Surgery in Congenital Lung Malformations: The Evolution From Thoracotomy to Minimally Invasive Surgery, 10-year Experience in a Single Center


 BackgroundCongenital lung malformation is an umbrella term and consist of various kind of parenchymal and mediastinal pathologies. Surgical intervention is often necessary for diagnosis and treatment for these pathologies. We aimed to review our experience in surgical treatment for congenital lung disease and present the role of minimally invasive surgery. Methods From January 2009 to May 2019, a total of 94 patients fitted the criteria for inclusion in this retrospective study. We investigated the clinical results obtained retrospectively.Results There were no significant differences between pathological subtypes in the postoperative length of hospital stay and drainage duration. There wasn't a significant difference between VATS and thoracotomy group in perioperative complicationsConclusions Congenital lung malformations consist of a heterogeneous group of diseases and video-assisted thoracoscopic surgery should be considered as the first choice in the surgical treatment of these patients.


Abstract Background
Congenital lung malformation is an umbrella term and consist of various kind of parenchymal and mediastinal pathologies. Surgical intervention is often necessary for diagnosis and treatment for these pathologies.
We aimed to review our experience in surgical treatment for congenital lung disease and present the role of minimally invasive surgery.

Methods
From January 2009 to May 2019, a total of 94 patients tted the criteria for inclusion in this retrospective study. We investigated the clinical results obtained retrospectively.

Results
There were no signi cant differences between pathological subtypes in the postoperative length of hospital stay and drainage duration. There wasn't a signi cant difference between VATS and thoracotomy group in perioperative complications

Conclusions
Congenital lung malformations consist of a heterogeneous group of diseases and video-assisted thoracoscopic surgery should be considered as the rst choice in the surgical treatment of these patients.

Background
Congenital malformation of the lung is an overarching term and consists of the bronchogenic cyst, pulmonary sequestration, congenital cystic adenoid malformation, congenital lobar emphysema, bronchial atresia, and enteric duplication cyst. It must be emphasized that there is no consensus regarding the nomenclature for these anomalies, but "congenital lung malformations" is the term that is most widely used in the literature. These malformations are usually diagnosed and managed in the newborn period, in infancy, or childhood. However, patients can also be entirely asymptomatic or present with nonspeci c symptoms like cough, chest pain, or dyspnea; therefore, diagnosis may be delayed until adult age [1][2][3].
In literature, there are several case series of congenital lung malformations in the neonatal/early childhood period, but there isn't enough study on the results of surgical treatment in older patients [4][5][6].

Patient Selection
This retrospective study was approved by the Institutional Review Board of the Dr Suat Seren Chest Diseases and Surgery Medical Practice and Research Center. We retrospectively reviewed medical records of 94 patients diagnosed with congenital lung malformation and surgically treated in our clinic between January 2009 and May 2019.
Thorax computed tomography (CT), respiratory function test and bronchoscopy were performed for all patients before surgery.
Patient demographic information, presenting symptoms, medical history, preoperative investigations, intraoperative ndings, histopathology, perioperative morbidity and mortality, length of hospitalization, and drainage time were collected.
Pathological subtypes (Bronchogenic cyst, sequestration, and others) and operation procedures (VATS vs. thoracotomy) were compared in terms of postoperative length of hospital stay, drainage time, and perioperative complications. The numeric rating scale (NRS) was used for the assessment of postoperative pain, and mean scores of VATS and thoracotomy groups were compared.
A perioperative complication was de ned as any complication occurring within 30 days after surgery.
Prolonged air leakage was de ned as air leak more than 7 days after surgery. Postoperative mortality was de ned as death occurring within 30 days post-surgery.

Surgical Management
All patients were placed in the lateral decubitus position under general anesthesia with selective one-lung ventilation.
VATS was performed through two or three incisions. Camera port was located at the 7th or the 8th intercostal space on the mid-axillary. The utility incision was located at the 4th of 5th intercostal space on the mid-axillary line. The third port was opened on the posterior axillary line if needed. These described locations were varied depending on lesion location and the surgeon's personal preference.
A 10-15 cm posterolateral skin incision was made, and serratus anterior muscle was spared for patients who underwent thoracotomy. The thoracic cavity was entered through the 4th, 5th, or 6th intercostal space.
The choice of the type of surgical procedure was the personal preference of the surgeon, but some patient-related factors were considered in this choice, also.
Thoracotomy was preferred in the presence of previous pulmonary infections, pleural thickening, cystic lesions larger than 5 cm, and the inability to tolerate single lung ventilation. However, with the increased experience, VATS for congenital lung malformation has increased relative to thoracotomy. Therefore, the presence of the above-mentioned conditions should not be considered strictly contraindicated.
Mediastinoscopy was also performed in one patient with the mediastinal cystic lesion, and total excision was achieved.
Lobectomy, pneumonectomy, wedge resection, or simple excision were performed, and intra-operative frozen section analysis was worked on the specimen if needed in case of suspicion of any malignancy.

Statistical Analysis
Data were analyzed using SPSS 22.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics for categorical variables are reported as frequency and percentage, and continuous variables are reported as mean value ± standard deviation (SD) or median (range) as appropriate.
Categoric variables were analyzed using Pearson's chi-square test or Fisher exact test. All statistical tests were two-sided, with p less than 0.05 de ned as achieving statistical signi cance.

Results
From January 2009 to May 2019, a total of 94 patients tted the criteria for inclusion in this retrospective study. There were 43 men and 51 women. The median age was 41, with a range of 16 to 78 years (Table 1).  The most common types of operation were cyst excision (n = 42, %44.6) and lobectomy (n = 30, %31.9).
The median postoperative length of stay and drainage duration were both ve days. Perioperative complications were seen in 13 (%13.8) patients. The most seen perioperative complication was prolonged air leakage (n = 11, %11.7). There was no intraoperative or perioperative death (Table 3). The most common type of lung malformation was a bronchogenic cyst (n = 71, %75.5).
There were no signi cant differences between pathological subtypes in the postoperative length of hospital stay and drainage duration. However, in cases of sequestration, the perioperative complication rate was signi cantly higher (p = 0.01) ( Table 4). The mean postoperative length of hospital stay and drainage duration was longer in the VATS group, but this data wasn't statistically signi cant (p = 0.706/p = 0.717). There wasn't a signi cant difference between VATS and thoracotomy group in perioperative complications ( Table 4).
The mean pain scores were lower in the VATS group in the rst three days of the postoperative period, and this difference was statistically signi cant (Table 4).
Although CTM is usually detected antenatally, the diagnosis may be missed until later in life, especially in asymptomatic cases.
The respiratory system begins the develop at about the 4th week of gestation from the ventral wall of the primitive foregut. This process continues until early childhood and consists of ve stages: Embryonic, pseudoglandular, canalicular, saccular, and alveolar. Most of the congenital lung malformations develop in the pseudoglandular phase, which is completed at the end of the 16th week [7,8].
Despite some similarities, congenital lung malformations are a heterogeneous group and cover a wide range of disorders. Therefore, we discussed the types of malformations in our case series under separate headings.

Bronchogenic cysts
A bronchogenic cyst is the most common congenital malformation of the mediastinum. They usually present as small, solitary cysts located in the mediastinum or pulmonary parenchyma. In imaging techniques, the density/intensity of the bronchogenic cysts may vary according to the cyst content, and they can mimic other mediastinal or parenchymal pathologies. Therefore, the bronchogenic cyst should be considered in the differential diagnosis of mediastinal and parenchymal lesions. Peripheral bronchogenic cysts are usually seen as multiloculated, thin-walled parenchymal lesions. They tend to have bronchial communication, and this situation can cause recurrent pneumonia, infection of the cyst, fever, sepsis, respiratory distress, or even severe hemoptysis. It was also reported that malignancy could develop on the wall of long-standing bronchogenic cysts. Therefore, the consensus in the treatment of this congenital malformation is complete surgical resection, even if the patient is asymptomatic [9][10][11][12][13].
In our experience, we detected two cases of malignant tumors arising from the bronchogenic cyst. One of them was mucoepidermoid carcinoma, and the other one was atypical carcinoid tumors of the lung. In both cases, bronchogenic cysts were located in pulmonary parenchyma and required anatomic lung resection. We also detected bronchogenic cyst incidentally in two cases of non-small cell lung cancer intraoperatively. In these two cases, the tumor was centrally located and accompanied by multiple mediastinal lymph nodes. The bronchogenic cyst was also located in the mediastinum and resected with other mediastinal lymph nodes. This is important for confusing the surgeon by creating the impression of a lymph node invading the bronchus. Therefore, in such cases, the result of the frozen section should be waited before beginning the anatomic resection.
We retrospectively analyzed 71 cases of a bronchogenic cyst in our series. Bronchogenic cysts were located in the mediastinum in 45 and pulmonary parenchyma in 26 out of 71 cases (Figure 1). VATS procedure was performed in 16 out of 71 patients. The intraoperative complication was seen in two cases. In the rst case, esophageal and bronchial laceration were seen together. In the other case, only esophagus perforation was seen. In these cases, the wall of the bronchogenic cyst strongly adhered to the bronchus and esophagus. Both lacerations occurred while dissection of the cyst wall from surrounding structures. These complications were detected intraoperatively and repaired without any problem.
Sometimes, bronchogenic cysts can reach large sizes and become perforated. This situation was observed in one of our patients (Figure 2). In such cases, surgery should be performed immediately.

Sequestration
Pulmonary sequestration is a rare malformation characterized by non-functional parenchymal mass, which receives arterial supply from aberrant systemic arteries. Pulmonary sequestration is divided into intralobar sequestration, which is located in normal pulmonary parenchyma without its pleural covering, and extralobar sequestration, which is separated from normal lung tissue by its pleural covering. Because of its distinctive arterial supply, this congenital anomaly may also be considered as a vascular malformation. Arterial supply of the pulmonary sequestration is usually from the descending thoracic or abdominal aorta, and venous drainage is usually toward the pulmonary veins ( Figure 3).
Patients can remain asymptomatic and be diagnosed incidentally or presented with dyspnea, cyanosis, recurrent pulmonary infection, and hemoptysis. Malignant transformation may also be seen in these patients. Therefore, surgical resection is the main treatment modality for pulmonary sequestrations, even for an asymptomatic patient [14][15][16].
In our series, we reviewed 15 patients with pulmonary sequestration. 11 of 14 patients had intralobar sequestration, and 4 had extralobar sequestration. VATS procedure was performed successfully in 6 out of 15 patients without any intraoperative complications. We also performed pneumonectomy in one case with synchronous extralobar pulmonary sequestration and centrally located lung cancer.
Preoperative evaluation of the arterial supply of pulmonary sequestration is essential for reducing the risk of intraoperative vascular injury [17,18]. Therefore, we used 3D multidetector CT angiography in all cases of pulmonary sequestration preoperatively. Thorax CT images of some of our cases are seen in Figure 4.
Compared to other congenital lung malformations, patients with sequestration had a higher rate of perioperative complications (%40.0), especially prolonged air leakage, and this data was statistically signi cant (p=0.01). This result can be explained by the need for anatomic lung resection instead of simple cystectomy in patients with pulmonary sequestration.

Congenital Cystic adenomatoid malformation (CCAM)
CCAM is a rare malformation characterized by cystic areas in the lung parenchyma and adenomatous overgrowth of the terminal bronchioles. Most of the cases are diagnosed prenatal or postnatally, and approximately 40% of the cases present with hydrops fetalis. In the presence of a small localized lesion, patients can remain asymptomatic for a long time and can be detected incidentally in later years, but most of the patients present with unresolving pulmonary in ltration, recurrent pneumonia, pneumothorax, or pleural effusion [19,20].
Surgical resection is the main treatment in patients with CCAM. The size and extent of the lesion determine the extent of surgical resection.
In our series, we surgically treated 2 cases of CCAM. One of these two patients had dyspnea, and the other had mild hemoptysis. Left upper and left lower lobectomy was needed to complete resection ( Figure  5).

Bronchial Atresia
Bronchial atresia is a rare congenital malformation characterized by focal interruption of lobar, segmental, or subsegmental bronchus.
In the embryological process, bronchial buds occur at the end of the 4th gestational week and continue to branch between 7th-16th weeks. Defect in vascularization can impact the branching of the bronchial buds and can cause interruption of a lobar or segmental bronchus. This results in mucus impaction and distension of the corresponding pulmonary parenchyma. Like many other malformations, bronchial atresia is most often diagnosed in the neonatal period or the young child. Surgical resection must be considered to make a diagnosis and prevent possible complications, even in asymptomatic patients [21,22].
In our series, bronchial atresia was detected in 2 cases. In these cases, atresia was containing left upper lobe anterior, and apicoposterior segment bronchus and pulmonary parenchyma distal to these bronchi were hyperin ated. Videothoracoscopic left upper lobe tri-segmentectomy was performed without any complication in both cases.

Enteric duplication cyst
Enteric duplication cyst is a rare congenital malformation originate from any part of the gastrointestinal tract. It was reported that approximately 20 percent of cases are located in the mediastinum, and most of them are detected in childhood. Symptoms depend on the size and location of the cyst, but dyspnea, stridor, cough, and chest pain may be present [23]. In our series, we detected 4 cases of mediastinal enteric duplication cysts, and surgical excision was performed.
Today VATS procedure is widely used in the diagnosis and treatment of different kinds of pulmonary, mediastinal, and pleural pathologies, and its indication is extending day by day.
In several studies, VATS was compared with thoracotomy, and it has been described as a safe and feasible technique for the treatment of congenital lung diseases (Table 5).
In addition to the described bene ts, VATS also allows excellent exposure of the entire hemithorax and allows the entire surgical team to follow every stage of the operation, but this procedure should be encouraged only for experienced surgeons.
With the increasing experience in our center, VATS has become the increasingly preferred method of surgical approach in patients with congenital lung malformation.
In our series, we performed a VATS procedure in 26 out of 94 patients. The intraoperative complication was seen in one case (esophagus laceration), and perioperative complication was seen in 5 cases (%19.2).
There weren't any statistically signi cant differences between VATS and thoracotomy groups in terms of perioperative complications, median postoperative length of hospital stays, and median drainage duration but mean postoperative pain score was signi cantly lower in the VATS group.
This study had some limitations. First, it is a retrospective study, and patient selection bias existed. Second, congenital lung malformations consist of a heterogeneous group of patients; therefore, it is di cult to make comprehensive inferences. Third, the criteria for selecting VATS were not de ned clearly, and we analyzed only a small number of patients at a single institution, a further large-scale prospective study will be necessary to investigate the e cacy and feasibility of VATS.

Conclusions
In conclusion, congenital lung malformation is an umbrella term and consist of various kind of parenchymal and mediastinal pathologies. To prevent future complications, surgery is always almost needed, even in asymptomatic patients.
In this study, there are no signi cant differences between VATS and thoracotomy groups in terms of intraoperative and perioperative complication rates, drainage, and hospitalization durations, but the advantage of VATS in postoperative pain control was also seen in our study. Because of possible and described bene ts of minimally invasive surgical techniques, VATS should be considered as the rst choice in the surgical treatment of patients with congenital lung malformations.

Declarations
Ethics approval and consent to participate This retrospective study was approved by the Institutional Review Board (Reg. no. 49109414-604.02).

Consent for publication
The authors declare that written consent was obtained from study participants.

Availability of data and materials
Not applicable.

Competing interests
The authors declare that they have no competing interests.