Early surgery before the onset of symptoms: a retrospective analysis of congenital cystic adenomatoid malformations of the lung

Introduction

Congenital cystic adenomatoid malformation of the lungs (CCAM), now commonly referred to as congenital pulmonary airway malformation (CPAM) (1), is characterized by the overgrowth of terminal bronchiolar structures and the formation of cystic and/or adenomatoid (gland-like) tissue within the lung parenchyma, which does not function in normal gas exchange. It is supplied by pulmonary circulation, has an incidence of 1:11,000 to 1:35,000 (2-4), and shows male predominance (5). CCAM is predominantly unilateral and involves only 1 lobe of the lung; bilateral CCAM is less common and has a worse prognosis (5,6). Recent advances in ultrasound technology and increased availability and accuracy of prenatal ultrasound screening have significantly increased the reported incidence and prenatal diagnosis of congenital cystic lung disease, and consequently, the need for diagnosis and treatment has increased as well (7-9). Early surgical intervention is recommended for symptomatic CCAM (10). For the optimal treatment of clinically asymptomatic CCAM patients, elective surgery is generally recommended, given the risks of recurrent infection and potential malignant transformation (11). Although early surgery may reduce or even prevent recurrent respiratory infections and malignant changes, concerns over anesthetic and perioperative risks in infants have led some surgeons to prefer delaying elective resection until the child is older, making the timing of elective surgery controversial (12). We reviewed all cases of CCAM treated at our study center in recent years, analyzed their morbidity characteristics, and evaluated the timing of surgery. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1847/rc).

Methods

Patient cohort

We collected clinical data of children with congenital cystic lung lesions who were diagnosed and underwent surgical treatment at the Department of Thoracic Surgery of Children’s Hospital of Fudan University between March 2016 and March 2024. Patients with a pathologically confirmed diagnosis of CCAM were screened for inclusion in the study. We included patients aged <18 years, those with available preoperative imaging data suggesting congenital cystic lung lesions, those having undergone open thoracic surgery/thoracoscopic surgery, and those with a clear diagnosis of CCAM by postoperative pathological examination. Cases with incomplete information were excluded.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective study was approved by the Ethics Review Board of the Children’s Hospital of Fudan University [No. (2025)34]. The need for patient consent was waived because of the retrospective nature of the study.

Collected variables

All surgical cases were initially screened. We specifically selected patients who underwent lobectomy and excluded those who underwent more limited resections (e.g., wedge resection or segmentectomy), thereby controlling for the extent of surgical resection as a potential confounding variable. The former were grouped according to the presence of preoperative clinical symptoms (divided into symptomatic and asymptomatic groups) and age at the time of surgery (divided into groups younger than 1 year old and older than 1 year old). The groups were compared for the differences in age at the time of surgery, growth and development, surgery duration, postoperative drain retention time, and length of postoperative hospital stay, among others.

Patients were classified as symptomatic if they met both of the following criteria. History of at least one episode of lower respiratory tract involvement attributable to the CCAM lesion, evidenced by one or more of the following: (I) recurrent pneumonia (≥2 radiologically confirmed episodes); (II) respiratory distress, dyspnea, or cyanosis not explained by other causes; (III) spontaneous pneumothorax; (IV) asthmatic spells or persistent wheezing requiring medical intervention. Corresponding objective findings at the time of or preceding the surgical intervention, including: (I) chest X-ray or CT scan findings consistent with acute or chronic pulmonary; (II) infection/inflammation (e.g., consolidation, air bronchograms, parenchymal opacities) in the region of the CCAM; (III) elevated systemic inflammatory markers (e.g., C-reactive protein, white blood cell count) during symptomatic episodes; (IV) documentation of supplemental oxygen requirement, non-invasive respiratory support, or hospital admission primarily for respiratory symptoms related to the CCAM. Patients who never exhibited any of the above clinical features before surgery were classified as asymptomatic. This includes patients with prenatal diagnosis and those with lesions discovered incidentally during imaging for unrelated conditions.

Statistical analysis

Data were statistically analyzed using SPSS. Qualitative data were described using numbers and percentages. Quantitative data were described using median, quartiles, and standard deviation. Two separate patient groups were compared: patients with CCAM with and without clinical signs at the time of surgery, and the main outcome parameters included body mass index (BMI), BMI-for-age Z-score (BAZ), age at the time of surgery, surgery duration, postoperative drain retention time, and length of postoperative hospital stay. Univariate statistical analyses were performed using the Chi-squared test and Mann-Whitney test. A significant difference was defined as a P value of <0.05.

Results

General information

We retrospectively enrolled 148 children with CCAM who were diagnosed and underwent surgical treatment in Children’s Hospital of Fudan University between March 2016 and March 2024. Among them, 97 (65.5%) were male and 51 (34.5%) were female, with a median age of 14.50 (8.00, 40.75) months. Their height, weight, and BMI were 79.00 (72.00, 100.00) cm, 10.9 (8.90, 15.23) kg, and 16.65 (15.36, 18.06) kg/m², respectively, with corresponding Z-scores of 0.76 (−0.09, 1.18), 0.76 (0.12, 1.70), and 0.71 (−0.24, 1.73). Eight children (5.4%) were born prematurely (Table 1).

Clinical features

Prenatal diagnosis was made in 87 cases (58.8%). In 66 cases (44.6%), the patient had presented with respiratory symptoms. Of the remaining asymptomatic children not diagnosed prenatally, all were identified incidentally through chest imaging performed for other reasons postnatally. Eleven cases (7.4%) had CCAM complicated by bronchopulmonary sequestration (BPS), of which all were intralobar and 20 cases (13.5%) were complicated with other malformations (Table 1).

Surgical treatment and postoperative care

The surgical approach was selected according to a standardized protocol. Preoperatively, eligibility for thoracoscopy was evaluated based on patient age, weight, and imaging characteristics of the lesion. Active infection necessitated delay of surgery until completion of antibiotic therapy and resolution of acute inflammation. Intraoperatively, a thoracoscopic port was initially established to visually assess the lesion, surrounding inflammation, and pleural adhesions. Conversion to thoracotomy was undertaken in cases where intraoperative findings—such as significant bleeding, unclear anatomy, or dense adhesions to critical structures—compromised safety or technical feasibility.

In this study, all children underwent lung tissue resection, 65 (43.9%) by video-assisted thoracoscopic surgery (VATS) and 83 (56.1%) by open thoracotomy, which included 4 cases that were intraoperatively converted to open thoracotomy. Among patients with single lung lobe involvement, 105 (70.9%) underwent lobectomy, 29 (19.6%) underwent wedge resection or segmentectomy, and 11 (7.4%) underwent a combined procedure involving ligation of the anomalous systemic artery and resection of the affected lobe. Besides, patients showing involvement of both lung lobes underwent lobectomy combined with segmental lung resection because of the extensive involvement of one of the diseased lobes and markedly less involvement of the other one.

After resecting the lung lesion, the lung was reinflated and assessed by the anesthesiologist, and if no obvious bleeding or air leakage was seen, closed chest drainage was performed. To drain the postoperative blood and fluid, a drainage tube was placed in the pleural cavity of the affected side, and then, the chest was closed in layers after reinflation of the lung. The surgery duration was 89.50 (65.25, 120.00) min. For further monitoring of their vital signs, the children were transferred to the cardiac intensive care unit, and most of them were transferred to the general ward on the first day postoperatively. Postoperative chest radiographs were obtained at scheduled follow-up visits to monitor for potential complications such as pneumothorax and pleural effusion. The resolution of these findings was a key determinant for the timing of chest drain removal. The postoperative chest drain retention time was 4.00 (3.00, 5.00) days. The length of postoperative hospital stay was 8.00 (7.00, 10.00) days (Table 1).

We compared the effects of thoracoscopic surgery (N=40) and open thoracic surgery (N=65) on surgery duration and short-term postoperative course and identified no significant difference in surgery duration (P=0.21), postoperative drain retention time (P=0.90), and the length of postoperative hospital stay (P=0.41) between the two surgical methods. In addition, based on the age of the patients, we compared the group younger than 1 year old with the group older than 1 year old and identified significant between-group differences in terms of the surgical approach (P<0.001) and surgery duration (P<0.001), with the former predominantly undergoing thoracoscopic surgery with a shorter duration and the latter predominantly undergoing open thoracic surgery (Table 2).

Pathological diagnosis

Serial paraffin sections were used for histopathological and immunofluorescence staining studies, and hematoxylin and eosin (H&E) staining was used for routine histological structural examination of the lungs. Pathological typing of CCAM was predominantly type 2 (Table 3).

Asymptomatic CCAM versus symptomatic CCAM

Children screened for undergoing lobectomy (N=105) were grouped into symptomatic and asymptomatic groups according to the presence or absence of preoperative clinical symptoms. Compared with children in the symptomatic group, those in the asymptomatic group were operated at a significantly younger age (median 11.00 vs. 34.00 months, P=0.005) and had a significantly higher BMI (median 16.89 vs. 15.64 kg/m², P=0.01) and BAZ (median 0.96 vs. 0.05, P=0.008) (Table 4). Additionally, overall comparison between the two groups revealed that the symptomatic group had significantly longer surgery duration (median 108.00 vs. 83.00 minutes, P=0.001).

According to the data records of this center, the mean operation duration was 98 minutes, the mean postoperative drain retention time was 5 days, and the mean length of postoperative hospital stay was 9 days. We compared the number of cases in each parameter that were lower or higher than their average values in the asymptomatic group and the symptomatic group. For those who underwent open lobectomy, surgery duration (P=0.046), postoperative drain retention time (P=0.003), and length of postoperative hospital stay (P=0.003) were more likely to be above the mean in the symptomatic group. For patients in the symptomatic group who underwent thoracoscopic surgery, the length of symptomatic surgery (P=0.01) was more likely to exceed the mean in these patients when compared with patients in the asymptomatic group; however, no significant difference was noted in the postoperative drain retention time (P=0.45) and length of postoperative hospital stay (P=0.65) (Table 5, Figure 1A).

Figure 1 Comparison of the short-term postoperative course between symptomatic and asymptomatic children with CCAM, stratified by surgical approach and age at surgery. (A) Comparison of postoperative short-term course between symptomatic and asymptomatic children with CCAM for different surgical approaches. (B) Comparison of postoperative short-term course between symptomatic and asymptomatic children of different ages with CCAM. n1 = CCAM with no clinical signs; n2 = CCAM with clinical signs. *, P<0.05. CCAM, congenital cystic adenomatoid malformation; VATS, video-assisted thoracic surgery.

Discussion

With the popularity of prenatal ultrasound, more and more cases of suspected CCAM are identified during the mother’s labor examination. Small lesions require close prenatal monitoring, do not require prenatal intervention, are usually asymptomatic at birth, and are amenable to elective surgical resection. Large lesions may result in mediastinal displacement with cardiac compression and impaired venous return, leading to fetal hydrops and affecting the development of the normal ipsilateral and contralateral lungs, resulting in pulmonary hypoplasia. These fetuses are at increased risk of fetal or neonatal death and may require prenatal intervention and/or consideration of lobectomy of the involved lungs (13).

Conversely, in cases where CCAM lesions were not identified by prenatal ultrasound, or when they were detected but did not necessitate prenatal intervention, the vast majority of patients remained asymptomatic at birth, though symptoms might emerge during their growth. The findings of this study showed that CCAM in most children was detected during prenatal ultrasound screening, and age at the time of surgery significantly differed between patients in whom CCAM was detected by prenatal testing and patients in whom it was detected without prenatal testing. Notably, patients in the asymptomatic group were significantly younger than those in the symptomatic group. Our analyses revealed that prenatal testing could identify children with CCAM at an early stage, thus allowing for early surgical intervention. Conversely, children with CCAM detected without prenatal testing were found to have respiratory symptoms at a later stage and were diagnosed as having CCAM after undergoing a chest CT examination, which led to a relatively higher age at the time of surgery.

Although there is a lack of global consensus on the optimal treatment of asymptomatic CCAM, early surgical intervention is generally recommended for symptomatic CCAM. Currently, when faced with a choice of whether to perform prophylactic surgery or closely observe and follow up the patient for the treatment of asymptomatic CCAM, most surgeons advocate early prophylactic surgery, particularly given the increased rate of recurrent lung infections and the risk of malignant transformation of CCAM tissue (14-16).

To clarify the optimal treatment options for patients with asymptomatic CCAM, many studies have compared the outcomes of elective resection in different age groups. In our study, the median BMI was significantly higher in the asymptomatic group than in the symptomatic group, and this difference remained significant even after adjusting for age by using the BAZ. As an age-standardized indicator of nutritional status, the significantly higher BAZ in asymptomatic children strongly suggests a relative growth advantage. This likely reflects the detrimental impact of recurrent lung infections on physical development. Therefore, early surgical resection of the diseased lobe may help prevent or minimize such growth impairment.

Besides recurrent lung infections, the potential for malignancy in CCAM, although rare, has been documented in the literature. Casagrande and Pederiva (17) integrated a systematic review of the literature describing lung tumors associated with CCAM in both pediatric and adult populations. A research shows that the congenital lung malformation (CLM) most frequently associated with tumors was found to be CCAM, particularly type I CCAM. In a report of primary lung tumors in children, 4% of the cases were associated with CCAM, including pleuropulmonary blastoma (PPB), adenocarcinoma, squamous cell carcinoma, rhabdomyosarcoma, and mesenchymal tumors. Another study of pulmonary rhabdomyosarcoma found that 45% of these occurred in pre-existing CCAM. Muntean et al. (18) analyzed 228 patients who underwent surgical resection for CLMs. Within this cohort, 6 cases of CCAM Type 1 were found to be associated with mucinous adenocarcinoma, representing 12% of that subtype. The study also pointed out that in 4 patients with malignant lesions, the CT imaging examination could detect the solid components in the lesions, indicating that imaging features may be helpful for risk stratification. It is not entirely clear whether pulmonary cystic lesions have a malignant tendency or whether these malformations are themselves PPBs. Therefore, prophylactic resection could be considered as an option under individualized assessment, particularly if potential malignant risk is taken into account.

Style et al. (19) assigned patients who underwent surgery before 4 months of age into the “early” group and those who underwent surgery after 4 months of age as the “late” group; they found no significant differences in time to surgery, postoperative pneumothorax rate, duration of chest drainage, and length of hospital stay between the two groups. Similarly, Duron et al. (12) defined “early intervention” as surgery within the first 4 months of life, “intermediate intervention” as surgery between 4 and 6 months, and “late intervention” as surgery between 6 and 12 months. Subsequently, they compared the prognosis of 63 patients who were assigned to these three groups and did not identify a significant correlation between postoperative course and age at the time of surgery. In the present study, we found that there were significant differences between the group under 1 year old and the group over 1 year old in terms of surgical methods and operation duration. The group under 1 year old tended to undergo thoracoscopic surgery and had shorter operation durations. In contrast, the operation duration for children with obvious symptoms in the group over 1 year old was higher than the average (Table 5, Figure 1B).

For those who underwent open lobectomy, surgery duration, postoperative drain retention time, and length of postoperative hospital stay were more likely to exceed the mean in the symptomatic group than in the asymptomatic group. Furthermore, for patients who underwent thoracoscopic surgery, the surgery duration was more likely to exceed the mean in the symptomatic group than in the asymptomatic group. Conforti et al. (20) reported that the durations of mechanical ventilation and pleural drainage were shorter in the asymptomatic group. We attributed these findings to the asymptomatic group having a shorter postoperative course and surgical treatment before the onset of symptoms possibly offering a better immediate outcome (16).

Current surgical techniques for the treatment of CCAM tend to be minimally invasive (21). Ceylan et al. (22) found no significant difference between VATS and open thoracic surgery in terms of perioperative complication rates, postoperative drain retention time, and the length of postoperative hospital stay; this coupled with the advantages of VATS in terms of postoperative pain control uphold it as the first choice for surgical treatment of patients with CCAM. Mayer et al. demonstrated that thoracoscopic resection of CLMs offers advantages over resection by thoracotomy in terms of postoperative recovery and musculoskeletal function (23). Vu et al. (24) compared thoracoscopic versus open surgery for the treatment of CCAM and found a significant correlation between the absence of preoperative symptoms and the success of the minimally invasive approach, suggesting that the possible reason for conversion to open surgery may be the difficulty in visualizing anatomy and separating adhesions because of the tissue adhesions caused by infections. Elhattab et al. (25) found that early intervention for CCAM before the onset of lung infection was associated with higher chances of successful thoracoscopic access, shorter operative time, and smoother postoperative course.

In the present study, we found that in patients who underwent thoracoscopic surgery, the surgery duration was more likely to exceed the mean duration in the symptomatic group than in the asymptomatic group. However, the presence or absence of symptoms did not affect the postoperative drain retention time or length of postoperative hospital stay. Furthermore, even patients who were symptomatic before the operation could have their chest drains removed within a shorter period of time, which reduced the risk of infection; this also allowed for their early discharge from the hospital, which provided them with a more comfortable recovery environment and alleviated their anxiety associated with prolonged hospital stay to some extent. Wei et al. (26) compared and analyzed the efficacy of thoracoscopic and da Vinci robotic-assisted surgery in the treatment of CCAM in pediatric patients and proposed that robotic-assisted thoracoscopic pneumonectomy is safe and feasible, with significant advantages in terms of short-term postoperative clinical outcomes.

This study has several limitations. First, its retrospective, single-center design and the limited sample size may affect the generalizability of the results. Second, it exclusively included patients who underwent surgical resection. The absence of a non-operatively managed cohort restricts our ability to comment on the natural history of CCAM or to compare outcomes between surgical and conservative management strategies. Finally, the lack of long-term follow-up data limits our evaluation of the impact of different surgical timings on long-term pulmonary function, growth, and quality of life in children. These constraints highlight the need for future prospective, multicenter studies with larger samples, multivariable adjustments, and long-term follow-up to better define the optimal timing and strategy for surgical intervention in CCAM.

Conclusions

We retrospectively analyzed patients with CCAM in our center and summarized the current characteristics of the pathogenesis and treatment of CCAM. The postoperative course of CCAM was shorter in the asymptomatic group, and surgical treatment before the onset of symptoms may offer a better short-term outcome. After the comparative analysis, the association of asymptomatic status with improved short-term recovery, combined with the known long-term risks of CCAM, supports the potential benefit of prophylactic lobectomy. This suggests that earlier intervention may be advantageous. Based on this, we suggest that prophylactic lobectomy should be performed as early as possible, performed with the informed consent of the parents. This approach aims to reduce risks and allow a longer period of compensation for the development of the residual lungs. Future prospective studies are needed to better define the long-term outcomes and optimal timing of intervention.

Acknowledgments

We thank Medjaden Inc. for scientific editing of this manuscript.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1847/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1847/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1847/prf

Funding: This work was supported by National Clinical Key Specialty Construction Project of China (No. 10000015Z155080000004).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1847/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Review Board of the Children’s Hospital of Fudan University [No. (2025)34]. The need for patient consent was waived because of the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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