1 00:00:00,000 --> 00:00:13,080 Hi, everyone. 2 00:00:13,080 --> 00:00:18,680 Today our guest is Dr. Jose Perea, a pediatric surgeon at Cincinnati Children's, which has 3 00:00:18,680 --> 00:00:21,680 the nation's highest volume photoscopic center. 4 00:00:21,680 --> 00:00:27,600 Dr. Perea also specializes in neonatal and fetal malformations, and he is the endoscopic 5 00:00:27,600 --> 00:00:33,400 fetal surgery director in Cincinnati Children's Fetal Care Center. 6 00:00:33,400 --> 00:00:38,360 There are a few conditions in fetal surgery that we can completely fix and target the 7 00:00:38,360 --> 00:00:43,880 cause of the problem, but in most of the cases, we are only able to improve the patient's 8 00:00:43,880 --> 00:00:44,880 condition. 9 00:00:44,880 --> 00:00:50,480 And fortunately, we have very good tools for prenatal diagnosis and management. 10 00:00:50,480 --> 00:00:55,760 In one of our previous episodes, we talked about in utero diagnosis and surgical management 11 00:00:55,760 --> 00:00:59,600 techniques, including open fetal surgery and exit procedure. 12 00:00:59,600 --> 00:01:04,440 And this time we'll talk about minimally invasive fetal surgery or fetoscopy. 13 00:01:04,440 --> 00:01:05,440 Let's hear from Dr. Perea. 14 00:01:05,440 --> 00:01:11,040 Fetoscopy is the most important technique that we are using and probably the most promising 15 00:01:11,040 --> 00:01:12,040 for the future. 16 00:01:12,040 --> 00:01:15,920 So we are using small instruments and we are treating different conditions. 17 00:01:15,920 --> 00:01:21,200 For instance, when there is a different problem in the monocoreal twins sharing one placenta, 18 00:01:21,200 --> 00:01:22,560 we can use this instrument. 19 00:01:22,560 --> 00:01:27,760 We'll talk a little bit about twin to twin transfusion syndrome or TTTs. 20 00:01:27,760 --> 00:01:32,240 Usually twins have connections in the same placenta that interchange blood. 21 00:01:32,240 --> 00:01:36,720 The issue arises when one twin transfers more blood to the other rather than it being a 22 00:01:36,720 --> 00:01:37,720 balanced exchange. 23 00:01:37,720 --> 00:01:44,240 If one baby is given more, what happens is the donor starts to be dehydrated and stops 24 00:01:44,240 --> 00:01:45,240 to pee. 25 00:01:45,240 --> 00:01:50,160 So the initial outcome is a reduction in amniotic fluid as it consists of fetal urine. 26 00:01:50,160 --> 00:01:54,240 And the other baby is having a lot of volume, so it's hyperhydrated and it's urinating 27 00:01:54,240 --> 00:01:55,240 a lot. 28 00:01:55,240 --> 00:01:56,680 Both babies are at risk of life. 29 00:01:56,680 --> 00:01:59,920 So this is the first step to diagnose the problem. 30 00:01:59,920 --> 00:02:02,320 There are five stages of TTTs. 31 00:02:02,320 --> 00:02:03,880 Let's review them with Dr. Perea. 32 00:02:03,880 --> 00:02:08,640 We established that more than eight and less than two are the limits of normality and this 33 00:02:08,640 --> 00:02:10,560 established stage one. 34 00:02:10,560 --> 00:02:15,040 Here we talk about the imbalance of amniotic fluid with a small amount, which is less than 35 00:02:15,040 --> 00:02:19,520 two centimeters around the donor twin and a large amount, which is more than eight centimeters 36 00:02:19,520 --> 00:02:20,980 around the recipient twin. 37 00:02:20,980 --> 00:02:25,960 In this stage, the twins are often more than 20 percent different in size. 38 00:02:25,960 --> 00:02:29,760 When there is no bladder in the donor, we say stage two. 39 00:02:29,760 --> 00:02:34,080 Like Dr. Perea mentioned, it is considered stage two when the bladder of the donor twin 40 00:02:34,080 --> 00:02:38,940 is not visible or it does not fill with urine during an ultrasound exam. 41 00:02:38,940 --> 00:02:44,140 When the dopers are abnormal because one of the babies is sick of both, we say stage three. 42 00:02:44,140 --> 00:02:48,560 In stage three, the imbalance of blood flow starts to affect the heart function in one 43 00:02:48,560 --> 00:02:49,740 or both babies. 44 00:02:49,740 --> 00:02:54,120 This is seen in abnormal blood flow in the umbilical cords or hearts of the twins. 45 00:02:54,120 --> 00:02:56,920 When one baby is very sick and hydropic, stage four. 46 00:02:56,920 --> 00:03:00,920 In this stage, the imbalance of blood flow causes signs of heart failure in one of the 47 00:03:00,920 --> 00:03:01,920 twins. 48 00:03:01,920 --> 00:03:06,520 And in stage five, which is the most serious one, one or both of the twins has passed away 49 00:03:06,520 --> 00:03:07,520 from severe TTTs. 50 00:03:07,520 --> 00:03:09,060 What do we do? 51 00:03:09,060 --> 00:03:13,600 So just to stop the transfusion, we go with the scope and we see the surface of the placenta 52 00:03:13,600 --> 00:03:18,760 and then we follow every single vessel going one way to the other and we do a mapping. 53 00:03:18,760 --> 00:03:22,360 And after that, we can photocoagulate these connections. 54 00:03:22,360 --> 00:03:25,400 For photocoagulation, they use YAG laser. 55 00:03:25,400 --> 00:03:30,360 In simple terms, a YAG laser works by sending intense focused beams of light to specific 56 00:03:30,360 --> 00:03:32,000 areas of the body. 57 00:03:32,000 --> 00:03:36,680 This can be used to cut, remove or shape tissue in a very controlled way, causing minimal 58 00:03:36,680 --> 00:03:39,100 damage to the surrounding areas. 59 00:03:39,100 --> 00:03:43,640 Common use cases in medicine are cataract surgery, skin treatments, removal of kidney 60 00:03:43,640 --> 00:03:46,080 stones, and in our case, photoscopy. 61 00:03:46,080 --> 00:03:52,320 We did more than 2000 evaluations in our center and we did more than 1200 procedures with 62 00:03:52,320 --> 00:03:53,800 laser for twins. 63 00:03:53,800 --> 00:03:57,760 So probably one of the biggest series worldwide with pretty good results. 64 00:03:57,760 --> 00:04:03,240 During the first three stages, the survival rate for at least one twin is 92% and the 65 00:04:03,240 --> 00:04:09,280 survival rate for both twins is 75% and at the fourth stage, they had a decent chance 66 00:04:09,280 --> 00:04:14,000 of survival being 91% for at least one twin and 70% for both. 67 00:04:14,000 --> 00:04:18,200 The goal is to have these babies going home, even one is bigger than the other. 68 00:04:18,200 --> 00:04:21,460 Photoscopy is also useful to release amniotic bends. 69 00:04:21,460 --> 00:04:26,280 Amniotic bend syndrome, also known as constriction ring syndrome, happens when fibrous bends 70 00:04:26,280 --> 00:04:31,120 of the amniotic sac get tangled around the developing fetus, mostly in extremities, and 71 00:04:31,120 --> 00:04:35,700 in the rare cases, the bends wrap around the fetus' head or umbilical cord. 72 00:04:35,700 --> 00:04:39,240 So we did a good model in the fetal limb again when I was in Barcelona. 73 00:04:39,240 --> 00:04:44,560 We were trying to do it photoscopically so with the laser we can cut and release the 74 00:04:44,560 --> 00:04:46,120 constriction point. 75 00:04:46,120 --> 00:04:49,240 We transferred this to the human many years ago. 76 00:04:49,240 --> 00:04:54,320 And Cincinnati Children's, they did more than 50 evaluations and 25 surgeries. 77 00:04:54,320 --> 00:04:57,760 And most of the cases are done around 23 weeks of gestation. 78 00:04:57,760 --> 00:05:02,040 They use just lasers or a combination of laser and micro-instruments. 79 00:05:02,040 --> 00:05:05,320 Our survival rate is 94% with good results. 80 00:05:05,320 --> 00:05:08,560 And finally, we can put the scope in the bladder. 81 00:05:08,560 --> 00:05:13,720 Sometimes we have obstructions of the bladder, mostly posterior retinal valves that generate 82 00:05:13,720 --> 00:05:17,600 low urinary tract obstructions and big bladder. 83 00:05:17,600 --> 00:05:21,320 Basically in the MRI, you'll see a huge bladder in the fetus and fetal surgeons are able to 84 00:05:21,320 --> 00:05:22,320 access inside. 85 00:05:22,320 --> 00:05:27,020 A basic amniotic shunt can be a good bypass for this urine, but these devices usually 86 00:05:27,020 --> 00:05:30,200 migrate and dislodge and sometimes needs two or three. 87 00:05:30,200 --> 00:05:34,520 One of the best things to do is just to put the scope and see so we can have a diagnosis 88 00:05:34,520 --> 00:05:37,960 of a retinal valve from the belly or just retral atresia. 89 00:05:37,960 --> 00:05:42,600 With this technique, fetal surgeons can try to use a laser just to open the valves. 90 00:05:42,600 --> 00:05:46,240 This ablation can be done with the laser when we have good angle. 91 00:05:46,240 --> 00:05:51,880 But if not, we can still place a transuretor catheter or combination of both just to have 92 00:05:51,880 --> 00:05:56,520 a good voiding of the bladder and potentially save the lives of these babies having amniotic 93 00:05:56,520 --> 00:05:57,520 fluid around. 94 00:05:57,520 --> 00:06:01,520 And the last use case of the topical we'll talk about in our podcast today is congenital 95 00:06:01,520 --> 00:06:04,400 diaphragmatic hernia or CDH. 96 00:06:04,400 --> 00:06:08,720 Congenital diaphragmatic hernia is a great topic for a fetus. 97 00:06:08,720 --> 00:06:14,800 As you know, CDH produce a hole in one or two of the diaphragms and allow the bowel 98 00:06:14,800 --> 00:06:20,300 and all the organs, mostly the liver, to go up to the chest and compress the normal lung. 99 00:06:20,300 --> 00:06:23,480 And this leads to the cessation of normal lung development. 100 00:06:23,480 --> 00:06:29,060 These babies have severe problems to breathe and to ventilate and oxygenate epineutically. 101 00:06:29,060 --> 00:06:32,960 So even in the best hospital in the world with the best neonatology and the best instruments, 102 00:06:32,960 --> 00:06:38,040 including high frequency and ECMO, some babies still not make it because the severe pulmonary 103 00:06:38,040 --> 00:06:39,040 hypoplexia. 104 00:06:39,040 --> 00:06:44,280 The sole intervention available to address these situations involves promoting lung growth 105 00:06:44,280 --> 00:06:49,240 within the womb at a stage when the fetus does not yet require their lungs for breathing. 106 00:06:49,240 --> 00:06:51,420 So how can this be accomplished? 107 00:06:51,420 --> 00:06:56,760 We know that just blocking the trachea so we can maintain the fluid that the lungs are 108 00:06:56,760 --> 00:06:58,200 producing like a gland. 109 00:06:58,200 --> 00:07:01,600 And this lung fluid is essential for lung growth. 110 00:07:01,600 --> 00:07:06,680 Dr. Pere and his team created a model of tracheal occlusion in fetal lamps and analyzed the 111 00:07:06,680 --> 00:07:10,040 intrapulmonary fluid and did a proteomic profile. 112 00:07:10,040 --> 00:07:11,480 Results are very interesting. 113 00:07:11,480 --> 00:07:16,140 Huge number of proteins and growth factors involved in lung development. 114 00:07:16,140 --> 00:07:20,820 But the molecules, the proteins that are enhancing the induction of cell proliferation are the 115 00:07:20,820 --> 00:07:26,040 most important using the NKT in this process and the BNT signaling. 116 00:07:26,040 --> 00:07:28,920 Dr. Pere says all this is basic science. 117 00:07:28,920 --> 00:07:33,040 If you ask how they select the patients, how they can offer tracheal occlusion and categorize 118 00:07:33,040 --> 00:07:38,080 the severity of this hernias, the answer is prenatal ultrasounds and fetal MRI. 119 00:07:38,080 --> 00:07:43,280 So with the ultrasound, we can do the tracing and calculate the area is the most reliable, 120 00:07:43,280 --> 00:07:48,760 more than the diameters and calculate the lung hair ratio or most likely the observed 121 00:07:48,760 --> 00:07:50,040 to expect lung hair ratio. 122 00:07:50,040 --> 00:07:55,760 Then we have a long to head ratio of 25% or less from what is expected in a normal baby. 123 00:07:55,760 --> 00:08:00,600 That means we have severe or extremely severe cases with a very, very low survival. 124 00:08:00,600 --> 00:08:04,760 Okay, let's say we have a fetus eligible for the treatment. 125 00:08:04,760 --> 00:08:07,480 So what is the technique of tracheal occlusion? 126 00:08:07,480 --> 00:08:11,560 We introduce the fetus scope in the mouth, go into the glottis inside the trachea and 127 00:08:11,560 --> 00:08:14,200 deploy a balloon that is detachable. 128 00:08:14,200 --> 00:08:16,600 Balloon is seven millimeters diameter. 129 00:08:16,600 --> 00:08:19,240 It's only one company producing these balloons so far. 130 00:08:19,240 --> 00:08:23,160 We can understand it's very difficult to go through the mouth of a baby in utero. 131 00:08:23,160 --> 00:08:26,720 So for tracheal occlusion, fetal position is very critical. 132 00:08:26,720 --> 00:08:31,360 So at some point, if the position is not favorable, we need to spend time just for doing fetal 133 00:08:31,360 --> 00:08:36,080 version until we get a good position to achieve that trachea access. 134 00:08:36,080 --> 00:08:38,600 All right, the fetus is at a good position. 135 00:08:38,600 --> 00:08:43,440 We are inside the trachea, we push the balloon and inflate it from outside. 136 00:08:43,440 --> 00:08:44,440 What's next? 137 00:08:44,440 --> 00:08:49,200 Once the balloon is completely inflated, including the lumen of the trachea, then we can pull 138 00:08:49,200 --> 00:08:54,720 the balloon, push back the catheter and lift balloon for six to eight weeks for tracheal 139 00:08:54,720 --> 00:08:55,720 occlusion. 140 00:08:55,720 --> 00:09:00,360 The previous experience in Europe in more than 200 cases was significant improvement 141 00:09:00,360 --> 00:09:02,000 in this severe category. 142 00:09:02,000 --> 00:09:04,880 Survival going from 8% to 55%. 143 00:09:04,880 --> 00:09:11,040 Here at Cincinnati Children's, including the ECMO, survival rates went from 40% to 85%. 144 00:09:11,040 --> 00:09:16,280 Main goal is to improve the patient's condition with less pulmonary hypertension and be able 145 00:09:16,280 --> 00:09:17,960 to send them home earlier. 146 00:09:17,960 --> 00:09:23,440 The goal is just to obtain a baby with not normal lungs. 147 00:09:23,440 --> 00:09:25,800 That's impossible, but at least better lungs. 148 00:09:25,800 --> 00:09:30,360 Just to avoid high frequency, just to avoid ECMO, just to avoid significant pulmonary 149 00:09:30,360 --> 00:09:31,360 hypertension. 150 00:09:31,360 --> 00:09:35,520 And lastly, Dr. Pera would like to talk about his stake on the future of fetal surgery. 151 00:09:35,520 --> 00:09:38,440 We need to enhance innovation and include other anomalies. 152 00:09:38,440 --> 00:09:44,920 So we are working in the possibility to include repair of severe cleft lip palates or hydrocephalus. 153 00:09:44,920 --> 00:09:50,280 Obviously, we will need to extend the fetoscopic approach, use new technologies, and for sure 154 00:09:50,280 --> 00:09:55,520 stem cell therapy and tissue engineer will be very important in the future. 155 00:09:55,520 --> 00:10:00,240 Hopefully with international collaboration that I like to share all my ideas and collaborate 156 00:10:00,240 --> 00:10:03,480 with other centers and progress in the field. 157 00:10:03,480 --> 00:10:07,400 In summary, the task could be emerges as a groundbreaking, minimally invasive approach 158 00:10:07,400 --> 00:10:12,280 in fetal surgery, offering substantial hope for treating conditions such as twin to twin 159 00:10:12,280 --> 00:10:17,840 transfusion syndrome, amniotic band syndrome, and congenital diaphragmatic hernia. 160 00:10:17,840 --> 00:10:23,520 This innovative technique enhances the survival prospects for twins affected by TTTS, facilitates 161 00:10:23,520 --> 00:10:29,260 the removal of amniotic bands to avoid potential amputations or fetal loss, and enables tracheal 162 00:10:29,260 --> 00:10:34,040 occlusion to stimulate in utero lung development in fetuses diagnosed with CDH. 163 00:10:34,040 --> 00:10:38,840 Dr. Pera further highlights the bright future of fetal surgery and emphasizes the advent 164 00:10:38,840 --> 00:10:44,080 of cutting edge advancements such as stem cell therapy and the power of global collaboration.