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N. Scott Adzick: This is Dr. Scott Adzick from the Center for Fetal Diagnosis and Treatment at the Children's Hospital of Philadelphia.
I'm going to give an update on fetal lung lesions.
This shows our referral diagnoses to the Center for Fetal Diagnosis and Treatment over the past 16 years. And note there have been more than 1,000 fetal lung lesion referrals during that time period.
Here's the prenatal differential diagnosis of a chest lesion. I'm going to focus on the left hand side on lung lesions, including congenital cystic adenomatoid malformation, or CCAM for short, bronchopulmonary sequestration, either intralobar or extralobar, or BPS for short, hybrid lesions, which are a combination of the two, and mention bronchial stenosis and atresia. I will not cover in detail congenital diaphragmatic hernia, that'll be the topic of another CME lecture for the Center for Fetal Diagnosis and Treatment, nor will I cover duplication cysts, thymic masses, teratomas, and so forth.
The differential diagnosis of a fetal lung mass includes CCAMs, which can be either macrocystic or microcystic, bronchopulmonary sequestration, or hybrid lesions.
The sonographic predictors of outcome in CCAM, we characterized years ago as either microcystic, shown on the right side, in which very, very small cysts are present and cytologically usually a Stocker classification III, or larger cystic lesions, macrocystic, which are usually Stocker type I.
The prenatal diagnosis for a congenital cystic adenomatoid malformation are primarily by ultrasound, can categorize the lesions in those two cystic types. We found a fetal MRI to be extremely useful to help determine which lobe is affected and it differentiates CCAM from BPS or hybrid lesions. And we use fetal MRI routinely and helped develop this technology about 15 years ago. As far as prognosis though, the growth and overall size of the lesion is more important than the sonographic appearance by cyst type or the Stocker classification.
Here on the left is a CCAM viewed by fetal MRI, straightforward to see, affects one lobe, in this case the left lower lobe. And a bronchopulmonary sequestration on the right side, a solid lesion that has a systemic arterial feeding vessel, which is the dark stripe feeding the lesion.
Dr. Alan Flake and his laboratory of colleagues have shown that FGF10 overexpression induces the full spectrum of congenital cystic adenomatoid malformation. In a fetal rat model, he showed that fiberblast growth factor-10, which is a mesenchymal growth factor, regulates epithelial and mesenchymal interactions during the lung branching morphogenesis, and showed that transuterine ultrasound-guided intraparenchymal microinjections of an adenoviral vector encoding the FGF10 transgene in the fetal lung results in the FGF10 overexpression during various stages of lung growth depending on when the injection is done. So a central injection early in gestation leads on the far right to a macrocystic lesion. And conversely, a late gestation injection peripherally leads to a microcystic lesion.
And this just shows in summary again how FGF10 overexpression induces the full spectrum of CCAM from macrocystic lesions on the left all the way through to microcystic lesions.
And again it depends on embryologic timing of the insult and where in the lung and the injection has occurred. So this is a beautiful model, which may help us in the future craft biological therapeutic strategies to treat CCAM when it's very large before birth.
There's a broad spectrum of clinical severity for fetal lung lesions. A fetal lung mass may compress, if it's large, the esophagus, leading to polyhydramnios due to compression of the esophagus by the lesion and decrease fetal swallowing of amniotic fluid. The CCAM can compress the normal lung tissue leading to relative pulmonary hypoplasia. And in the more--and in the most severe cases, a large lesion can compress the heart and the vena cava and the lymphatics, leading to hydrops or fetal cardiovascular failure, fetal right heart failure before birth. Most lesions, however, do not have these pathophysiologic consequences before birth and can simply be followed and treated after birth.
Beverly Coleman and Tim Crombleholme about 14 years ago came up with a way to measure size of CCAMs before birth, the CCAM mass volume to head circumference ratio or CVR for short. They use the formula for a prolate ellipse, which is shown on this slide, to measure the lesion volume or size and correct for gestational age or fetal size by dividing this by the fetal head circumference, hence, CCAM volume ratio or CVR for short. In a prospective evaluation of 58 patients, these investigators at CHOP showed that a CVR greater than 1.6 put the fetus at high risk to develop fetal hydrops. In those lesions not developing hydrops, or not causing hydrops, we learned as well by following fetuses serially by sonographic observation that rapid growth is possible between 18 and 25 weeks gestation. There's usually a growth plateau at 25 to 28 weeks gestation and characteristically no growth of the lesion after the plateau except for large cystic lesions. And we learned as well that regression and size of the lesion late in gestation is pretty common.v
The CCAM mass volume to head circumference ratio, or CVR, is very important in counseling families in terms of what to expect, prepares the team in case fetal therapy might be needed at some point, and also targets how frequent sonographic surveillance should occur. For a high-risk fetus with a large lesion, a CCAM volume ratio greater than 1.6, that fetus is at risk for hydrops and warrants two to three times a week evaluations by sonography. For those with a lesion between 1.2 and 1.6, they can initially be screened twice a week and then weekly depending on the growth. And then for those less than 1.2 might be seen every two to three weeks depending on the growth with the goal to get out to the plateau time period at 25 to 28 weeks gestation.
One of the pathophysiologic consequences of a large fetal lung lesion is that the fetus with a CCAM who develops fetal hydrops can cause placentomegaly, a big, thick, edematous placenta, which in turn can make the mother sick, the so-called maternal mirror syndrome, which we--a term we came up with years ago. This is a severe preeclamptic state characterized by maternal hypertension, proteinuria, can lead to peripheral and pulmonary edema in which the maternal condition begins to mirror that of her sick fetus. This can be seen in other types of placentomegaly. It may be related to release of placental basal active factors. And unfortunately this in pathophysiologic state can be reversed only by delivery of the fetus and the placenta, and the sick, premature, hydropping newborn invariably dies. So it might make sense to go after or to treat fetuses with CCAM who develop fetal hydrops before the evolution to maternal mirror syndrome where the mother's health would be in jeopardy.
This sort of thinking 25 years ago required definition of the fetal disease, in this case, a CCAM by serial sonographic observation, and then going to the laboratory and working in fetal sheep and fetal monkeys to develop experimental models of a CCAM to look at the pathophysiologic principals and to see if fetal therapy, in this case, decompression of a lesion by a shot or a resection before birth, could lead to a good kid. And all this had to be done prior to applying it clinically.
When I was a research fellow 30 years ago at University of California, San Francisco, I did a series of experiments in fetal sheep involving lobectomies and pneumonectomies. And this shows a fetal lamb at 65 days gestation. You can see the left forelimb with a little hoof on it so you know it's a lamb. And this is at mid-gestation, of course, with fetal sheep. And a thoracotomy has been performed and you can see the fetal heart and fetal lung. So we developed the techniques to do lobectomies and pneumonectomies before birth.
After pneumonectomy, in this case, there's remarkable compensatory lung growth of the remaining lung, which is very encouraging. This compensatory lung growth is striking in its tempo.
The next step was to test the hypothesis that a large CCAM would lead to fetal cardiovascular compromise and internally to fetal heart failure, or hydrops manifested by ascites first and then the development of skin and scalp edema.
In our laboratory at that time, about 25 years ago, one of my research fellows, Henry Rice, did a chronically catheterized prep in sheep at mid-gestation. He placed various lines, central venous pressure, arterial catheter, amniotic catheter, and then an intrathoracic balloon catheter. And he gradually inflated the balloon to simulate a growing CCAM.
And showed that by monitoring central venous pressure on the Y-axis and tissue expander volume on the X-axis. As the growing tissue expander to simulate a growing CCAM enlarged, that eventually the CVP rose to the point where the fetus developed hydrops, ascites, skin and scalp edema. And then in my deflating the tissue expander to simulate resection before birth, those findings of fetal hydrops resolved.
And this shows a cast injection on the arterial side in blue, and on the venous side in white. And one can see right in the middle of the figure where the tissue expander was. There's a big mediastinal shift. The heart and vena cava are compressed. And one can also see the constellation pattern, the arborization of the vessels in the liver.
At this point in time, we figured that open fetal surgery was only justifiable for life-threatening malformations in which there was a poor prognosis without an intervention, we showed that this was efficacious in animal models as far as treatment was concerned, and to show that this could all be done at reasonably low maternal risk.
We developed techniques in fetal rhesus monkeys, about 400 fetal rhesus monkey preparations. The surgical, anesthetic, and tocolytic techniques were defined prior to clinical application. And since the maternal monkeys returned to the breeding colony, we showed that there was no impairment of future reproductive capacity by the fetal surgical intervention. And we showed that we could treat effectively preterm labor, although that is not a completely solved problem clinically of course.
And this led to techniques to treat life-threatening fetal malformations involving an operation on the mother and on the fetus, as shown here.
For a fetal CCAM resection, this involves maternal general anesthesia, a maternal laparotomy. And here in this slide, one can see the uterus in a sterile intraoperative ultrasound probe to determine the placental position and the fetal position.
This shows the hysterotomy using an absorbable stapling device that's been performed, you see the uterus, you see the fetal left arm, and a left thoracotomy is being performed. And in the middle portion of the figure, one can see a very large congenital cystic adenomatoid malformation that affects the left lower lobe.
And this lobe is being removed. You can see that this lesion filled adversely the entire fetal chest.
It's important, you can see after the removal of the lesion, one can see the residual left upper lobe, which will thereafter show remarkable compensatory lung growth, as well as the right lung will have the chance to grow because it's no longer squished.
And this shows the thoracotomy on the left side being closed. And again on the right side, full closure. And the fetus has an IV in and a pulse oximeter on, which is covered by foil.
The intraoperative management of these lesions is very important, involving the same maneuvers we use in treating and operating on a premature infant. Including pulse oximetry with a miniaturized probe that works on the tiny fetal hand at, say, 23 weeks gestation. Real-time fetal echocardiography provided by fetal cardiologists from our Fetal Heart Program that determine cardiac function, very important. And also intravenous access so that we can give blood or volume or medications.
Many lessons have been learned from the use of intraoperative fetal echocardiography in these and other open fetal surgery cases, such as those for spina bifida. And that we have seen findings such as aortic reversal of flow, ductal constriction, tricuspid regurgitation, and decrease in fetal heart rate, which require adjustments in terms of intraoperative management, whether it be fetal position, ruling out a compromised umbilical cord, making sure that uterine blood flow is good, and so forth.
This shows the maternal laparotomy closed. This is closed in layers with a subcuticular plastic surgical closure of the skin.
This shows a case, a recent case actually, 21 weeks gestation. The MRI findings are shown on the left with the CCAM volume ratio by ultrasound of 2.0. This fetus had developed skin and scalp edema as well as ascites. The mother was given two courses of steroids, which can stop the growth of the solid component of the lesion, but was unsuccessful in this case. And so by 23 weeks gestation, there's a fulminantly hydropping fetus, shown on the right side, with a CCAM volume ratio of 3.3 and also massive ascites. So this fetus underwent resection of the lesion.
And this shows an intraoperative video of that case. There's an entry in the placenta so a posterior frontal hysterotomy is performed. Stay sutures are placed. The cautery is used to incise down through the myometrium and through the membranes. Uterine stapling device is applied and it actually misfired so it was replaced again. The hysterotomy has been performed. The left hand is brought out for this left sided lesion. An IV is placed for blood products or for medications. A miniaturized pulse oximeter is placed and wrapped in foil to protect it from light so that it can work. This shows a very large fetal thoracotomy being performed. We've learned with these thoracotomies that one has to gradually deliver the lesion because it's like relief of cardiac tamponade, and it's a very large firm lesion. Take care of the vein, the brochus, and the artery. Closure of the chest in layers. And then closure of the uterus in layers. Once can see there's very good hemostasis. You can see the uterine stapling line there as well. Two layer closure and then we put in an omental patch and then close the laparotomy.
This shows that same case three and a half weeks post operatively, so now we're at 26 and a half weeks. There's already remarkable compensatory lung growth as shown on this MRI. You can see the two lungs and the fetal hydrops has resolved. This baby was delivered by ceasarean section at 35 weeks gestation. No positive pressure ventilation was required.
Years ago, after fetal CCAM resection associated with hydrops and lobectomy, we measured lung volumes by serial MRI before birth. And one can see tremendous compensatory lung growth not only on the affected side, but on the contralateral side because both sides' normal lung tissue was affected.
This shows the preoperative appearance at 23 weeks gestation, in this case, with a very large lesion. Fills the entire chest and causes ascites, signs of right heart failure, and skin and scalp edema. This lesion is removed by lobectomy. Six weeks post op on the right side. The mediastinum is back in the midline, the hydrops has resolved, and there's remarkable compensatory lung growth.
This shows the first patient at the Children's Hospital of Philadelphia who had a CCAM removed in 1996. He's now 16 years of age so we actually need a more recent photo of than these two.
This shows another patient who was treated before birth with his family.
Large macrocystic lesions as shown on this ultrasound--on the left side, sagittal view, on the right side, transverse view--can also be mischief makers before birth and cause fetal hydrops. This shows one such patient with a CCAM volume ratio of 1.45. This was followed and increased in size and fetal hydrops developed.
Our initial strategy is to simply do a fetal thoracentesis to drain the macrocyst. This may be therapeutic, although usually the lung fluid rapidly reaccumulates. It allows us to visualize how the cyst collapses and determine how much chronic drainage with a thoracoamniotic shunt will reduce the overall mass size. So you can do the preoperative, or pre tab, and post operative CVR measurements. It also helps to demonstrate any communication if there are multiple cysts present.
This shows the instruments for fetal shunt placement, which is all done percutaneously through the maternal abdomen with a local anesthesia. And a double pigtail catheter is placed, which is in the right lower corner of this slide.
This shows the technique for pleuroamniotic or thoracoamniotic shunt placement with a trocar placed into the cyst. And the one end of the double pigtail catheter placed into the cyst, the straight portion going for the chest wall. And the other end of the double pigtail catheter coming on the outside of the chest to keep it in place. This decompresses the cyst fluid into the amniotic fluid and removes the mass effect in the chest.
This shows a macrocystic CCAM by MRI at 24 weeks gestation with hydrops. Another huge lesion and massive ascites as well as skin and scalp edema, a CVR of 3.6. But after pleuroamniotic shunt placement, one can see that by ultrasound in the lower right hand corner, there's good decompression and the CVR has gone down to 0.8, which is certainly manageable.
This shows the appearance of one of these double pigtail catheters actually during an EXIT procedure, a fancy ceasarean section that I'll talk about in more detail. But in the middle of the slide you can see the outside portion of the double pigtail shunt, which can be simply removed at the time of birth.
One needs to watch for chest wall deformities secondary to shunt placement. This occurred in our series. In 77 percent of cases, there was some usually very subtle chest wall abnormality ranging from rib thinning to a slight concavity to, in two cases, fractures requiring thoracoplasty at the time of CCAM resection. These two cases, as shown here in one of the cases, severity correlated with the gestational age when the shunt was placed. These two cases were done in 18--in 20 weeks gestation. And I think the rapid decompression of the huge cyst affected chest wall growth.
This shows our experience with fetal CCAM in terms of therapy. Sixty-six cases where the indication for therapy is fetal hydrops. Fifteen or 26 with mostly solid lesions survived after resection at 21 to 31 weeks gestation and the average gestational age at delivery of the survivors was 33 weeks. And there's a very good quality of life for those survivors. Thirty to 40 fetuses with large cysts survived after placement of a thoracoamniotic shunt at an average gestational age at 23 weeks gestation, but the average gestational age at delivery of 34 weeks gestation.
Recently over the past few years, we've used maternal betamethasone therapy for CCAM, and this appears to be effective for the solid component of the lesion. We retrospectively reviewed patients with a CCAM or hybrid lesion treated with two maternal doses of steroids and looked at the growth rates and survival data compared to historical non-steroid treated controls.
And showed that betamethasone was ineffective for macrocystic lesions, but quite effective for microcystic lesions, even though those that have fetal hydrops. And this compares to a mortality of 100 percent and 56.2 percent, respectively, in historical non-treated controls. So we now use this on a routine basis for prenatally diagnosed solid lesions with a CVR greater than 1.4, even if hydrops is not developed.
The pathognomonic sign by sonography of a bronchopulmonary--bronchopulmonary sequestration is detection by a color flow Doppler of a systemic artery from the aorta to the fetal lung lesion. In prenatal ultrasonography, a BPS appears as a well defined echo dense homogeneous mass. The ability to differentiate intralobar and extralobar sequestration before birth is limited unless an extralobar sequestration is high leaded by a pleural effusion, or if it's located in the abdomen. So this shows a color flow Doppler ultrasound showing a large systemic arterial feeding vessel to a echo dense mass that is a bronchopulmonary sequestration.
These can be quite large. As shown in this slide, it fills up a good portion of the chest, very echo dense, easy to see.
These often disappear, so-called disappearing lesions, late in gestation. They're still there, but their echogenicity is the same, hence the surrounding normal lung.
And they may not be evident in chest x-ray--on chest x-ray after birth.
By CT scan, an extralobar sequestration without cysts is shown here in the diaphragmatic sulcus on the left side. We don't think there's a need to operate on small extralobar sequestrations without cysts. Those would be hybrid lesions if the cysts were present. We operate if the lesion is large or if it contains cysts or is causing high output cardiac failure due to a vascular steal through the lesion. If the sequestration is intralobar, we resect them after birth electively due to the infection risk.
In some bronchopulmonary sequestrations that are extralobar, they can cause fetal hydrops because of secretion of fluid into the pleural space under positive pressure causing a tension hydrothorax. This can be treated by a fetal thoracentesis or more effectively by a thoracoamniotic shunt.
We reviewed our experience with fetal sequestrations in 1998, 45 cases. Those without cysts that were so-called disappearing and documented by CT after birth to be quite small were not treated surgically. Those that required resection were those that were large or contained cysts or had caused fetal hydrops by tension hydrothorax before birth.
Bronchial atresia and its consequences are shown here. Main stem bronchial atresia is a very difficult problem to treat. It can lead to large lung expansion for the affected lung that can cause fetal hydrops and our clinical experience with this is quite limited. We currently have a baby in the Intensive Care Nursery who was treated with this--for this before birth. And if that baby survives it would be the first known survivor.
The EXIT procedure representing ex utero intrapartum therapy, or E-X-I-T, EXIT for short, is a way to treat fetuses with airway obstruction or fetuses with large lung lesions prior to the delivery late in gestation. This requires a multidisciplinary team, a pediatric surgeon, obstetrician, anesthesiologist, neonatologist, and nurses, deep general anesthesia for good uterine relaxation, supplemental fetal anesthesia by intramuscular vecuronium and fentanyl, sterile intraoperative sonography. The usual fetal surgical techniques with the hysterotomy performed with the uterine stapling device. And a variety of procedures can be performed and with reference to large CCAMs, including chest wall mass resections.
At CHOP we have experience with about 100 EXIT procedures. This includes 23 EXIT-to-resection of chest mass cases with survival in 21, for an overall survival rate of 91 percent. This is by far the largest experience in the world.
This shows a characteristic case. Diagnosis at 24 weeks gestation, macrocystic CCAM plus hydrops, CVR of 2.6. Progressing to at 27 weeks gestation, placement of a thoracoamniotic shunt with decompression, but there's still a large solid component to the CCAM. Late in gestation, CVR by ultrasound of 1.9 with persistent ascites and a solid mass effect, so an EXIT was performed.
This shows our experience with the EXIT in terms of the information summarizing those 23 cases. Average gestational age of the EXIT was 34 or 35.4 weeks. Mean CVR was 2.5 at presentation and 2.2 at the time of EXIT, so very large lesions late in gestation. Many of these fetuses had hydrops or polyhydramnios. The majority of them had been treated by a thoracentesis shunt, amnioreduction, and/or betamethasone. The average time of placental bypass for these 23 cases was 65 minutes. So in a very controlled circumstance you have time to do the resection and close the chest. Four of the 21 survivors still required the use of extracorporeal membrane oxygenation to treat pulmonary hypertension. Maternal complications included preterm labor in five cases due to polyhydramnios, chorioamnionitis in one case, and a blood transfusion to the mom in one case. Postoperative complications included an air leak requiring a reoperation, one chylothorax. There were two deaths in this series of 23 patients. One was a reoperation from bleeding and death in a 27 weeks gestation newborn where the EXIT was an act of desperation. And the other was a death due to pulmonary hyperplasia despite ECMO after prenatal shunt placement and the use of steroids.
This shows a video of an EXIT-to-CCAM resection. The hysterotomy has been made with the uterine stapling device, lower uterine segment intubation. We then secure the endotracheal tube to the upper gum with a stitch. Placement of an IV, pulse oximeter, fetal echocardiographic monitoring. Very large thoracotomy. In this case, through the fifth intercostal space because a very large lesion is present. There's the lesion. Thoracotomy is being made bigger. And then identification, isolation, ligation, and division, in this case, of the intrapulmonary vein. I mean, pulmonary arterial trunk to the lesion into the bronchus with suture ligation, as well for the vascular structures as shown here. And the lesion is removed. It's huge. Chest is then closed in layers. The lower half of the fetus is still inside the uterus to maintain the uterine volume. And once the baby is ventilated then the umbilical cord is ligated and divided and the baby is carried into the adjacent neonatal resuscitation room in the Special Delivery Unit.
So the EXIT successfully ensures uteroplacental gas exchange, fetal hemodynamic stability. There are expanding indications. We now have a very, very large clinical series of nearly 100 cases. The bottom line is that it converts a possible catastrophic emergency into a controlled, planned operation.
For those fetuses with large lesions who we think may not require the EXIT operation, it's a judgment call. And in many cases this can be a planned caesarean section with immediate resuscitation of the newborn and determination whether an immediate thoracotomy is required. And we're set up in the Special Delivery Unit with a caesarean section room, a neonatal resuscitation room, which is adjacent, and then adjacent to that is an additional operating room that can be used for the newborn resection.
So this shows the perinatal and postnatal management summary for lung lesions. For those in the far left, those prenatally diagnosed without a mediastinal shift and a small lesion, these will be asymptomatic, hence the majority of cases. They can deliver close to home. And then we do here at the Children's Hospital of Philadelphia a postnatal chest CT scan, actually a CTA, at about one to two months of age. And then do electroresection by either a muscle-sparing thoracotomy or by a thoracoscopy. For those fetuses with a mediastinal shift due to the lung lesion, but without major cardiac and/or lung compression, we predict these will likely be symptomatic. They should be delivered at a tertiary center such as CHOP and will require a postnatal resection either immediately after birth or at least during the neonatal admission. For those fetuses late in gestation with a large mediastinal shift and major cardiac and lung compression, we anticipate a difficult resuscitation due to the large size of the mass impairing resuscitation and ventilation. We deliver those cases by EXIT procedure and they require advanced ventilatory care and ECMO capability.
When you look at prenatal management of lung lesions, whether it's a CCAM, a hybrid lesion, or a BPS, the effect is due to the mass. It's a mass effect. For those on the right hand side with a large lesion, but without hydrops, treatment can be by maternal betamethasone or steroids if it's mostly solid and the CVR is greater than 1.4. And then determined by the size late in gestation will determine whether or not an EXIT or immediate resection is required. For those fetuses with hydrops at less than 30 weeks gestation, they're treated initially with maternal betamethasone if mostly solid. The fetal intervention if the betamethasone fails to help is by resection. Or for those that are macrocystic, placement of a thoracoamniotic shunt. For those at greater than 30 weeks gestation we treat by EXIT procedure. So now you're going to hear from the world famous Dr. Alan Flake who's a pioneer not only in fetal therapy, but has also really pioneered minimally invasive surgical techniques by thoracoscopy to resect lung lesions. And he's going to tell you about his clinical experience here at CHOP in great detail.
Alan Flake: Hi, this presentation will focus on postnatal management of pulmonary airway malformations.
In the prior presentation you heard about the prenatal diagnosis and characterization of congenital lung lesions. For those lesions that are prenatally diagnosed, perinatal and postnatal management can be determined by their appearance on prenatal scanning. Those lesions that have no mediastinal shift, that are small, can be anticipated to be asymptomatic. The parents can be counseled to deliver close to home. And we generally recommend a follow-up postnatal CT scan at one to two months of age with elective resection of those requiring surgery prior to three months of age. The second category are lesions that have mediastinal shift associated with them, but no major cardiac and/or lung compression. These may be symptomatic with an oxygen requirement or a minimal ventilatory requirement. They generally should deliver at a tertiary center where surgery can be offered. And postnatal resection is recommended during the neonatal admission. And finally, lesions with dramatic mediastinal shift with major cardiac and/or lung compression can be anticipated to be difficult resuscitations and should be delivered in a tertiary center that has the capability to perform the EXIT procedure and advanced ventilatory care and ECMO availability.
The postnatal management of lung lesions can be divided into three categories that share similar characteristics. The first are CPAMs, congenital pulmonary airway malformations, intralobar bronchopulmonary sequestrations, and hybrid lesions, which contain components of both. These lesions uniformly require postnatal resection, either in an elective or emergent fashion. The second category are extralobar bronchopulmonary sequestrations. These can be in any position in the mediastinum or even subdiaphragmatic or infradiaphragmatic. And depending on their position and their manifestations, they may or may not require postnatal resection. And the third group are related to the bronchial atresia sequence. They include bronchogenic cysts, bronchial stenosis, and atresia. And these can be at any level of the bronchus from the mainstem to lobar segmental bronchi. In general, the more proximal of the atresias require resection and all bronchogenic cysts require surgical treatment.
The postnatal management of lung lesions can also be considered in terms of the associated pathophysiology and histology. Congenital pulmonary airway malformations and hybrid lesions have CPAM histology, therefore, they're prone to mucostasis and infection. They have malignant potential with the most common tumors being pleuropulmonary blastomas, bronchioloalveolar carcinomas, and rhabdomyosarcomas, and they can air trap and have spontaneous pneumothoraces occur. Those are the indications for resection of even asymptomatic lesions. Intralobar bronchopulmonary sequestration may have CPAM histology and therefore may be prone to malignancies, which have been reported in these lesions. They do have mucostasis due to lack of a bronchus. However, they can communicate to the remainder of the lung via alveolar pores and therefore they're prone to pulmonary infections. There's also the potential for high flow of physiology due to their systemic vascular inflow and pulmonary venous drainage, resulting in a high-flow low-resistance circuit that may increase over time and induce cardiac failure.
As I mentioned, CPAM, intralobar BPS, and hybrid lesions all require a postnatal resection. The timing of that resection depends on their clinical manifestations. Again, lesions with mass effect, with respiratory symptoms at birth, high flow of physiology, or cardiac failure require resection in the neonatal period. Lesions that have mass effect due to air trapping that occurs after birth require a resection whenever symptoms develop. From the perspective of prevention of infections and malignancy, these tumors do not occur for many years. However, at CHOP we feel that the best time to resect asymptomatic lesions, both for prevention of infection and malignancy, is at less than three months of age.
The method of resection for lung lesions depends on a variety of factors, primarily the presentation of the patient and the skill of the operating team. Lobectomies or resections of bronchopulmonary sequestrations can be performed either thoracoscopically or by thoracotomy. Thoracoscopy has a difficult learning curve. However, the benefits are a shorter hospital stay, less pain, no thoracotomy related morbidity, and better cosmetic results in the long term. I'll emphasize thoracoscopic resection during this presentation with the understanding that large lesions or symptomatic lesions generally require a thoracotomy procedure.
I’ll now present some case presentations of various types of pulmonary airway malformations that we have take care of at CHOP.
The first case presentation is of an asymptomatic CPAM that was diagnosed prenatally. The patient is now four weeks old. And in the prenatal period had a left lower lobe CPAM diagnosed, which had a CPAM volume ratio of 0.4. So it was in the favorable prognostic category and would be anticipated to be asymptomatic at birth. At birth the patient was asymptomatic and there was no mediastinal shift. On the postnatal CT scan you can see that the lesion has persisted as a hyper-loosened area, which appears segmental in the left lower lobe.
For asymptomatic lesions, the preferred approach is thoracoscopic lobectomy. And this video demonstrates in an abbreviated fashion the basic maneuvers of a thoracoscopic lobectomy. This patient weighs approximately four to five kilograms. And you can see that we are dissecting the pulmonary artery vasculature of the lower lobe. This is done via the major fissure. And is done with single lung ventilation with approximately six centimeters of water pressure of CO2. We're using the LigaSure device to divide the pulmonary artery branches to the lower lobe. You can see the tremendous magnification that you have with thoracoscopic procedures. We've now moved on to the bronchus. We actually ligate the bronchus using intracorporeal knot tying and use a clip to secure the ligature. And then divide the bronchus with the electrocautery. This leaves only the pulmonary vein, which I also prefer to ligate at the pericardium. And LigaSure distally. And that completes the left lower lobectomy.
This is another example of an asymptomatic CPAM. Again, prenatally diagnosed with a CVR of 0.8 with a position in the right middle lobe. Again, there was no mediastinal shift and the patient was asymptomatic at birth.
And this just shows gross disease in the right middle lobe. You can see the cystic abnormality. It's apparent on the surface of the lung. There was also abnormal lobulation between the middle and the upper lobe, which is a common finding with right middle lobe lesions. This can make the thoracoscopic resection challenging due to the incomplete fissure between the lobes. Once again, you can see the dissection of the pulmonary vasculature. And the same techniques utilized for lobar resection.
This is another case of a 23 week fetus with a large left upper lobe lesion diagnosed prenatally. This was thought to be a CPAM with a CVR of 1.5. So this is a patient who was at relatively high risk for progression and potential hydrops. However, after 26 weeks the lesion regressed. And at the time of birth there was predicted to be no mediastinal shift and the patient was delivered close to home. However, tachypnea occurred at two weeks of age due to what can be seen in the postnatal CT scan here of significant air trapping in the left upper lobe. You can see the cystic disease within the lobe confirming that this is a CPAM rather than a congenital lobar emphysema. So as I mentioned, when symptoms develop in an air trapping lesion you should proceed with thoracoscopic lobectomy or a thoracotomy as soon as possible after symptoms develop.
This is another example of a CPAM that was predicted to be asymptomatic at birth. Occasionally we see bilobar CPAM. This occurs in one to three percent of patients and requires a more selective approach to resection. In this case, there was disease both in the upper and middle lobes. And the patient required a right upper and middle lobectomy at six weeks of age. In some cases, you may be better off preserving lung tissue with a segmental lung resection. For instance, if it were in the lower and upper lobes and you thought you would leave a relatively minimal amount of lung tissue following resection. However, segmental lobectomy is generally not recommended for CPAMs due to the inability to identify clearly the margins of the lesion and the risk of leaving CPAM behind, which is approximately 40 percent with segmental resections.
The next patient is an example of a prenatally diagnosed CPAM, which was a hybrid lesion. Meaning that it had both systemic arterial inflow and pulmonary arterial inflow and also had cystic abnormalities in the lung parenchyma, confirming that it's a CPAM lesion rather than an intralobar sequestration. So here on the postnatal CT scan you can see the cystic abnormalities of the lower lobe. And here on the vascular reconstruction you can see this fairly large systemic artery going up through the diaphragm into the--or into the hybrid lesion with pulmonary venous drainage back into the heart. So this has potential for high flow of physiology, eventual heart failure, as well as the potential complications of CPAM. This is another cut of the postnatal CT scan showing the extensive cystic disease in the lower lobe.
This is the appearance of the lesion on thoracoscopy. And you can see that there's marked abnormality of the surface of the lung with arterial venous communications that are sometimes seen with hybrid lesions. This is the systemic arterial inflow, which comes off of the aorta below the diaphragm. You can see it's a very large systemic arterial vessel. Again, this can be sealed with the LigaSure, which can handle vessels up to about seven millimeters in size. Hybrid lesions are managed identically to CPAMs with the exception of division of the systemic feeding vessel on the initial part of the operative procedure. And then we proceed with lobectomy. This is another hybrid lesion just showing different techniques of managing the systemic feeding vessel. This vessel comes off as a direct segmental branch from the aorta. And in this case, I'm using the endoclip for initial control of the lesion, or the artery. And then sealing the artery distal to the endoclip. And finally, here's another hybrid lesion with a large systemic feeding vessel. And in this case, we're simply ligating the vessel using intracorporeal knot tying technique. The choice of these methods depends on your skill with intracorporeal knot tying and the size of the vessel that you're dealing with. These arteries can be somewhat fragile, similar to a ductus arteriosus, and you have to take care not to tear through the vessel with the ligature.
The next case is a prenatal right upper lobe bronchial atresia that delivered prematurely at 34 weeks and 2400 grams size. You can see on the prenatal MRIs this large hyperdense lesion that actually looks a little odd in that there's a septum present. And there could almost be two lesions here, which was really not appreciated prenatally. The reason this was thought to be only a bronchial atresia is you can see this dilated cystic area in the hilar region, which is often the appearance of a bronchial atresia with distal hyperplasia due to mucus seal formation. After birth there's respiratory distress requiring four days of ventilation. And the postnatal CT scan demonstrated additional findings aside from the prenatal findings. The postnatal CT scan demonstrated a large apical sequestration, which was supplied by innominate artery branches that is systemic blood supply once again. And it also demonstrated a right middle lobe CPAM. So in this case, the prenatal diagnosis was different than the postnatal diagnosis, which is the reason that we always obtain CT scans prior to moving forward with resection.
This is the thoracoscopic appearance of these lesions. This is the right middle lobe CPAM. And this was a very peculiar upper mediastinal extralobar bronchopulmonary sequestration. You can see this pleural cap that covers the sequestration. It's common to see abnormal pleural folds in the presence of extralobar sequestrations. And here I'm removing the cap from the sequestration and that exposes the vascular bundle leading to the innominate circulation. And this is a lymph node and these are venous draining vessels from the sequestration. We will seal and divide these with the LigaSure. And then this is the arterial blood supply that we're also dividing with the LigaSure. The association of CPAM and bronchopulmonary sequestrations is not uncommon. You should always be aware of the potential for more than one lesion when prenatally diagnosed CPAMs or lung lesions present. From that point we moved on with the right middle lobectomy.
This is another case of a 21 week prenatally diagnosed patient who was thought to have a right lower lobe CPAM. And you can see this very hyperdense microcystic appearing CPAM, which is homogeneous in appearance. Now, where we can see no central area of mucus seal formation and therefore a diagnosis of bronchial obstruction was not the primary diagnosis.
Postnatally the diagnosis was once again different than the prenatal diagnosis, with a diagnosis of a mid-thoracic extralobar bronchopulmonary sequestration, which can be seen here and here, and a right lower lobe CPAM. You can see the cystic abnormality of the right lower lobe on both the sagittal and AP views.
This is the appearance of the mid mediastinal CPAM. It has a very--or extralobar bronchopulmonary sequestration. It has as a very narrow pedicle, which is easily divided using a thoracoscopic approach. And once again, after dividing the pedicle of the BPS we proceeded with the right lower lobectomy. I show these cases just to show you the variety of pathology that can be found on--in congenital lung lesions and the unusual combinations that are frequently present. Also the prenatal diagnosis does not always correspond to the postnatal diagnosis. And really the final diagnosis depends on both the postnatal imaging findings and the intraoperative and histologic findings on the lesions.
This is a important variant of CPAM. This is a four-month-old who was not prenatally diagnosed who presented to CHOP with a viral pneumonia, and this was a serendipitously identified cystic lesion in the area of the left upper lobe. On resection of this lesion it turned out to be a pleuropulmonary blastoma, which is a highly malignant lung tumor, which cannot be differentiated from CPAM either on prenatal or postnatal imaging studies. It's therefore one of the reasons that we strongly recommended resection of even asymptomatic CPAMs. I personally have had three of these in my series of CPAM patients. Two of which were prenatally diagnosed and were indistinguishable from what would be considered to be an asymptomatic CPAM.
Moving on to intralobar bronchopulmonary sequestrations. This is the prenatal diagnosis of a bronchopulmonary sequestration. You can see the posterior triangular appearance in this case, which is fairly typical. And on postnatal imaging you can see this very large feeding vessel, which has direct communication into the pulmonary vein. And in general, intralobar bronchopulmonary sequestrations have pulmonary venous drainage, whereas extralobar have systemic venous drainage. But there are exceptions to that rule. In this case, there's very minimal, if any, parenchymal abnormality of the lung and no cystic abnormality particularly, ruling out a hybrid type lesion rather than an intralobar BPS.
This is the appearance thoracoscopically of the lesion. You can see this somewhat redundant, very large systemic feeding vessel. And once again, that's divided prior to initiating the lobectomy. In this case, we're using an EnSeal device. There are a variety of sealing devices available. For most infant lobectomies, I prefer the LigaSure due to its finer tip and the ability to use it as a dissecting instrument as well as a sealing instrument. The EnSeal has the advantage of both sealing and dividing with a single instrument. But it's quite thick at its tip and therefore not useful in small areas. Now, we're just dissecting in the fissure once again to initiate the lobectomy. And we proceeded in the standard way to do the lower lobectomy procedure.
This is an older child and just demonstrates what happens if these lesions are not diagnosed or ignored. And this is an intralobar sequestration with high flow of physiology in a three-year-old and impending cardiac failure. And you can see the increased cardiothoracic ratio. You can see the very large pulmonary venous return to the heart and also a very large feeding vessel and flow through the intralobar sequestration.
So we'll move on to extralobar bronchopulmonary sequestrations. As opposed to intralobar sequestrations, they have a separate pleural investment. By definition, they have no bronchial connection and therefore there's a very low rate of infectious complications related to extralobar BPSs. They also have no alveolar communication and therefore differ from intralobar BPSs in that respect. They have systemic arterial inflow. This can be from almost any source above or below the diaphragm. They typically have systemic venous drainage, but can have pulmonary venous drainage. And this is a situation where a high outflow--or a high flow of physiology is particularly likely to evolve because of the low resistance of the pulmonary vascular circuit. And then, again, they can be supra, intra, or subdiaphragmatic in position. Pinnacle considerations are that they may have CPAM histology and this is usually manifest on imaging studies by visible cysts. They can have mucostatis, but with no communication, minimal risk of infection, again, potential for high flow of physiology. And extralobar sequestrations with narrow pedicles can have lymphedema and pleural effusion. And this can be a presentation that induces hydrops prenatally, requiring thoracoamniotic shunting. And finally, an occasional esophageal bronchus is found with extralobar sequestration that lie adjacent to the bronchus.
The reasons for resection or the indications for resection of extralobar BPS are shown here. Again, high flow of physiology or the potential to develop high flow of physiology, that goes along with a large systemic feeding vessel. If they have initially large size or integral growth, they should be resected. Visible cysts by ultrasound or CT scans suggest CPAM histology and a risk for malignancy and therefore we recommended resection. And finally, those presenting with pleural effusions should be resected.
I'll show you some examples of various types of extralobar BPS.
This is a fairly typical appearing extralobar BPS. You can see its triangular shape on prenatal imaging studies with normal posterior inferior position. And on the posterior CT scan you can see this density that corresponds to its prenatal appearance as well as subdiaphragmatic systemic arterial inflow from the celiac axis.
This is the appearance of this lesion on thoracoscopy. You can see this is the edematous variant. You can see the tissue edema within the BPS and this is usually related to a very narrow pedicle, as you'll see. It has a narrow pedicle and probably venous and lymphatic congestion, which cause the edema and sometimes the pleural effusion. These are very easily managed by thoracoscopic resection, which is the indication--or the procedure of choice with extralobar BPS. And again, it's just a matter of isolating the vessels, sealing them by whatever technology, and dividing them. This is a very easy procedure and can essentially be performed of an overnight hospital stay.
This is a five-week-old prenatally diagnosed asymptomatic BPS. But as you can see, it's very large in size with displacement of the mediastinum and adjacent lung tissue. That's the indication for a resection of this lesion.
This is the thoracoscopic appearance of this very large BPS. Once again, it's of the edematous variety and you can see some associated pleural effusion. It's also got a very small pedicle, as expected. And once again, it's a matter of simply isolating the vessels, dividing them by whatever technology, and removing the lesion. You can see how edematous it is and the associated pleural effusion here.
This is another example of a extralobar BPS. This was prenatally diagnosed. The patient is now five weeks old and had his postnatal CT scan. And you can see that this lesion is a little unusual in that it's very low in the posterior sulcus, very close to the esophagus, and really in the area of the esophageal hiatus. With these lesions you always need to suspect that they can be infra or subdiaphragmatic. And you also need to suspect the presence of an esophageal bronchus.
In this case, a esophageal bronchus was identified. Here you can see we're dissecting down on the pedicle of the BPS. Here's the BPS. Here's the diaphragm. So the lesion is right down against the diaphragm in the esophageal hiatus. There's extensive blood supply in the pedicle coming from beneath the diaphragm. That's a feeding artery. As we come down, the remaining pedicle develops a bronchial appearance. I've now ligated this with a endoloop against the esophagus, which is here. And you'll see that as we open the bronchus it's filled with purulent mucoid material. These often get infected as their mode of presentation.
This case shows an extralobar BPS with azygos venous drainage. So it's systemic arterial inflow and venous drainage into the azygos vein. You can see this smoothly contoured, posterior--contoured, posterior lesion in the postnatal CT scan. And it's bright due to the high blood flow within the lesion on this contrast enhanced CT. These are the arterial inflow vessels coming across the mediastinum from the aorta. And this is the azygos venous drainage that you can see coming out of the lesion and up the edge of the mediastinum and the azygos vein. Once again, here's the lesion in cross section. And you can see the aortic arterial inflow crossing over and the azygos venous drainage.
And this is the thoracoscopic appearance of the lesion. You can see this jumble of blood vessels. And this is the vein that I'm taking first because it's on top of the artery. And this is heading up into the azygos vein. And that exposes this very large systemic feeding artery. And you can see the tremendous blood flow through this lesion despite the relatively small size. So these are cases that require a resection to prevent high flow of physiology in the future and cardiac failure.
This is an example of an extralobar BPS with pulmonary venous drainage. So as opposed to most BPSs, which have systemic venous drainage, this actually has this very unusual appearing anomalous vein that extends upward and drains into the superior pulmonary vein.
And here it is, a fairly typical appearing BPS. And you can see this very large anomalous venous drainage that's going into the lung parenchyma and ultimately draining into a pulmonary vein. And here's the systemic arterial inflow, shown here, coming off the aorta, and the pulmonary venous outflow. Once again, the potential for high flow of physiology is the indication for resection.
This case is a hybrid lesion, which anatomically appeared to be more of an extralobar bronchopulmonary sequestration. Again, there's a spectrum of both gross and histologic pathology, and this is an example of that. So on imaging studies you see the cystic abnormality in the left lower lobe. And on the vascular reconstruction you can see the aorta coming down and this--these multiple arterial feeding vessels that are coming into the lesion. There's also pulmonary venous drainage, as show here, and azygos/IVC venous drainage.
So here's another case of extralobar BPS that shows pulmonary venous drainage. This is the prenatal appearance on prenatal MRI. And you could see this abnormal vessel here that courses into the lesion. Now, prenatally it was not apparent whether this was a microcystic CPAM or whether this represented some form of sequestration. On the postnatal CT scan you can see this very large blood supply and lesion. And here's the pulmonary venous drainage. On the lower image here you can see the large systemic arterial supply that goes over to the aorta. And then here's the pulmonary venous drainage. And once again, here's the arterial blood--or inflow to the aorta.
This shows the thoracoscopic appearance of the lesion. This is the very large extralobar sequestration. And I'm examining the pedicle. You can see this huge venous channel that's going directly into the inferior pulmonary vein though the lung parenchyma. And then examining the other side you see the very large systemic arterial inflow going into the lesion.
This is another variant of extralobar BPS, and that's subdiaphragmatic BPS. This was prenatally diagnosed as a subdiaphragmatic mass. Patient had a CT scan at five weeks of age and had been somewhat symptomatic with slow feeding and frequent spitting up since birth. And here you can see this mass in the subdiaphragmatic area and in the region of the esophageal hiatus. You can see systemic feeding vessels coming off of the celiac axis. And this shows that in a vascular reconstruction. Here's the vascular mass and feeding vessels coming off of the celiac axis.
This is the laparoscopic appearance. Again, this is subdiaphragmatic, so we're going through the abdomen for its resection. We're looking at the spleen here. Looking into the lesser sac. This is the stomach on the left side. And this is the mass in the retroperitoneum heading up into the esophageal hiatus. Here's your diaphragm. You can see how this mass could easily compress the region of the gastroesophageal junction and cause difficulty with feeding. Mass was very vascular with numerous feeding vessels. We also had to separate it from the pancreas and the spleen. It was also somewhat inflamed. On the imaging studies you saw earlier there was a cystic area in the middle of the mass that turned out to be CPAM histology. So here we have a infralobe--or infradiaphragmatic extralobar BPS with compression of the gastroesophageal junction and also a CPAM component within the lesion, making it at risk for ultimate malignant degeneration. That was division of the primary systemic feeding vessel and now we're excising it from the esophageal hiatus. Had to follow it up into the hiatus. And ultimately we had to reapproximate the diaphragmatic crura to tighten the hiatus around the esophagus. There we go. And here you can see the defect in the hiatus and we close that with a few sutures. Again, this was densely adherent to tissue circumferentially. It was actually fairly tedious to remove. And here it's finally free of surrounding structures.
So the next topic are bronchogenic cysts and the bronchial atresia sequence. Bronchogenic cysts can be isolated or they can be associated with the bronchus, which leads to bronchial obstruction, damage to the bronchial wall, and lobar hyperplasia distal to the level of obstruction. Bronchial atresia, similarly, causes massive lung hyperplasia if it's proximal in location. Particularly mainstem bronchial atresias will cause the entire lung to be massively hyperplastic and often induce fetal hydrops, and it's almost a uniformly lethal anomaly. Lobar bronchial atresia results in lobar hyperplasia, which may require a resection prenatally or postnatally depending on whether it induces hydrops in the fetus. Segmental bronchial atresia is a more recently identified entity. You often have bronchiolar or alveolar ectasia, mucostasis in the area of the lesion, and they can contain CPAM elements. Bronchial stenosis can be similarly mainstem, lobar, or segmental. And you can have lung or lobar air trapping, hyperaeration, or bronchiolar or alveolar ectasia, and can have CPAM elements.
Bronchogenic cysts generally require a resection, although they can be observed and resected once they are documented to increase in size. If they're in a location where they compromise adjacent structures then they obviously require early resection. Bronchial atresia can be mainstem or lobar. Generally require a resection in the neonatal period. Occasionally requires sleeve resections, pneumonectomies, or lobectomies. Segmental bronchial atresia can generally be managed in a elective fashion and resected at less than three months of age. Bronchial stenosis, again, it depends on the level of the lesion. Requires a resection if symptomatic. Sleeve resections for mainstem bronchial stenosis. Dilation or stents are alternative approaches. And then segmental bronchial stenosis can occasionally be observed. However, if cystic changes are present it suggests the presence of CPAM elements and the need for a resection.
Here are a few cases of either bronchogenic cysts or atresias.
This is the appearance of a bronchogenic cyst. Cystic structure in the hilar area of the lung, and you can see the distal lobar hyperplasia and sometimes hyperinflation. And here you can see an edematous--or a emphysematous right upper lobe.
This is the appearance by a thoracoscopy. Typically, when you see hyperplasia distally there's damage to the bronchus. The bronchogenic cyst is not separable from the bronchus and you require--they require a lobectomy for treatment. Here you can see the bronchogenic cyst in the hilum. It's typically beneath the pleura and often surrounded by pulmonary arterial structures with the bronchus sitting posteriorly. Here are arterial branches to the upper lobe. Again, we're using the EnSeal to seal and divide the vessels. And that will expose the underlying cyst, which can now be seen fairly clearly. And here we're proceeding with the lobectomy.
This final case is a case of the extreme of bronchial atresia, which is a mainstem bronchial atresia. This was diagnosed in utero. You can see this massive lung hyperplasia with a central area of bronchial dilation. And that's the tip off that this represents a bronchial atresia rather than a microcystic CCAM. You can also see the marked ascites within the abdominal cavity and a small amount of skin and scalp edema consistent with hydrops in this fetus.
The fetus was followed and over time the hydrops resolved. This is a later gestational MRI. However, this very large, hyperdense, hyperplastic lung remained. This fetus was delivered by the EXIT procedure and immediately placed on ECMO. However, due to the severe pulmonary hypoplasia of the contralateral lung and hyperplasia of the ipsilateral lung, there was ultimately no treatment that was successful and the infant ultimately expired. There have been no documented survivors of mainstem bronchial atresia up to this time, and it's generally a lethal anomaly. So that concludes a general overview of congenital pulmonary airway malformations and their postnatal management. Thank you for your attention.