same time, we can use this access to place a basic amniotic shunt and drain this bladder. Again, can be therapeutic if we see that this, uh, valves there and we can attempt to make valve ablation trying to open the patency of the urethra based on the laser, on the laser. So of course, what we expect to see, this is a newborn, uh, it's a, it's an image from uh Doctor Marciio Miranda in Brazil that always, it's very interesting because you can see the posteriorral, uh, uh, dilatation and this is what we expect to see. This is the folly pushing the retal valves. So you can see the obstruction is here, OK? So all this area is actually blocked by the valves. So this is what we expect to see in the fetus. And this is what we see, right? So we see the posterior retra distended and then the valves, and so we can burn, as you see before in the video of the Toruano, that we can very carefully. Burn these, uh, valves and make an opening. Of course, the problem is that if you have not good orientation, not good angulation, so you can make a hole through the rectum and create a retro rectal fistula or go to the perineum and create an open fistula and not to the, to the real actual pennies. So for that reason, orientation is, is very important. The goal is to fulgurate these valves and maintain open this, this urethra. So, his publications initially in 23 cases demonstrated that the survival uh with this technique reached 60% in versus the control is only 10%. But all the things that we can do and we do uh uh in Cincinnati as well is transurethral catheterization of posteriorterral valves. So, for instance, this case, it's a 22 week uh baby with severe oligodramius. It's a posterior urethral vass, uh, here detected with this keyhole image and also pretty good preservation of the, of the kidneys parenchyma. So after, uh, extensive counseling, patient elected cytoscopic surgery. So, because this was a 23 week gestation, this is the posterior retra, it's extended. We had not pretty good orientation or because the valves were up there and because we were not very confident to do a successful laser treatment, we decided to pass a wire and then we checked there was a patency, OK. There was not an attricia. So the final decision was to put a transurethral catheter, OK. So double J that we can push from the same uh axis. You can see here. And finally, we can deploy. Inside the bladder and through the penis inside the amniotic cavity. So this transurethral double J catheter was performed at 23 weeks. There was no maternal fetal complications. The fluid in the bladder normalizing also around the baby and all the urinary tract was decompressed. So this baby delivered at 37 weeks with a good weight, urinating with a pretty good kidney function, no dialysis was required and is so far doing a normal development. So, of course, it was a successful treatment and that encouraged us to use sometimes in combination with laser. So this case, we did a, a catheterization with the wire, OK? Then after check that we have access to the valves, we laser it, OK? We make an opening, you can see here. And finally, we pass again the, the wire and we deploy it, the transurethral catheter as a second treatment in combination with the laser. So we need to talk about uh efficacy. So this uh work again from Dr. Ruano compared 111 fetuses, 34, where a phytocystoscopy, 16 BA shunt, and 61, no intervention. And we can see the survival is higher in the phytocystoscopy, still high with the uh physical music shunt and very low without intervention. OK. So our expectation is that uh the fetal cystoscopy in some way could prevent impairment of the renal function, uh, and mostly prevent the bladder uh complications because this cycling, uh, voiding of the bladder that can help. Anyway, the proposal is to do a randomized control trial comparing the fetal cystoscopy and the vesic amniotic shunt because we need to compare if there's any, any advantage in each of them. And recently also the group in Paris, uh, from EBI so published 48 procedures in 33 patients, OK? And then the survival for the shunt was 83% for the cystoscopy, 92% and the chronic disease was obviously almost half in these babies. So they don't found any significant difference uh between cystoscopy and shunt, OK, but they were optimistic, uh, in the, in the cystoscopy results. So in summary, so very few cases to date, uh, not all, all are successful, of course. Uh, the cytoscopic ablation of, uh, serethral valves with a catheterization may improve pulmonary outcome and maybe renal sequela and bladder function. We need to do early detection and select very well the, the patients, of course, and of course, retro attrition and COA uh will require different management. And I will end saying that the other kind of obstruction is when we detect an ureterocele that can prolapse through the posterior ureter. Even in, in, in females can go out to the ureter, to the outside. And these are described that there is the possibility to access by photoscopy and then do, uh, uh, like we say, colander puncturing or, or laser incision in this, uh, in this, uh, cystic uh ureteroceles to decompress the, the, the cyst and allow, uh, uh, avoid the obstruction in the urethra and laser was used 20 years ago and first described by Quintero in this publication already. So what happens when we have bad kidneys, we have kidney dysplasia and minimal urine production, so we can offer this kind of derivative surgeries. So the only option is trying to rescue the lungs by placing fluid from outside, OK? So they are not candidates for shunt, for cystoscopy. So with motivated parents, we can restore the amniotic fluid and try a pulmonary survivor. What are the methods we have? So we have the possibility with needle to do repeated uh on serial am infusions, OK? And that will need once a week initially and probably twice a week in the late station and this is the way to replace, but obviously with maybe between 10 and 20 injections. The other option that we offer in Cincinnati, and we will talk in, in the next web seminars about this, but very briefly, is the possibility of placing an amnio port. The AMNO port is a, a, a portacat, a midi port that we use for, uh, sorry, we use, usually for, uh, for medication, intravascular medication. And uh parental nutrition as well that we can implant inside the uterus. So the idea is to implant this port underneath the skin of mom so we can access very easily underneath the skin every time we want for replacement of fluid. So basically, what we do is to implant with a peel away uh inside the uterus, this, uh, this catheter and then to a little wet cell closer and pass the catheter to the, the, the, the ribs of mom, OK? Usually in the left side, we can implant this uh device, this Mediport for easy access. And this is what happens before and after the amnio infusions, so we can repopulate the fluid very easily. So in terms of efficacy, it's a very new therapy, uh, uh, with the AI port, and there is only one publication from our group, uh, uh, leaded by, uh, our, uh, uh, lovely, uh, Will Passing that, uh, was very, very involved in this kind of therapies and, uh, the AMI report in this report was performed in 8. Patients and we can say that uh there was uh successful restoration and maintenance of the amniotic fluid in all 6 and 08 and six of them had pulmonary uh uh none of these six have pulmonary hypoplasia besides two that died, one because and recognized laryngeal web and another for pulmonary hyperplasia after early delivery. So now we have 24 AMNIO ports in Cincinnati and we will review soon and hopefully we can update you guys. And I finished my talk saying these different messages. So in another intervention for fetal uh obstructive, uh, urin urinary obstruction should be only undertaken in special license centers. It's very, very specific treatment and we, you need to be expertise in the field to avoid significant morbidity that you can generate. So, I hope that in the future with new technology, new shuns, probably Valvet and novel photoscopies, uh, we will help to be more effi uh efficient and with fewer complications. Finally, it's mandatory and essential patient selection to ensure the intervention is only performed where benefits overweigh the risk and also use perfectly well the intervention window. A late intervention may be not as beneficial. As others. And then finally, we need to recognize that, not all cases will need fetal intervention and for that reason, this selection is important to have a very good diagnosis, very good multidisciplinary team to approach these, uh, cases in specialized centers. So, still remains a lot to do in this field, and functional imaging, biomarkers, randomized control trials, technology, etc. etc. and hopefully in the few years, we can provide better solutions for these little babies. Thank you. Thank you very much. Thank you, Doctor Pera. That was a wonderful talk. Um, a question came through the chat for, was mentioned by both you and by Doctor Duduano, um, talking about the bladder refilling after vesicocentesis. Um, and the question was whether the volume, uh, that refills the bladder is important prognostic or diagnostic information. Do either of you mind mentioning that? Yeah, so, so basically what um What we need is to replace the volume in the amniotic cavity that we know the turnover is very fast, OK? So, if we don't maintain a significant amount of normal amniotic fluid, the lungs will still be hypoplastic. So for that reason, it's very important to make a, uh, uh, a very serial and frequent uh population of the fluid around the baby, and that's why we started using the amnio port to have better access. Otherwise, you will have no successful, uh, replacement. Yeah, you asked about also uh Stephanie uh about bladder refilling, is that right? Yes, after bladder tap. Yes, after we do the vesicocentesis, we had a publication that we, we studied that. Uh, after we do vesicocentesis, 48 hours, we established 48 hours. There was a discussion about 24, 48 hours, so we decided in 48 hours to make it easier for us and then to avoid multiple, uh, recent taps. And while the cutoff that we saw, we use, um, uh, we measure the volume of the fluid inside the bladder. Uh, before we tap and after, uh, 48 hours after, and then the, the cutoff value was if the volume becomes, uh, at least 40% or more, so the cutoff was 40%, uh, then, uh, we, we had a good, uh, indication that, uh, the shunt or the cystoscopy could, could work. Great. Thank you very much.