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Congenital pulmonary airway malformation (CPAM) is a relatively uncommon condition. It affects only 1 in approximately 4,000 babies born each year and involves lung lesions or masses that form in a baby's lower respiratory tract.
As a parent, it can be overwhelming to discover your child has this condition. Fortunately, the Colorado Fetal Care Center has a large team of multidisciplinary fetal care specialists who are here for you from the initial diagnosis to continuing care after delivery.
Congenital pulmonary airway malformation (CPAM) is the newer term for what was previously known as congenital cystic adenomatoid malformation (CCAM). It is part of a variety of conditions that involve cystic lung lesions or masses that form in the lower respiratory tract during a baby's development.
These are typically noncancerous masses that occur most commonly in one lung rather than both lungs, though any lobe of either lung may be affected.
The condition is found more commonly in males than females. It occurs because of an alteration in the lung development very early in pregnancy (about 8-9 weeks), though the exact cause is not known. It is not thought to be genetic, as no cases of recurrence of congenital pulmonary airway malformation in a sibling or offspring have been reported.
Depending on the size, the malformation can grow rapidly, causing a shift in structures within the chest (e.g. heart, lung, esophagus) which may not allow the baby to develop normally. In other cases, the mass may also compress the esophagus, causing amniotic fluid to increase, which puts the mother at risk for preterm labor.
The impact a malformation has on your baby will differ greatly depending on the size of the mass, its location and whether it impacts other organs in the chest cavity. Larger lesions can cause fetal hydrops (excessive fluid buildup) due to shifting in the chest and compression of the large vein (vena cava) that returns blood to the right side of the heart.
Maternal "mirror syndrome" can also develop in cases of fetal CPAM. In these cases, the mother accumulates excessive fluid similar to the fetus, as well as very high blood pressure (preeclampsia). Though quite rare, this condition would require immediate delivery.
The worst risk with congenital pulmonary airway malformation, however, is the immediate period of time before birth. If air becomes trapped within the cystic tumor, it can cause serious respiratory distress in the soon-to-be-born baby. After birth, ongoing cysts can result in recurrent bouts of pneumonia and other respiratory infections. Collapse of the lung (pneumothorax) is also an additional concern. In rare cases, some CPAM lesions can become cancerous.
In pregnancy, this mass is detected during an ultrasound examination, where it shows up as a bright area in the lung. It is generally a benign mass that will have no impact on the pregnancy itself. However, there are characteristics of the mass that could make it dangerous to a developing fetus and newborn, including the size of the mass and how cystic (dense) the mass is.
Depending on the type of malformation, the mass may appear similar to other conditions including diaphragmatic hernia, cystic hygroma or other cystic lesions. Because CPAM masses need to be differentiated from other lung masses and conditions, your baby should be evaluated with a detailed ultrasound and fetal MRI in order to determine the best next steps.
Because of the wide degree of severity of cysts and lesions associated with congenital pulmonary airway malformation, treatment plans vary just as widely. Depending on how the condition is impacting the baby, treatment options can range from surgery to specific support after delivery.
The Colorado Fetal Care Center is one of the most experienced and trusted fetal care centers when it comes to diagnosing and treating babies with congenital pulmonary airway malformation. Our state-of-the-art facility offers the best standards in treatments, as well as the best outcomes for babies diagnosed with congenital pulmonary airway malformation.
Congenital pulmonary airway malformation treatment, in general, includes monitoring, fetal intervention and surgery after birth:
After diagnosis, the fetus will be monitored with frequent ultrasounds to determine the growth of the mass and whether the mass is affecting surrounding organs. Other diagnostic tests might be ordered to rule out concurrent conditions. Often a detailed ultrasound of the fetal heart (fetal echocardiogram) is performed to assess the heart structures as well as how those structures are functioning.
Our team of fetal CPAM experts have extensively researched measurements and outcomes to determine indicators that predict which babies could potentially benefit from in utero treatment. During their research, they found that fetuses with CPAM, a dominant cyst and hydrops developed prior to 32 weeks may be candidates for treatment in utero.
Using ultrasound or other imaging methods to view the fetus and cyst, a thin tube (called a shunt) can be directly inserted into the cyst and left in place to drain the cyst into the amniotic fluid. This will cause the cyst to shrink and stop or decrease the accumulation of fluid in the fetus.
Some cases of CPAMs have multiple cysts that require fetus thoracoscopy to break up the cysts before the shunt can be placed. There is also a subset of patients who might benefit from open fetal surgery, whereby the CPAM is surgically removed from the fetal chest while still in the mother’s uterus.
Surgical treatment post-birth
Some cases of CPAM will regress spontaneously before birth, which is why monitoring mass growth is so important before deciding on surgical treatment. Careful postnatal evaluation is also important to ensure complete regression, however, if the mass is not removed before birth. Subtle abnormalities might be evident on a chest X-ray, but a chest CT or MRI may be necessary to detect residual CPAM tissue.
Complete resection of the CPAM mass, usually by the removal of the entire affected lung lobe (lobectomy), is the treatment of choice for CPAM if cysts or masses are still found after initial treatments.
The long-term outcome for infants following CPAM surgery is excellent. Infants usually have remarkable growth of lung tissue that remains following surgery, which usually compensates for the portion of lung that was removed (if any).
If your child was diagnosed with congenital pulmonary airway malformation, you probably have a lot of questions. The Colorado Fetal Care Center can help answer them. Learn more about the Colorado Fetal Care Center, including our latest outcomes and the location of a fetal care center near you.
CPAM is diagnosed by prenatal ultrasound demonstrating a lung tumor that may be solid or cystic and with an absence of systemic vascular flow. Types I and II CPAM appear as cystic or echolucent pulmonary masses and may appear similar to diaphragmatic hernia, cystic hygroma, and other cystic lesions, such as bronchogenic or enteric or pericardial cysts. In contrast, type III CPAM typically appears as a large hyperechogenic mass, often associated with mediastinal shift and, in advanced cases, hydrops.
The sonographic appearance of CPAMs can range from solid echodense mass filling the chest to a lesion with a single dominant cyst with a compressive effect on the mediastinum. The vast majority of CPAMs derive their blood supply from the pulmonary circulation and drain via the pulmonary veins. However, color Doppler should be used to search for the presence of a systemic feeding vessel. This may be observed in most BPSs (the main differential diagnosis in CPAMs) and in “hybrid” CPAM lesions (Cass et al., 1997). The systemic feeding vessel in hybrid CPAM lesions usually comes directly off the descending aorta; however, transdiaphragmatic systemic feeding vessels have also been observed in CPAMs.
A change in the echogenicity of type III CPAMs may occur between 30 and 34 weeks in which they become isoechogenic with adjacent normal lung. Although sonographically invisible, such cases of CPAM are still readily apparent on MRI. Occasionally, postnatal imaging with CT scanning reveals no evidence of CPAM, which may be due to the presence of lobar emphysema instead.
The differential diagnosis of fetal thoracic masses includes congenital diaphragmatic hernia (CDH), bronchogenic or enteric cysts, BPS, mediastinal cystic hygroma, bronchial atresia or stenosis, neuroblastoma and brain heterotopia. The sonographic appearance of CPAM will influence the differential diagnosis. Type I CPAMs are more likely to be confused with a CDH. Observing peristalsis in the loops of herniated intestine or emptying of the stomach herniated through the diaphragm may help to differentiate the two (May et al., 1993). In rare cases in the past, amniography and computed tomographic (CT) scanning have been employed to distinguish CDH from other thoracic lesions (Adzick, 1993). More recently, fetal magnetic resonance imaging (MRI) has proved extremely helpful in evaluating fetal chest masses and distinguishing them from diaphragmatic hernia (Hubbard and Crombleholme, 1998). It is also worth noting that there have been cases of CPAM occurring in association with CDH (Stocker et al., 1977). The microcystic type III CPAMs are highly echogenic. This is helpful in distinguishing CPAM from solid tumors such as neuroblastoma. Bronchogenic cysts are unilocular and are usually adjacent to major bronchi, which may be confused with a type I CPAM.
However, the main differential diagnosis in CPAM is usually BPS. Unlike most CPAMs, BPS derives its blood supply from the systemic circulation (Carter, 1959). This systemic blood supply to BPS can often be demonstrated with the use of color flow Doppler studies (Hernanz-Schulman et al., 1991; Morin et al., 1994). In older literature, there is an anecdotal report of CPAM associated with anomalous blood supply (Rashad et al., 1988). With the exception of this case, the demonstration of systemic blood supply to a thoracic mass has been thought to be pathognomonic of BPS. More recently, Cass et al. (1997) described six cases of cystic adenomatoid malformation that had systemic blood supply. These lesions were called “hybrid” lesions as they had features of both CPAMs and BPSs and their natural history was also a mixture of the two lesions. The prognosis in hybrid CPAM is more favorable than CPAMs without a systemic feeding vessel (Crombleholme et al., 2002).
The postnatal natural history of CPAM can be quite variable. The lesion can be completely asymptomatic and come to medical attention only when chest radiography is performed for other reasons, such as a history of mild respiratory complaints with recurrent infections in infancy or childhood (Stocker et al., 1977). However, fewer than 10% of CPAMs present after the first year of life. Eighty percent of symptomatic postnatal patients present at birth with severe cardiorespiratory compromise due to severe pulmonary hypoplasia (Atkinson et al., 1972; Cloutier et al., 1993; Heij et al., 1990; Hernanz-Schulman et al., 1991; Kuller et al., 1992; Neilson et al., 1991; Nishibayashi et al., 1981; Pulpeiro et al., 1987; Stocker et al., 1977). Even before the advent of obstetrical sonography, it was recognized that up to 14% of cases of CPAM result in stillbirths (Stocker et al., 1977). This observation hinted at the different prenatal natural history of CPAM.
The outcome of fetuses diagnosed prenatally with CPAM has only recently been reported and our understanding of the natural history of CPAM is still evolving. We know that the worst outcome is observed in fetuses in which hydrops develops (Adzick, 1993; Adzick et al., 1985B, 1998; Harrison et al., 1990A). Hydrops is usually seen in very large lesions, often type III lesions, which cause mediastinal shift and vena caval obstruction. Hydrops may also be exacerbated by the loss of protein from the CPAM into the amniotic fluid, thus reducing the fetal colloid oncotic pressure from hypoproteinemia (Hernanz-Schulman et al., 1991). There are only anecdotal reports of a fetus with CPAM surviving after the onset of hydrops. Ten cases have been reported of CPAM associated with hydrops in which 4 of 10 ascites was the only manifestation of hydrops and all resolved spontaneously (Diamond et al., 2003; Bunduki et al., 2000; Domergeres et al., 1997; Etches et al., 1994; Graham et al., 1982; Glenes et al., 1983; Heydanes et al., 1993; Highy et al., 1998; Meager et al., 1993). Diamond et al. suggested that resolution by 30 weeks’ gestation may be more common than is appreciated. The reason for this unexpected resolution of hydrops in CPAM was not apparent until the natural history of CPAM was better defined by Crombleholme et al. (2002). CPAMs plateau in their growth at an average of 26 weeks’ gestation after which the fetus grows around the CPAM allowing hydrops to resolve (Crombleholme et al., 2002).
Adzick et al. have proposed a modification of Stocker’s classification of CPAMs based on anatomy and sonographic appearance to assist in predicting outcome in cases detected in utero (Adzick et al., 1985B). In this classification, macrocystic CPAMs have single or multiple cysts >5 mm in diameter. Microcystic CPAMs are more solid and bulky, with cysts that are <5 mm in diameter. This distinction can easily be made sonographically in the fetus. Macrocystic lesions appear sonographically as fluid-filled cysts while microcystic lesions appear solid due to fine interfaces with the ultrasound beam creating an almost homogeneous appearance (Adzick et al., 1985B). This is a useful sonographic distinction because microcystic lesions may be at increased risk for the development of hydrops. The high mortality rate of microcystic lesions is due to the large size these lesions attain and secondary sequelae, including mediastinal shift, pulmonary hypoplasia, polyhydramnios and nonimmune hydrops (Adzick et al., 1985B, 1993, 1998; Harrison et al., 1990A). Despite the type of lesions, however, the overall prognosis depends primarily on the size of the lesion. Polyhydramnios is seen in up to 70% of CPAMs diagnosed antenatally (Adzick et al., 1998). The pathogenesis of polyhydramnios is not completely understood but is thought to relate to esophageal obstruction from mediastinal shift and interference with fetal swallowing of amniotic fluid (Miller et al., 1980; Murayama et al., 1987). This is supported by the absence of fluid in the stomachs of many of these fetuses.
The diagnosis of CPAM may also have implications for the health of the mother. Adzick et al. (1993) reported a mother with a fetus with CPAM that developed the “mirror syndrome,” a hyperdynamic pre-eclamptic state that may be life-threatening. The “mirror syndrome” has been seen in molar pregnancies, sacrococcygeal teratoma and in fetal conditions that result in poor placental perfusion which leads to endothelial cell injury (Roberts et al., 1989; Creasy, 1979). The only treatment for this syndrome is immediate delivery of the baby and placenta.
The antenatal diagnosis of a large CPAM might at first appear to be an ominous finding; however, several reports have described disappearing fetal lung masses (Adzick and Harrison, 1993; Adzick et al., 1993; Budorick et al., 1992; Fine et al., 1988; MacGillivray et al., 1993; Saltzman et al., 1988). MacGillivray et al. (1993) have reported six cases of large CPAMs with associated mediastinal shift that progressively decreased in size over the course of gestation. These lesions were all of the microcystic or type III variety but none were associated with nonimmune hydrops. The percentage of cases that will undergo spontaneous regression is not known for certain but the experience at two tertiary-care centers was between 6 and 11% of evaluated cases (Adzick et al., 1998; MacGillivray et al., 1993). The reason for regression of fetal CPAM is not understood. Decompression of the fluid from the CPAM into the tracheobronchial tree or outgrowing its blood supply has been suggested as possible mechanisms (Adzick et al., 1993). There has been no biochemical or sonographic marker that allows us to distinguish between CPAM that will regress and one that will progress to hydrops. There is a change in the echogenicity of type III CPAMs between 30 and 34 weeks in which they become isoechogenic with adjacent normal lung. Although sonographically invisible, CPAMs are readily apparent on MRI. Occasionally, postnatal imaging with CT scanning reveals no evidence of type III CPAMs. It is likely that the diagnosis in these cases is not CPAM but segmental or lobar hyperinflation.
Crombleholme et al. (2002) reported the use of CPAM volume and the CPAM volume ratio at presentation as a predictor of the development of hydrops. The CPAM volume is calculated using the formula for the volume of an ellipse (h × w × l × 0.52) in cm3 with the measurement of the greatest length in the saggital section and the width and height taken at 90 degrees to the saggital measurement. The CPAM volume ratio (CVR) is obtained by dividing the CPAM volume by the head circumference (in cm) to correct for any differences in gestational age. Based on 32 fetuses with CPAM, the CPAM volume and the CVR were found to be significantly higher in fetuses who had or would develop hydrops. In addition, when the mean of the group that did not develop hydrops plus two standard deviations were added a cutoff value of 1.6 was obtained. In a prospective study of 42 fetuses with CPAM, only 2% of fetuses with CVR <1.6 (and no dominant cyst) developed hydrops. Of those fetuses with CVRs >1.6, 80% developed hydrops (Crombleholme et al., 2002). The CVR is a useful criterion to select fetuses at greatest risk for the development of hydrops and those at low risk for development of hydrops.
One of the largest experiences with prenatally diagnosed CPAM has been reported by Adzick, Harrison and Crombleholme (1998). This series reflected the combined experience of the Center for Fetal Diagnosis and Treatment at the Children’s Hospital of Philadelphia and the Fetal Treatment Center at the University of California San Francisco, comprising a 12–year retrospective study at the two centers and 175 fetal lung lesions. There were 134 fetuses with CPAM in this group. Of these, 14 pregnancies were terminated, 101 cases were managed expectantly, 13 women underwent open fetal surgery and 6 fetuses underwent thoracoamniotic shunt placement. In the fetuses that did not develop nonimmune hydrops, the postnatal survival was 100%. In contrast, of 25 large CPAMs that developed hydrops and were managed expectantly, there was 100% mortality, with death in utero or immediately after birth. Among the 76 fetuses with CPAMs that were not associated with hydrops, the uniform survival was, in part, due to planned near-term delivery at a tertiary-care center. Many of the babies with large lesions required substantial ventilatory support and four needed the support of extracorporeal membrane oxygenation (ECMO).
Fifteen CPAM lesions appeared large at 20–26 weeks of gestation with an associated contralateral mediastinal shift, but then clearly decreased in size during the third trimester with return of the position of the heart toward midline. Although four of these shrinking lesions were associated with polyhydramnios, including one case with fetal ascites, these phenomena resolved as the masses decreased in size.
The presentation of CPAM is quite variable and can extend from the early prenatal period to late in adult life. The spectrum runs from an incidental finding on a routine chest X-ray in a completely asymptomatic patient to severe respiratory distress in the newborn period. More and more of these lesions are now picked up in the prenatal period on routine screening ultrasound, allowing for prenatal consultation and planning.1 The findings on ultrasound ranges from an incidental finding of a cystic appearing lesion to massive pulmonary involvement with the development of hydrops.2 Hydrops can develop in up to 40% of cases and regression of the lesion is seen in up to 60 % during the course of gestation. The need for fetal intervention is rare and limited to those cases with severe hydrops unresponsive to steroids with a predicted mortality of near 100%. The differential diagnosis of CPAM includes other cystic diseases of the lung including bronchopulmonary sequestration (BPS), bronchogenic cyst and segmental or lobar hyperinflation. The primary differentiation between CPAM and BPS are based on 2 anatomic points. BPS has no connection to the tracheobronchial tree and are supplied by an anomalous systemic artery. CPAMs are usually not. However, the difference between the 2 lesions is not as discreet as once thought and it is more likely that the 2 are variants of the same abnormal developmental pathway. Prenatal diagnosis is usually made by ultrasonography and generally classified into two categories: microcystic lesions with cyst <5mm which appear echogenic and solid and macrocystic lesions of one or more cysts >5mm.3 MRI is also being used more frequently to examine the fetus and can help differentiate CPAM from other thoracic lesions including congenital diaphragmatic hernia, foregut duplications and others. In the neonatal period, the diagnosis is usually suspected based on clinical presentation and the initial chest x-ray. A CT scan is usually definitive, although the exact diagnosis may not be made until surgical exploration is performed. Diagnosis later in life is usually dependent on late symptoms or in some cases an incidental finding on a routine CXR. CT scan is still the gold standard.
1 Taguchi T, Suita S, Yamanouchi T, et al. Antenatal diagnosis and surgical management of congenital cystic adenomatoid malformation of the lung. Fetal Diagn Ther 1995;10:400-405
2 Miller JA, Corteville JE, Langer JC. Congenital cystic adenomatoid malformation in the fetus: natural history and predictors of outcome. J Pediatr Surg 1996; 31:805-808
3 Adzick NS, Harrison MR, Crombleholme TM, et al. Fetal lung lesions: management and outcome. Am J Obstet Gynecol 1998; 179: 884-889
The management of CPAM depends on the CVR value that is obtained at presentation. If the CVR is less than 1.6 and there is no evidence of a dominant cyst, the CPAM has only a 2% risk for the development of hydrops (Crombleholme et al., 2002). The fetus should have weekly sonograms to measure the CPAM volume and CVR in order to identify early signs of hydrops or more likely that the plateau in growth had been reached. Once the growth plateau is reached, the pregnancy is no longer at risk for the development of hydrops. The surveillance of the fetus can be reduced but one should continue to assess the size of the CPAM, as well as the risk of pulmonary hypoplasia or air trapping which would influence delivery management.
If there is a dominant cyst, even if the CVR is <1.6, the fetus remains at significant risk for acute enlargement of the cyst and development of hydrops. A thoracoamniotic shunt may be considered in these cases at the very earliest sign of hydrops.
If the CVR is >1.6 at presentation, with or without a dominant cyst, there is up to an 80% chance of hydrops developing. Twice weekly sonographic surveillance should be started to help detect the earliest signs of hydrops in which case fetal surgery may be considered. Also with a CVR of >1.6, a course of maternal steroids (betamethasone) should be considered. There are several small series documenting resolution of hydrops in patients with CPAMs that were not candidates for open fetal surgery who were treated with steroids (Tsao et al., 2003; Parenteau et al., 2006). It is thought that steroids may arrest the growth of the solid component of the CPAM inducing an early growth plateau allowing the fetus to grow around the CPAM and hydrops to resolve. It is not proven that steroids truly affect the growth of CPAMs and the observations reported may be due to the CPAMs naturally entering the plateau independent of the steroids. Not all CPAMs respond to steroids, however. We have treated 42 cases with maternal steroids with significant progression in two cases despite initial improvement. Both went on to open fetal surgery. If steroids are to be administered for hydropic CPAM, it is prudent to do so in conjunction with consultation with a fetal surgery center.
Fetuses with CPAM and a dominant cyst in which hydrops develops prior to 32 weeks can be considered for treatment in utero. Nicolaides et al. (1987) reported the first case of CPAM treated in utero. Decompression of a very large cystic lung lesion in a 20-week-old fetus by percutaneous placement of thoracoamniotic catheter shunt was reported by Clark et al. in 1987. This procedure resulted in resolution of both mediastinal shift and hydrops and successful delivery at 37 weeks of gestation. Postnatally, the infant underwent uneventful resection of the CPAM. Six subsequent cases have been reported by Adzick et al., with favorable outcome in five of the six fetuses treated (Adzick et al., 1993, 1998). Wilson et al. reported an additional 10 cases treated with thoracoamniotic shunting with 70% survival (Wilson et al., 2004). There now have been at least 28 cystic CPAMs treated by thoracoamniotic shunting (Bernoschek et al., 1994; Miller et al., 1996; Dommergues et al., 1997; Bunduki et al., 2000; Laberge, 2001; Wilson et al., 2004; Viggiano et al., 2004) with survival of 19 of 27 or 70.4%. It is important to note that despite successful decompression by thoracoamniotic shunting, survivors often have marked respiratory insufficiency and some have required ECMO or high-frequency ventilation. These cases are unusual in that hydrops developed in macrocystic lesions. The most worrisome antenatal presentation is a large microcystic CPAM with hydrops that does not lend itself to catheter decompression. Fetal surgical resection of massively enlarged microcystic CPAM with associated hydrops has been performed in 25 patients at 21 to 29 weeks of gestation (Adzick et al., 1993, 1998; Harrison et al., 1990B). In one case, a multicystic lesion underwent thoracoamniotic shunt placement which failed to adequately decompress the mass effect prior to fetal surgery. In the 16 fetuses that survived, fetal CPAM resection led to hydrops resolution in 1 to 2 weeks, return of the mediastinum to the midline within 3 weeks and impressive in utero lung growth. There were nine fetal deaths in the cases of fetal surgery resection. In one case, the “mirror syndrome” had already developed in the mother (Creasy, 1979). The fetal operation was successful, and the hydrops improved but the placentomegaly and maternal hyperdynamic state remained and the fetus was delivered 1 week later. In one case, the fetus had bradycardia and died 8 hours postoperatively. In another case, uncontrolled uterine contractions were the cause of intraoperative fetal death. In the remaining deaths, massive hydrops was present and the fetuses died intraoperatively, one during induction of anesthesia and the others immediately after the fetal thoracotomy was performed with terminal bradycardia after delivery of the CPAM from the chest.
Open fetal surgery remains a treatment option for type III CPAMs associated with hydrops refractory to maternal steroids, some patients either won’t be candidates for open fetal surgery because of medical or psychosocial contraindications or due to reservations regarding maternal risks of the procedure. In these cases, one or more courses of maternal steroids (betamethasone or dexamethasone) may be effective in arresting the growth of the CPAM. We have treated 42 patients in the Colorado Fetal Care Center with resolution of hydrops. The fetus remains at high risk, however, for significant pulmonary hypoplasia. In some instances, the size of the CPAM remains substantial with significant mediastinal shift and cardiac compression. In these cases, delivery by EXIT-to-Resection may be indicated (Hedrick et al., 2005). The rationale for this approach is that the mediastinal shift and compression by the CPAM will make ventilation difficult if not impossible and will similarly impair venous return if ECMO was attempted. During EXIT-to-Resection, a thoracotomy for resection of the CPAM usually by formal lobectomy is performed on placental support. In this approach, when the infant is born, the trachea is decompressed facilitating ventilation and, if ECMO is needed, venous return to the cannular will be unobstructed.
It was empirically observed that treating mothers with betamethasone could arrest the growth of some CPAMs. We reported a series of CPAMs of varying types (Morris et al. 2008) and found a 50% response rate among 4 cases of high risk CPAMs. In collaboration with UCSF and CHOP, we pooled our cases and determined that in type III or microcystic CPAMs, there was an 85% response rate but type I or II CPAMs had a significantly lower response rate. We have experience with 54 CPAMs treated prospectively with betamethasone for CPAMs with CVR > 1.6 and/or hydrops. In patients with CPAMs with CVR > 1.6 but no hydrops, survival was 100%. Even in hydropic CPAMs, 49% responded to steroids with resolution of hydrops and survival. In the 6 cases that did not respond to one course of steroids a second course was successful in 2 of 6. If the CPAM does not respond to 2 courses of steroids the best alternative is open fetal surgery.
At the Colorado Fetal Care Center we treat all CPAMs with a CVR > 1.6 or evidence of hydrops with a course of 2 doses of 12 mg of betamethasone. These high risk CPAMs are followed 2 to 3 times a week. Response is defined as plateau in growth of CPAM. The natural history of CPAM is that a plateau in CPAM growth occurs at a mean gestational age of 26 weeks. We believe that steroids induce arrest of CPAM growth, resulting in a plateau earlier than might otherwise occur. The fetus then grows around the CPAM and gradually the hydrops resolves.
We have observed that, while CPAMs may stop growing, some large lesions don’t regress as readily as less high risk CPAMs. For this reason, we have seen more CPAMs remain quite large with compromise of the intrathoracic airway requiring delivery by Exit-to-Resection. It is essential that these CPAMs having responded to steroids be followed very closely and reassessed for the compromise of the intrathoracic airway and need for delivery by Exit.
The infant with type I, II or IV CPAM may be at significant risk for air trapping in the CPAM, which may acutely worsen respiratory status (Stocker et al., 1977; Bailey et al., 1990). In cases of unilateral CPAM, selective intubation of the contralateral bronchus may be a useful temporizing measure until resection of the CPAM can be accomplished. Pneumothorax is an additional concern in CPAM, especially in the type I or II lesions, and may require tube thoracostomy (Bentur et al., 1991). CPAM is usually confined to a single lobe. Rare cases have been reported of multilobar involvement of one lung or bilateral lesions (Rempen et al., 1987). Complete resection of the CPAM, usually by lobectomy, is the treatment of choice in CPAM. In rare cases of extensive involvement of nearly the entire lung, resection of multiple lobes or pneumonectomy may be necessary. There are several reports, however, detailing potentially lethal problems associated with pneumonectomy in newborns resulting from extreme mediastinal shift with vascular compression of the trachea and remaining bronchus (Szarnicki et al., 1978). Because of these risks, some groups advocate a non-anatomic resection to preserve as much pulmonary parenchyma as possible to allow postoperative compensatory growth and avoid post pneumonectomy complications (Mentzer et al., 1992). The newborn with a CPAM detected antenatally that subsequently regresses also needs careful postnatal evaluation. Often, subtle abnormalities will be evident on chest radiography but chest CT scanning may be necessary to detect residual CPAM tissue. Several authors have recommended that as long as these lesions are asymptomatic, they may be observed closely and managed without resection (Adzick et al., 1993; MacGillivray et al., 1993; Aziz et al., 2004; Hsich et al., 2005). The argument against this approach includes the reported cases of myxosarcoma, embryonal rhabdomyosarcoma, pleuropulmonary blastoma and bronchoalveolar carcinoma arising in CPAMs or indistinguishable from them.
While primary lung tumors are rare during the first two decades of life, 4% of those reported were associated with congenital cystic lesions of the lung, including CPAM (Benjamin and Cahill, 1991). While CPAM-associated malignancies often arise only after decades, the youngest patient reported with a malignancy was only 13 months of age (Ozcan et al., 2001). Because there is an anomalous connection to the tracheobronchial tree, infection is an additional potential complication (Stephanopoulos and Catsaros, 1963; Ueda et al., 1977; Weinberg et al., 1980; Krous and Sexauer, 1981; Weinblatt et al., 1982; Prichard et al., 1984; Sheffield et al., 1987; Hedlund et al., 1989; Domizio et al., 1990; Benjamin and Cahill, 1991; Morresi et al., 1995; Ribet et al., 1995; d’Agostino et al., 1997; Kaslovsky et al., 1997; Granata et al., 1998; de Perrot et al., 2001; Federici et al., 2001; Ozcan et al., 2001; Hasiotou et al., 2004; Galadzas et al., 2005; Poi et al., 2005). Some have argued that asymptomatic CPAMs should be followed expectantly and that the risks of surgery in infancy outweigh the potential benefits (Aziz et al., 2004). However, the continued presence of CPAM represents a lifelong risk of both infection and malignant transformation. In centers with significant experience in lung resection in infants, CPAMs can be safely resected with no mortality and virtually no morbidity. Our approach is to obtain a postnatal CT scan and use minimally invasive surgical approaches including muscle sparing thoracotomy, thorascopic lobectomy or non-anatomic resection when possible to retain normal lung tissue. An added benefit to resection over observation is that the remaining lung undergoes significant compensatory growth within months of the surgery. This does not occur if the CPAM is left in situ. The long-term outcome of infants with CPAM following resection is excellent. If residual CPAM is left behind or the mass is not resected, the child will remain at risk for infectious and potentially malignant complications. We recommend prophylaxis against RSV in infancy in those with significant associated pulmonary hypoplasia, pulmonary hypertension or chronic lung disease. Children who survived open fetal surgery for CPAMs associated with hydrops appear to be still doing well from 1 to 7 years postoperatively.
The initial evaluation of the patient with a suspected fetal CPAM should include a detailed ultrasound examination to confirm the diagnosis, including color flow Doppler studies to demonstrate or exclude systemic blood supply as seen in hybrid lesions or BPS. The size of the cysts within the lesion should be noted, as well as the size and location of the CPAM. Evidence of mediastinal shift and subtle signs of hydrops should be sought. The incidence of chromosomal anomalies in CPAM is uncertain. In the report by Adzick et al. (1998) among 134 prenatally diagnosed CPAMs at a tertiary-care center, there was only one fetus with a chromosomal abnormality (trisomy 21), for an incidence of only 0.7%. We recommend amniocentesis for karyotype analysis if fetal treatment is anticipated (D’Alton et al., 1993).
Often, a patient presents with a large CPAM and hydrops, in which case we proceed without a karyotype as long as there are no other sonographic abnormalities. Fetal echocardiography should be performed in all cases of suspected CPAM because of an increased incidence of associated cardiac anomalies, particularly truncus arteriosus and tetralogy of Fallot (Miller et al., 1980; Stocker et al., 1977). In addition, there is impaired cardiac function in large CPAMs that shift the mediastinum causing compression of the ventricles, elevated central filling pressures, altered ventricular inflow patterns and reversal of IVC flow with atrial contractions. This pattern of restrictive ventricular filling associated with flow reversals in the IVC with atrial contractions may be a harbinger of the development of hydrops. At a minimum, prenatal consultation should be obtained from a pediatric surgeon, a neonatologist and a pediatric cardiologist.
If there are associated life-threatening congenital anomalies, the family can be counseled and may choose not to continue the pregnancy. The development of the maternal “mirror syndrome” warrants immediate delivery. A fetus with an isolated CPAM but no hydrops should be followed closely by at least weekly serial sonography until plateau in CPAM growth is observed. Occasionally, these lesions will regress during gestation and CPAMs should be observed for signs of hydrops. All fetuses with CPAMs should be referred for delivery at a tertiary-care center, preferably with ECMO capability, where a planned delivery with appropriate resuscitation and surgery can be performed. There is usually no need for cesarean delivery of a baby with CPAM except for standard obstetrical indications and for cases which require EXIT-to-Resection.
The fetus with CPAM should be referred for delivery at a center with an intensive care nursery and appropriate staff available to resuscitate a newborn with potentially severe pulmonary hypoplasia. The newborn should be evaluated in the nursery to confirm the prenatal diagnosis and exclude other associated anomalies. The infant with type I or II CPAM may be at significant risk for air trapping in the CPAM, which may acutely worsen the respiratory status within hours of birth. In cases of unilateral CPAM, selective intubation of the contralateral bronchus may be a useful temporizing measure until resection of the CPAM can be accomplished. Pneumothorax is an additional concern in CPAM, especially in the type I or II lesions, and may require tube thoracostomy.
CPAM is usually confined to a single lobe. Rare cases have been reported of multilobar involvement of one lung or bilateral lesions (Rempen et al., 1987). Complete resection of the CPAM, usually by lobectomy, is the treatment of choice in CPAM. In cases of extensive involvement of nearly the entire lung, resection of multiple lobes or pneumonectomy may be necessary. There are several reports, however, detailing potentially lethal problems associated with pneumonectomy in newborns resulting from mediastinal shift with vascular compression of the trachea and remaining bronchus (Szarnicki et al., 1978). Because of these risks, some groups advocate a non-anatomic resection to preserve as much pulmonary parenchyma as possible to allow postoperative compensatory growth and avoid postpneumonectomy complications (Mentzer et al., 1992).
The newborn with a CPAM detected antenatally that subsequently regressed needs postnatal evaluation. Often, subtle abnormalities will be evident on chest radiography but chest CT scanning may be necessary to detect residual CPAM. Several authors have recommended that, as long as these lesions are asymptomatic, they be observed closely and managed without resection (Aziz et al., 2004; Hsich et al., 2005; Adzick et al., 1993; MacGillivray et al., 1993). The argument against this approach includes the reported cases of myxosarcoma, embryonal rhabdomyosarcoma, pleuropulmonary blastoma and bronchoalveolar carcinoma arising in CPAMs. While primary lung tumors are rare during the first two decades of life, 4% of those reported were associated with congenital cystic lesions of the lung, including CPAM (Benjamin and Cahill, 1991). While CPAM-associated malignancies often arise only after decades, the youngest patient reported with a malignancy was only 13 months of age (Ozcan et al., 2001). Because there is an anomalous connection to the tracheobronchial tree, infection is an additional complication for which these infants remain at risk.
Some have argued that asymptomatic CPAMs should only be followed and the risks of surgery in infancy outweighs the potential benefits (Aziz et al., 2004). However, CPAMs represent a life-long risk of both infection and malignant transformation. There are no means available to follow these patients and identify a problem before infection has occurred or malignant transformation has taken place. In centers with significant experience in lung resection in infants, CPAMs can be safely resected with no mortality and virtually no morbidity (Tsai et al., 2007, in press). Our approach is to obtain a postnatal CT scan and perform a muscle-sparing thoracotomy for lobectomy or non-anatomic resection whenever possible to retain normal lung tissue. An added benefit to resection over observation is that the remaining lung undergoes significant compensatory growth within months of the surgery. This does not occur if the CPAM is left in situ.
The long-term outcome of infants with CPAM following resection is excellent. If residual CPAM is left behind or the mass is not resected, the child will be at risk for complications. As noted above, these include air trapping with gradual enlargement over time, infection and malignancy arising within the CPAM. Also, as noted above, the infants usually have remarkable compensatory growth of the residual lung following resection, with continued alveolization for several years. Even in cases with severe pulmonary hypoplasia due to the CPAM, these children appear to have no limitations on their activities and are no more at risk for respiratory infections than other children. There is some data to suggest an increased predisposition to reactive airway disease in these children. We do recommend prophylaxis with synergies in infancy in children with significant pulmonary hypoplasia, pulmonary hypertension or chronic lung disease as they are not likely to tolerate RSV infection well. The children who survived open fetal surgery for CPAMs associated with hydrops appear to be still doing well from 1-7 years postoperatively.
CPAM has no known genetic defect responsible for its development and is thought to be an early developmental anomaly of uncertain cause. CPAM is not known to be specifically associated with chromosomal abnormalities, although one case of the 134 CPAMs reported by Adzick et al. (1998) had trisomy 21. No cases of recurrence of CPAM in a sibling or offspring have been reported.
A formal posterolateral thoracotomy in neonates and infants can have unintended morbidity related to decreased shoulder mobility, scoliosis and the development of chest wall deformities on long-term follow-up. As a consequence, the use of minimally invasive techniques, such as muscle sparing thoracotomy or thorascopic techniques, have become the preferred approaches in neonates and children.
The technique for a muscle sparing thoracotomy utilizes a 4 to 5cm transverse incision in the mid-axilla at about the level of the nipple. Skin and subcutaneous flaps are raised 6-10 cm circumferentially freeing the anterior surface of the latissimus dorsi and serratus anterior muscles. The anterior border of the latissimus dorsi is identified and the areolar tissue between it and the serratus anterior are divided pulling the latissimus posteriorly and the serratus anteriorly exposing the ribs. This level skin incision easily accommodates entry into the chest from as low as the 7th intercostal space to as high as the 3rd intra-costal space. The intercostal muscles and parietal pleura are incised as for a standard thoracotomy. Two Finochietto chest wall retractors are placed at 90 degrees to each other. One spreads the ribs while the second retracts the latissimus posteriorly and serratus anteriorly. Patience is required with the use of this technique as initial exposure will be limited until relaxation of the latissimus and serratus occurs with time. Especially in neonates, rib fractures can occur with overly aggressive retraction with the Finochiettos, which can be avoided by simply allowing time for muscular relaxation. The conduct of a lobectomy or segmental resection is then the same as for standard thoracotomy. The closure of a muscle sparing thoracotomy uses standard pericostal sutures to reapproximate the ribs. In addition to standard chest tube, if indicated, a small closed suction drain (TLS drain) is left above and below the raised muscle flaps to evacuate dead space and prevent accumulation of air or serous fluid. The TLS drain is placed to vacutainer suction every 4 to 8 hours and is usually ready for removal on post-operative day one along with the chest tube, if one was placed.
For the last decade, we have preferred to use minimally invasive techniques to perform lobectomies in all of these infants with congenital cystic lesions. The benefits of avoiding a formal thoracotomy and the morbidity associated with it greatly out way the disadvantages of the increased technical difficulty and operative time. In fact, with experience the operative times have equaled or are faster than with a standard thoracotomy.
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