Global Multidisciplinary Initiative for PUV

Next, uh, speaker is Massimo Gariboli. He graduated in medicine at the University Vita Salute San Rafale. I'm sure I butchered that. In Milan in 2003, he was trained in pediatric surgery and pediatric urology in both Italy and Spain, and undertook a two-year fellowship in. Pediatric urology at Great Ormond Street Hospital. He's now a consultant pediatric urologist at Evelina London Children's Hospital and Guy in Saint Thomas NHS Foundation Trust and is an honorary senior lecturer at King's College in London. Thank you very much, Doctor Garariboli, for joining us today. Thank you very much and uh thank you very much for the invitation. It's, uh, it's a very great honor for me being here today. And uh I hope that uh after such a high-quality presentation from my colleagues, I will not um be too bad. Um, so let me just uh share my screen. Uh, I'd like to, uh, take this, uh, topic in a different perspective. Um, of course, so when we talk about an, an history, we need to start from the very beginning of the history. I need to thank some great people. Uh, Mugani was the first one who In the 70, uh was uh mentioning something related to valve, but then it took almost uh uh two centuries before there was a real uh breakthrough with uh um Young who actually made a lot of uh impact, describing more analytically and also giving us a classification of the valves which in some way, we are still adopting. Um, another part of the story is to understand how we have reached to the point. Of course, we have heard a lot today about how to intervene, but, uh, it is important to understand how the valves create, what is the mechanism neurologically that, uh, bring to the the patient having the valve. And of course, the development of the, of the embryo, um, Uh, start from the, from the very, very early weeks of gestian line, and what is very important that we focus on which is related to the valve is two main structures, the, um, the mesonephron and, and this, uh, urogenital sinus formation with uh uh the um formation and the development of the lower tract of the urinary part. And why this is important? Because what is the theory behind the formation of the valve? There are not a unique, uh, type of theory. There are 22 main, uh, theory which suggests that uh could be uh a malformation of the end part of the Wolffian duct or the mesonic duct which then generate the valve. Or another theory that has been proposed is that there is a sort of a membrane that is created, uh, in the posterior urethra. So now I'm telling you another story. That's the story of Michael, which is a patient that I first met when he was 26 weeks gestational age, and you've heard a lot from Doctor Ruano and Topero about what it means having a diagnosis antenatally of valve. Uh, the second time I met him was after his birth, and once again, we have learned about how to understand the diagnosis of the valve based on uh BCOG or MCOG and ultrasound scan. Following the diagnosis was confirmed, uh, what happened is that we, uh, decided to intervene with the, uh, cystoscopy which, uh, confirmed the presence of the valve, as you can see, uh, and it's quite fascinating, um, referring That what the Torpedo said before, we see from the different perspective. We as a neurologist postnatally come from outside retrograde while the cystoscopy in the fetus uh comes anterograde. So this is a very important and interesting part of the story. Uh, which I'd like to develop even further. Of course, once we have confirmed the diagnosis, what we do proceed is to the resection of the valve, and, uh, the way in which we do resect in, uh, my center is by using a knife and by cutting through the valves. And, uh, we know that in other center and perhaps what it already has explained, you may have used electrocautery, which is a different technique which also mean to um undo the valves. And uh once we have done the resection, I'm gonna spare you the rest. What is the protocol? So once a patient got resected, and I'm, I'm quite happy to have heard from the tour um already what he said. It's a long journey. We always say to the family, the surgery is not the end of the story. It's actually the beginning of the journey, which is a long, long journey. So what happened in our center, we do, uh, observe the baby, we do, uh, have an early assessment of the bladder, and then we discharge and ideally, we plan another coming back to theater about 3 or 4 months later for checking the, the, the valve if any residual is left to then perform a urodynamic. At this point, why urodynamic? Urodynamic, and again, I'm, I'm, I'm happy to, to tale with the, uh, with Professor Reddy which said that the bladder function is very important. And at this phase, we can spot presence of high pressure, presence of detrusor activity, presence of very high bladder neck which might not even release, and that therefore, despite the bladder as the, the valves has been resected, bladder might still be obstructed by dysfunctional hypertrophic bladder neck. Then the patient received another appointment in clinic following a DMSA scan which informs us about the function of the kidneys. And uh at that point, comes to our valve clinic. And at that point, we might just do other assessment including the, the bladder, the uh blood test and ultrasound, and from there, we do have yearly checkup that lead us to our first initial full checkup that we normally schedule for around 5 years of age where we do restart all the investigation including DMSA scan, IXOGFR, and bladder assessment. And following that, the patient have yearly or two-yearly uh check up, up to the 10 and 15 years when again at the protocol, we do the full checkup. Uh, here in the UK we call the MOT which is what you do for your car as a full check before you have to go on the road. And then around 1617 years of age, they are ready to be transitioned to the other services. By telling the story like this, it seems that it's quite a simple and straightforward story. Well, the reality is a little bit different and the reality is that at every single point, something can go wrong or something can be not as straightforward. And I can just show you a few questions as an example. We said before that even the embryology and the nomenclature is not really uh a uniOC and there are questions and theories. Uh, we heard about antenatal intervention today in extent, but the question is, do we need to do it? Do we need to do it to all, to some? When? What? There could be many questions that uh still have, uh, to find a real answer. We mentioned about the primary reaction. Will it be cold knife? Will it be electrocautery the best choice? Uh, is antibiotic recommended? Can it be done? How long needs the, the child to be on antibiotic? And already mentioned the circumcision which of course in some center in some uh countries commonly used. And we also recommend for reducing the chance of infection, but is it the correct? Um, and then, of course, bladder again. Bladder investigation is such important and, and many times we have, uh, horrible bladder, as you can see now in, in this case. And the question is when should be better investigating the bladder? How would it be invasive? Would it be a non-invasive approach? How often should the bladder be looked at? And should we want to intervene, when shall we intervene and how? Can we do a CIC? Can we intervene with drugs, diversion, as Doctor Red said, sometimes it's not really well because we need to maintain the cycling bladder, and this in the later stage also will represent an issue. I can carry on a long and long and long because there are so many points where we could have questioned and we could have discussion about that. Something that can help us is looking at what is published. And in the most recent year, there is a grow body of uh uh publication for what regards valve. And, and you can see that publication come from many centers, of course, uh Cincinnati and the Turan in particular are quite a, a good example of uh uh publication. But by looking analytically to all the publication related to posterior valve, we can find many case reports, we can find a small series, or we can find the large series but of patients recruited over decades. And this cannot be correct because in decades, the situation change. There are a lot of advancement in the treatment, a lot of change in the patient. And if we look at what is the level of evidence, when we have something that uh has to be proved scientifically, we might focus on what are the core studies. And by definition, the core studies required a large number of patients over a long period. And if we want to be even more scientific and more um uh accurate, the randomized control trials are to be considered and these even more are critical in terms of number. And just to give you an example, so recent publication suggests that the incidents of valves are 1 in 3, 7000. And if you follow the European Commission on Public Health, who define that a rare disease is whenever it's affected 1, less than 1 in 2000, or if you follow the US Rare Disease Act, it's talking about 1500. So we do talk about a rare condition. So how can we make an effort and what Doctor Reddy said is the collaboration with the multi-center. And I'm aware about multi-center collaboration which are already uh in a, in place. The Puma is one, of course, uh, in, in the US we have in Europe something similar. But I want to think big. And when you think big, I'm thinking why not think even bigger. So what I'm actually thinking of is something that is a truly international POE study group. And when I mean truly international, I mean global. And as Doctor Reddy said, we need to put the effort together. So what I have done, I have organized what I think is gonna be, uh, hopefully, a breakthrough of gathering people from all around the world. There is a virtual event which uh is scheduled for the end of this year, November 26 and 27, when we have a panel of experts coming from pretty much all around the world. Five continents will be represented from US, Canada, Brazil, South Africa, India. Turkey, Europe, all together we'll be discussing about valves from the antenatal to the post-natal and long-term plan. Ideally, this event will aim to create a truly global expert group with the idea to compare our approach, the strategies, looking at project and collaboration that uh uh will be possible together. Ideally, we would like to create an international registry and of course, also supporting what are the low-income countries which might have not access to all the facilities and expertise that we can offer to our patients. So I hope that uh this will be uh of interest and I will wait for you to join us. Thank you so much for again the opportunity.