Hi, everyone. Today our guest is Dr. Jose Perea, a pediatric surgeon at Cincinnati Children's, which has the nation's highest volume photoscopic center. Dr. Perea also specializes in neonatal and fetal malformations, and he is the endoscopic fetal surgery director in Cincinnati Children's Fetal Care Center. There are a few conditions in fetal surgery that we can completely fix and target the cause of the problem, but in most of the cases, we are only able to improve the patient's condition.
And fortunately, we have very good tools for prenatal diagnosis and management. In one of our previous episodes, we talked about in utero diagnosis and surgical management techniques, including open fetal surgery and exit procedure. And this time we'll talk about minimally invasive fetal surgery or fetoscopy. Let's hear from Dr. Perea. Fetoscopy is the most important technique that we are using and probably the most promising for the future.
So we are using small instruments and we are treating different conditions. For instance, when there is a different problem in the monocoreal twins sharing one placenta, we can use this instrument. We'll talk a little bit about twin to twin transfusion syndrome or TTTs. Usually twins have connections in the same placenta that interchange blood. The issue arises when one twin transfers more blood to the other rather than it being a balanced exchange.
If one baby is given more, what happens is the donor starts to be dehydrated and stops to pee. So the initial outcome is a reduction in amniotic fluid as it consists of fetal urine. And the other baby is having a lot of volume, so it's hyperhydrated and it's urinating a lot. Both babies are at risk of life. So this is the first step to diagnose the problem. There are five stages of TTTs. Let's review them with Dr. Perea.
We established that more than eight and less than two are the limits of normality and this established stage one. Here we talk about the imbalance of amniotic fluid with a small amount, which is less than two centimeters around the donor twin and a large amount, which is more than eight centimeters around the recipient twin. In this stage, the twins are often more than 20 percent different in size. When there is no bladder in the donor, we say stage two.
Like Dr. Perea mentioned, it is considered stage two when the bladder of the donor twin is not visible or it does not fill with urine during an ultrasound exam. When the dopers are abnormal because one of the babies is sick of both, we say stage three. In stage three, the imbalance of blood flow starts to affect the heart function in one or both babies. This is seen in abnormal blood flow in the umbilical cords or hearts of the twins. When one baby is very sick and hydropic, stage four.
In this stage, the imbalance of blood flow causes signs of heart failure in one of the twins. And in stage five, which is the most serious one, one or both of the twins has passed away from severe TTTs. What do we do? So just to stop the transfusion, we go with the scope and we see the surface of the placenta and then we follow every single vessel going one way to the other and we do a mapping. And after that, we can photocoagulate these connections. For photocoagulation, they use YAG laser.
In simple terms, a YAG laser works by sending intense focused beams of light to specific areas of the body. This can be used to cut, remove or shape tissue in a very controlled way, causing minimal damage to the surrounding areas. Common use cases in medicine are cataract surgery, skin treatments, removal of kidney stones, and in our case, photoscopy. We did more than 2000 evaluations in our center and we did more than 1200 procedures with laser for twins.
So probably one of the biggest series worldwide with pretty good results. During the first three stages, the survival rate for at least one twin is 92% and the survival rate for both twins is 75% and at the fourth stage, they had a decent chance of survival being 91% for at least one twin and 70% for both. The goal is to have these babies going home, even one is bigger than the other. Photoscopy is also useful to release amniotic bends.
Amniotic bend syndrome, also known as constriction ring syndrome, happens when fibrous bends of the amniotic sac get tangled around the developing fetus, mostly in extremities, and in the rare cases, the bends wrap around the fetus' head or umbilical cord. So we did a good model in the fetal limb again when I was in Barcelona. We were trying to do it photoscopically so with the laser we can cut and release the constriction point. We transferred this to the human many years ago.
And Cincinnati Children's, they did more than 50 evaluations and 25 surgeries. And most of the cases are done around 23 weeks of gestation. They use just lasers or a combination of laser and micro-instruments. Our survival rate is 94% with good results. And finally, we can put the scope in the bladder. Sometimes we have obstructions of the bladder, mostly posterior retinal valves that generate low urinary tract obstructions and big bladder.
Basically in the MRI, you'll see a huge bladder in the fetus and fetal surgeons are able to access inside. A basic amniotic shunt can be a good bypass for this urine, but these devices usually migrate and dislodge and sometimes needs two or three. One of the best things to do is just to put the scope and see so we can have a diagnosis of a retinal valve from the belly or just retral atresia. With this technique, fetal surgeons can try to use a laser just to open the valves.
This ablation can be done with the laser when we have good angle. But if not, we can still place a transuretor catheter or combination of both just to have a good voiding of the bladder and potentially save the lives of these babies having amniotic fluid around. And the last use case of the topical we'll talk about in our podcast today is congenital diaphragmatic hernia or CDH. Congenital diaphragmatic hernia is a great topic for a fetus.
As you know, CDH produce a hole in one or two of the diaphragms and allow the bowel and all the organs, mostly the liver, to go up to the chest and compress the normal lung. And this leads to the cessation of normal lung development. These babies have severe problems to breathe and to ventilate and oxygenate epineutically.
So even in the best hospital in the world with the best neonatology and the best instruments, including high frequency and ECMO, some babies still not make it because the severe pulmonary hypoplexia. The sole intervention available to address these situations involves promoting lung growth within the womb at a stage when the fetus does not yet require their lungs for breathing. So how can this be accomplished?
We know that just blocking the trachea so we can maintain the fluid that the lungs are producing like a gland. And this lung fluid is essential for lung growth. Dr. Pere and his team created a model of tracheal occlusion in fetal lamps and analyzed the intrapulmonary fluid and did a proteomic profile. Results are very interesting. Huge number of proteins and growth factors involved in lung development.
But the molecules, the proteins that are enhancing the induction of cell proliferation are the most important using the NKT in this process and the BNT signaling. Dr. Pere says all this is basic science. If you ask how they select the patients, how they can offer tracheal occlusion and categorize the severity of this hernias, the answer is prenatal ultrasounds and fetal MRI.
So with the ultrasound, we can do the tracing and calculate the area is the most reliable, more than the diameters and calculate the lung hair ratio or most likely the observed to expect lung hair ratio. Then we have a long to head ratio of 25% or less from what is expected in a normal baby. That means we have severe or extremely severe cases with a very, very low survival. Okay, let's say we have a fetus eligible for the treatment. So what is the technique of tracheal occlusion?
We introduce the fetus scope in the mouth, go into the glottis inside the trachea and deploy a balloon that is detachable. Balloon is seven millimeters diameter. It's only one company producing these balloons so far. We can understand it's very difficult to go through the mouth of a baby in utero. So for tracheal occlusion, fetal position is very critical.
So at some point, if the position is not favorable, we need to spend time just for doing fetal version until we get a good position to achieve that trachea access. All right, the fetus is at a good position. We are inside the trachea, we push the balloon and inflate it from outside. What's next? Once the balloon is completely inflated, including the lumen of the trachea, then we can pull the balloon, push back the catheter and lift balloon for six to eight weeks for tracheal occlusion.
The previous experience in Europe in more than 200 cases was significant improvement in this severe category. Survival going from 8% to 55%. Here at Cincinnati Children's, including the ECMO, survival rates went from 40% to 85%. Main goal is to improve the patient's condition with less pulmonary hypertension and be able to send them home earlier. The goal is just to obtain a baby with not normal lungs. That's impossible, but at least better lungs.
Just to avoid high frequency, just to avoid ECMO, just to avoid significant pulmonary hypertension. And lastly, Dr. Pera would like to talk about his stake on the future of fetal surgery. We need to enhance innovation and include other anomalies. So we are working in the possibility to include repair of severe cleft lip palates or hydrocephalus.
Obviously, we will need to extend the fetoscopic approach, use new technologies, and for sure stem cell therapy and tissue engineer will be very important in the future. Hopefully with international collaboration that I like to share all my ideas and collaborate with other centers and progress in the field.
In summary, the task could be emerges as a groundbreaking, minimally invasive approach in fetal surgery, offering substantial hope for treating conditions such as twin to twin transfusion syndrome, amniotic band syndrome, and congenital diaphragmatic hernia.
This innovative technique enhances the survival prospects for twins affected by TTTS, facilitates the removal of amniotic bands to avoid potential amputations or fetal loss, and enables tracheal occlusion to stimulate in utero lung development in fetuses diagnosed with CDH. Dr. Pera further highlights the bright future of fetal surgery and emphasizes the advent of cutting edge advancements such as stem cell therapy and the power of global collaboration.