Congenital lung anomalies: can we postpone resection?

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1 Journal of Pediatric Surgery (2012) 47, Congenital lung anomalies: can we postpone resection? Nadja Colon a, Cameron Schlegel a, John Pietsch a, Dai H. Chung a,b, Gretchen Purcell Jackson a, a Department of Pediatric Surgery, Vanderbilt University Medical Center, Vanderbilt Children's Hospital, Nashville, TN 37232, USA b Department of Cancer Biology, Vanderbilt University Medical Center, Vanderbilt Children's Hospital, Nashville, TN 37232, USA Received 27 September 2011; accepted 6 October 2011 Key words: Congenital lung anomaly; CPAM; CCAM; Sequestration; Congenital lobar emphysema; Bronchogenic cyst Abstract Background/Purpose: The management of asymptomatic congenital lung lesions is controversial. It is unclear whether elective resection provides a significant benefit. We sought to determine whether early vs delayed resection of asymptomatic congenital lung malformations resulted in complications. Methods: Institutional billing records were queried for patients with lung malformations over a 10-year period. Medical records were reviewed for demographics, type of anomaly, symptoms, management, and procedural or disease-related complications. Results: Eighty-seven patients were identified. The diagnoses included congenital cystic adenomatoid malformation (41%), bronchogenic cyst (19.3%), sequestration (13.2%), and congenital lobar emphysema (12.0%). Fifty patients were observed for some period. Eleven became symptomatic, and 47 underwent resection at a mean age of 11 months. There was no difference in the type of resection, length of hospitalization, or complication rate between patients who underwent early vs delayed resection. There were no occurrences of malignancy or death. Conclusions: In our series, there was no difference in measurable outcomes between early and delayed resection of congenital lung lesions. These data provide some support for a management strategy that might include observation with delayed resection for asymptomatic patients. Published by Elsevier Inc. Corresponding author. Department of Pediatric Surgery, 2200 Children's Way, Suite 7100, Vanderbilt Children's Hospital, Nashville, TN 37232, USA. Tel.: ; fax: address: gretchen.jackson@vanderbilt.edu (G.P. Jackson). Congenital lung anomalies encompass a spectrum of rare but potentially life-threatening lung diseases that include congenital cystic adenomatoid malformations (CCAMs), bronchopulmonary sequestrations, bronchogenic cysts, and congenital lobar emphysema (CLE). The natural history of these lesions varies widely because patients may remain asymptomatic, experience regression, or have progressive cardiopulmonary symptoms. In the perinatal period, such lung lesions can result in pleural effusions, polyhydramnios, hydrops, and pulmonary hypoplasia with subsequent respiratory distress and airway obstruction. Postnatally, manifestations of congenital lung malformations can range from mild symptoms to significant complications that may include symptoms such as persistent cough, hemoptysis, pneumothorax, pneumonia, or airway compression with respiratory compromise. Because up to 30% may spontaneously regress in utero and many are asymptomatic at birth [1], congenital lung /$ see front matter. Published by Elsevier Inc. doi: /j.jpedsurg

2 88 N. Colon et al. anomalies are often diagnosed and followed prenatally without intervention. Fetal surgery is generally reserved for symptomatic fetuses with hydrops in an effort to minimize the risk of in utero demise. Although greater than 90% of live-born infants with CCAM may have radiographic evidence of parenchymal abnormalities [2], it is estimated that only 30% to 40% become symptomatic, thereby necessitating surgical resection [3]. More controversial, however, is the management of asymptomatic patients. It has been suggested that congenital lung anomalies serve as a source of recurrent infection and may even exhibit long-term malignant potential (ie, pleuropulmonary blastoma, rhabdomyosarcoma, and bronchioloalveolar carcinoma). Although not well documented, malignancy has been reported in up to 8.6% of patients with CCAM in 1 review series, irrespective of resection [4], whereas the likelihood of infection is closer to 10% in all patients with thoracic malformations based on published reports [5]. Although the optimal age for elective resection is debated, most pediatric surgeons advocate resection of all detected lesions. Few studies have evaluated a strategy of observation or delayed resection for congenital lung lesions. To date, there are no prospective randomized controlled trials evaluating short- or long-term outcomes with regard to observation or delayed resection in asymptomatic patients with congenital lung anomalies. A retrospective CCAM series of 48 patients reported that complications developed in 10% of asymptomatic patients [5]. Complications, such as recurrent pneumonias or infections, can theoretically lead to significant inflammatory changes that may make resection more difficult. As a result, a more extensive pulmonary resection has been reported in up to one third of patients with CCAM who present later in life [6]. In addition to decreased pulmonary function in older pediatric patients, lung resection in a young child is not without risk, as evidenced by the occurrence of complications such as bleeding, chylothorax, or empyema [7]. If resection whether early or delayed does not provide a clear benefit to asymptomatic patients, it might be reasonable to consider postponing elective resection until symptoms or complications develop. The purpose of this study was to review our institutional practices for congenital lung malformations and to determine whether observation or delayed resection of these lesions resulted in any untoward outcomes. 1. Methods After institutional review board approval, pediatric surgery billing records at our institution were queried for all patients who were diagnosed with or had resection of a congenital lung anomaly from January 2000 to December The search was conducted using specific International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes corresponding to the diagnoses and procedures in question. Pediatric surgeons at our institution performed all procedures. Demographics (ie, age, sex), diagnosis, symptoms, type of procedure, pathology, and length of stay (LOS) were collected from review of the operative report, anesthesia notes, daily progress notes, and discharge summaries. Findings from multiple imaging modalities were also extracted from the medical record to include the size and location of the lesion, in addition to the descriptors that characterized the type of lesion. From history and physical examination documents, clinic notes, and provider communications, other data that were evaluated included other anomalies, frequency of follow-up, hospital visits secondary to complications, malignancy occurrence, and mortality. Information regarding short- and long-term observational and postoperative complications was also collected and comprised instances of respiratory infection/pneumonia, respiratory failure, wound infection, pneumothorax, bleeding, or iatrogenic adverse outcomes (ie, intraoperative injury). Length of follow-up was measured as the time from which a patient was first evaluated at our institution for a congenital lung anomaly to the time that they were discharged from further followup. If a patient's medical record did not contain relevant data pertaining to a measurable end point, it was excluded from analysis for that end point only. For each end point, comparisons were made between 2 groups those who were observed before delayed resection and those who underwent immediate resection. The Student t test was performed to establish statistical significance, which was defined as P b Results A total of 93 patients were identified, but only 87 met inclusion criteria because 6 patients either had incomplete medical records or were lost to follow-up. There was no significant sex predominance, and the mean gestational age at birth was approximately 37.1 weeks (Table 1). Thirtyfive patients were diagnosed prenatally, and the average gestational age at diagnosis was 25.0 weeks (range, weeks). For all other patients, the diagnosis was made at an average age of 19.6 months (range, months) (Table 1). The original diagnosis was based on radiographic imaging, of which the most frequently used modalities were prenatal ultrasound (US) (41.2%), chest x-ray (CXR) (28.2%), and computed tomography (CT) (15.3%). A combination of imaging studies, such as US/CXR or CXR/CT, was used in 15.3% of cases for diagnostic confirmation. The initial diagnosis included CCAM (41%), bronchogenic cyst (19.3%), pulmonary sequestration (13.2%), and CLE (12.0%). However, hybrid lesions made up 6.0% of documented postresection cases, such that a total of 90 lesions were identified on resection. Preoperatively, malformations

3 Congenital lung anomalies: can we postpone resection 89 Table 1 Difference in presentation, management, and outcomes in patients who underwent delayed vs immediate operation Delayed resection Immediate resection P Total patients (%) 50 (57.5) 37 (42.5) Mean age at prenatal diagnosis (wk) Mean age at postnatal diagnosis (mo) Mean lesion size (cm) Length of observation (mo) 1-28 NA NA Imaging interval since previous study (mo) Mean, 3.7; median, 2 NA NA Mean, 4.1; median, 2 Mean, 7.2; median, 5 No. of symptomatic patients 11 (22.0%) 25 (67.6%) b.05 No. of regressions 3 (6.0%) 0 (0.0%).07 No. undergoing resection 47 (94.0%) 36 (89.7%) NA Age at resection (mo) Type of resection Thoracotomy, 36 Thoracotomy, VATS, 9 VATS, 5.26 Thoracoscopic conversion, 2 Thoracoscopy/laparoscopy, 1 NA Perioperative complications 6 (12.7%) 5 (13.9%).44 No. of malignancies 0 0 NA No. of deaths 0 0 NA NA indicates not applicable. were thought to involve the right hemithorax in 48 cases (53.3%) and left hemithorax in 32 cases (35.6%) as well as various other sites, such as the mediastinum or diaphragm. The average size of the lesion on imaging measured approximately cm for CCAM; cm for sequestration; cm for bronchogenic cyst; and cm for CLE. Lesions in patients who were observed were significantly smaller than those lesions in patients who were not (Table 1). Fifty-one patients (58.6%) were asymptomatic until they either underwent resection or were discharged from further follow-up. When symptomatic, the other 36 patients commonly presented with complaints related to recurrent respiratory infection/pneumonia (33.3%), shortness of breath (11.1%), and cough (11.1%) (Table 2). Sixteen patients were initially managed expectantly over a period of 1 to 28 months, whereas 34 asymptomatic patients were scheduled Table 2 Presenting symptoms in patients who underwent delayed vs immediate resection Immediate resection, symptomatic (n = 25) Delayed resection, symptomatic (n = 11) Respiratory distress, 12 Respiratory distress, 6 URI/pneumonia, 7 URI/pneumonia, 5 Wheezing, 5 Wheezing, 1 Tachypnea/SOB, 4 Cough, 1 Cough, 3 Tracheal obstruction, 2 Chest pain, 1 URI indicates upper respiratory infection; SOB, shortness of breath. for delayed elective resection. These patients were observed over a more definitive period of 3 to 6 months to allow for developmental maturity (Fig. 1). Serial imaging was performed to monitor regression or progression at intervals of approximately 3, 4, and 7 months on average after the previous imaging study. For those who were observed, follow-up imaging most frequently consisted of CT of the chest and/or CXR. By the time an observed patient underwent resection, an average of 2 CT scans had been obtained for surveillance. Three patients had documented regression of their malformations, which occurred over a mean of 8.3 weeks (range, 4-14 weeks). Because these regressions were incomplete, they underwent resection despite being asymptomatic. During the observation period of expectantly managed patients, 4 patients (25%) became symptomatic from recurrent respiratory infections, and resection was ultimately performed in 12 of the 16. Of those patients who were to undergo delayed elective resection, 7 (20.6%) became symptomatic (Fig. 1). In total, 83 patients (91.2%) underwent resection at an average of 18 months (range, 1 day to 13 years). The mean age of patients who required urgent operative intervention was approximately 1 month (27 days) because these neonates tended to present with severe respiratory distress that oftentimes necessitated intubation. Those who were observed were closer to 11 months of age at the time of operation. When the diagnosis was made incidentally or as part of the workup for symptoms, the mean age at resection was 44.4 months because these patients tended to be older at the time of presentation. Sixty-six procedures were performed with open (80.7%) and 14 thoracoscopic (16.9%) techniques, and 2 (2.4%) additional thoracoscopic procedures were converted to an

4 90 N. Colon et al. Fig. 1 Flow diagram representing management of patients with congenital lung anomalies. open approach. Thirty-six of the open procedures and 9 of the thoracoscopic procedures were performed in the observation group. Both conversions were performed in patients who underwent delayed elective resection, and the conversions were because of inadequate exposure attributed to the location and size of the lesion. There was no evidence on imaging that these lesions had enlarged over time, and as such, this finding had not been anticipated preoperatively. In the group that underwent immediate resection either after birth or once the diagnosis was made, 30 procedures were performed open, whereas 5 cases were performed thoracoscopically. There was no difference between the delayed vs the immediate resection group when it came to candidacy for video-assisted thoracoscopic surgery (VATS). For patients who underwent delayed operation with a thoracotomy, a lobectomy was performed in 25 patients (69.4%), segmentectomy/wedge in 7 (19.4%), bronchogenic cyst excision in 2 (5.6%), and sequestration excision in 2 (5.6%). In patients who underwent delayed operation with a thoracoscopic procedure, a lobectomy was performed in 5 patients (55.6%), segmentectomy/wedge resection in 1 (11.1%), and sequestration excision in 3 (33.3%). For the group that underwent immediate operation with a thoracotomy, a lobectomy was performed in 17 patients (56.7%), segmentectomy/wedge in 2 (6.7%), bronchogenic cyst excision in 9 (30.0%), and sequestration excision in 2 (6.7%). In patients who underwent immediate operation with a thoracoscopic procedure, a bronchogenic cyst excision was performed in 4 (80.0%), and a sequestration excision, in 1 (20.0%). Based on histologic confirmation, the preoperative diagnosis was accurate in 78.3% cases. Hybrid lesions (ie, containing 2 malformations) were missed on preoperative imaging in 5 patients, and malformations were incorrectly identified on imaging in 17 patients. For example, a CCAM diagnosed by prenatal US and confirmed by CT was found to be an intralobar sequestration and bronchogenic cyst at the time of resection. Similarly, a sequestration was unexpectedly encountered during the resection of a type II CCAM in 2 patients. Finally, 1 patient was diagnosed with CLE on prenatal US, which was suggested again on CT. However, a bronchoscopy revealed bronchial atresia instead. In 5 cases (6.0% of resected patients), pathology revealed the tissue was not a congenital malformation as diagnosed preoperatively but, instead, represented granulomatous inflammation, fibrosis, or lymphangiectasis. In all 5 of these patients, the diagnoses of CCAM (n = 4) or bronchogenic cyst (n = 1) were made on prenatal US, and a CT incorrectly suggested the presence of a malformation. The average postoperative LOS for all patients was 5.9 days (range, 1-48 days). There was no significant difference in the LOS for patients who underwent delayed vs immediate operation (4.0 vs 6.4 days). There was also no difference in the LOS based on whether the patients had an open or thoracoscopic procedure. Patients who underwent delayed operation with a thoracotomy or VATS had an LOS that averaged 4.4 and 2.8 days, respectively. This LOS is not significantly different when compared with their counterparts who underwent an immediate thoracotomy (6.9 days) or VATS (3.4 days). There were a total of 11 perioperative complications (13.2%). Of these, 6 (54.5%) occurred in the observation group that underwent a thoracotomy and included pneumothorax (n = 2) and lung abscess (n = 1). One patient developed an empyema (1.2%), which required a thoracoscopic decortication, whereas another had a chylothorax (1.2%) that required a repeat thoracotomy. The complications in the immediate operation group included pneumothorax (n = 2), Clostridium difficile colitis (n = 1), and arrhythmias (n = 1). There was not a significant difference in the complication rate between patients who underwent delayed (12.7%) vs immediate operation (13.9%). The length of follow-up ranged from 1 month to 3 years, averaging 13 months for patients who had a delayed operation and 2 months for those who underwent immediate resection. Follow-up for the 4 patients who did not undergo resection ranged from immediate discharge, which occurred with a family that declined operative intervention once the

5 Congenital lung anomalies: can we postpone resection diagnosis was made, to 6 months in a patient who was originally diagnosed with CLE but found to have bronchial atresia instead. The lack of long-term follow-up was attributed to the fact that once a patient underwent resection, he/she was discharged from further surgical follow-up if there were no ongoing issues. Although there was no incidence of malignancy or death, 2 patients with CLE who underwent delayed resection continued to experience recurrent pneumonias after resection. 3. Discussion For asymptomatic patients with congenital lung malformations, there is no consensus on the timing or necessity of resection. Without prospective studies on this topic, elective resection in infants who continue to be asymptomatic is recommended between 3 and 6 months of age. The primary concerns in delaying intervention are the development of complications and repeated radiation exposure from surveillance imaging. Some clinicians argue that there is an acceptable morbidity rate of approximately 9% associated with thoracotomy and resection, particularly when performed early to allow for compensatory growth of residual lung tissue [8-10]. It has been suggested that resection in symptomatic patients is technically more challenging because of chronic inflammatory changes [11], and therefore, it can be associated with higher morbidity. As minimally invasive techniques are increasingly adopted, thoracoscopic surgery may prove to be a safe and less morbid alternative to an open procedure [12,13]. Advocates further argue that early resection can prevent infectious complications and malignant transformation despite the fact that the reported incidence of cancerous progression is quite low and has yet proven to be causal or correlational. Although the incidence of infection in expectantly managed patients is unknown, 1 study found that 10% of infants with CCAM developed infections within 1 year of life, although the authors suggest that the true incidence is most likely higher owing to a short follow-up period. In this same study, 59% of expectantly managed patients had no complications; continued to be asymptomatic; and, at a median of 3 years follow-up, had not undergone resection [5]. Chetcuti and Crabbe [14] provided some evidence for conservative management by reviewing management of more than 100 congenital lung malformations at their institution, in which only 5% of patients developed a subsequent infection, whereas 85% of patients remained asymptomatic without surgical intervention. Another small retrospective study found no significant difference in the results of pulmonary function tests between children who underwent resection at greater than 2 or less than 2 years of age, suggesting that lobectomy during infancy does not provide a functional benefit compared with lobectomy later in childhood despite compensatory lung growth [15]. This, coupled with similar complication rates in asymptomatic patients with CCAM who are operated on when symptom free or after an infectious episode [5], may argue for longer observation periods before resection. Before the prenatal detection of these lesions, the delayed diagnosis of a congenital lung malformation would be made incidentally or when a patient presented in adolescence or adulthood with symptoms. In this subset of patients, detection of a malformation has not always required surgical resection, although it is performed more often than not. However, these patients, having presented later in life, have not seen poorer outcomes postoperatively when compared with their pediatric counterparts [16]. Because of the scarcity of reported cases, evidence-based guidelines have not been established. However, once infected, a malformation will likely continue to cause symptoms and, therefore, warrants surgical intervention [17]. Our data suggest that observing these lesions over a short time course did not result in untoward outcomes. The age at resection was still younger than 1 year in patients who underwent delayed operation, but they did not have serious complications from postponing resection outside the recommended window of 3 to 6 months of age. Moreover, many patients were operated on after becoming symptomatic and having a workup that incidentally revealed a congenital malformation. As a whole, these patients were older, having been diagnosed at a mean age of 44.4 months. These patients, who usually presented once they became symptomatic, justifiably underwent resection, which is what advocates of expectant management recommend. Although the true incidence of congenital lung malformations in the undiagnosed population is unknown, the patients who presented after the development of symptoms or who were incidentally diagnosed did not appear to have worsened short- or longterm outcomes in our study. They had similar complication rates and hospital LOS with no occurrence of malignancy or death. Our study is one of the larger published series of patients undergoing a delayed resection, and like most published series, it is limited by a short length of follow-up for most patients. We cannot draw conclusions about the long-term complications of resection or disease. Because 94% of the delayed resection group underwent operation regardless of symptoms, it is unknown how asymptomatic patients would have done if observation continued. The optimal procedures for following and managing these patients in the long term and into adulthood have yet to be established. However, observed patients are subjected to surveillance imaging, which amounted to 1 to 2 CXRs or CT scans over the course of observation in 3- to 7-month intervals. Nonetheless, observation did not preclude a minimally invasive approach, given that 19.1% of these patients successfully underwent a thoracoscopic resection, although 2 patients had to be converted to a thoracotomy because of inadequate exposure and size of the lesion, resulting in an 18.2% conversion rate. 91

6 92 N. Colon et al. Because only 4 patients did not undergo resection and were only followed up for a short period, it is difficult to draw conclusions about the long-term outcomes associated with a strategy of observation. The size of the lesion was significantly different between patients who were observed and those who were not, but this did not appear to dictate whether a patient subsequently underwent a thoracotomy or thoracoscopic resection. It should be noted that 3 lesions regressed to some degree during the observation period in asymptomatic patients. Although none of these lesions resolved completely, this finding confirms that these lesions are capable of involuting over time, which may allow for minimally invasive surgical resection or obviate the need for resection with longer periods of observation. Finally, resection has been advocated to make the correct diagnosis and prevent malignant transformation. Interestingly, prenatal US, CXR, and CT were accurate in only 78.3% of histologically confirmed diagnoses. These modalities incorrectly identified benign, nonanomalous malformations, thereby subjecting 5 patients to an unnecessary operation one of which developed a postoperative lung abscess. Nonetheless, observation allows for serial imaging, which may help clarify the diagnosis through comparison among previous studies over time. 4. Conclusion This study contributes to the small body of evidence supporting expectant management for asymptomatic congenital lung lesions. Our data did not reveal any serious complications during observation before resection of congenital lung lesions and suggest that further postponing or, perhaps, even foregoing surgical treatment in asymptomatic patients might be a reasonable option. The evidence base is significantly limited in follow-up for unresected lesions. Multicenter prospective trials, ideally with randomization and long-term follow-up, should be undertaken to determine the optimal management strategy. References [1] Martinez D. Prenatal ultrasound diagnosis of congenital lung lesions. Pediatr Pulmonol 2001(Suppl 23): [2] Stanton M, Njere I, Ade-Ajayiand N, et al. Systematic review and meta-analysis of the postnatal management of congenital cystic lung lesions. J Pediatr Surg 2009;44: [3] Wong A, Vieten D, Singhand S, et al. Long-term outcome of asymptomatic patients with congenital cystic adenomatoid malformation. Pediatr Surg Int 2009;25: [4] Hancock BJ, Di Lorenzo M, Youssefand S, et al. Childhood primary pulmonary neoplasms. J Pediatr Surg 1993;28: [5] Aziz D, Langer JC, Tuuhaand SE, et al. Perinatally diagnosed asymptomatic congenital cystic adenomatoid malformation: to resect or not? J Pediatr Surg 2004;39: [6] Makhija Z, Moir CR, Allenand MS, et al. Surgical management of congenital cystic lung malformations in older patients. Ann Thorac Surg 2011;91: [7] Nakajima C, Kijimoto C, Yokoyamaand Y, et al. Longitudinal followup of pulmonary function after lobectomy in childhood factors affecting lung growth. Pediatr Surg Int 1998;13: [8] Lo AY, Jones S. Lack of consensus among Canadian pediatric surgeons regarding the management of congenital cystic adenomatoid malformation of the lung. J Pediatr Surg 2008;43: [9] Laberge JM, Puligandla P, Flageole H. Asymptomatic congenital lung malformations. Semin Pediatr Surg 2005;14: [10] Ayed AK, Owayed A. Pulmonary resection in infants for congenital pulmonary malformation. Chest 2003;124: [11] Pelizzo G, Barbi E, Codrichand D, et al. Chronic inflammation in congenital cystic adenomatoid malformations. An underestimated risk factor? J Pediatr Surg 2009;44: [12] Rothenberg SS, Kuenzler KA, Middlesworthand W, et al. Thoracoscopic lobectomy in infants less than 10 kg with prenatally diagnosed cystic lung disease. J Laparoendosc Adv Surg Tech 2011;21: [13] Rahman N, Lakhoo K. Comparison between open and thoracoscopic resection of congenital lung lesions. J Pediatr Surg 2009;44: [14] Chetcuti PA, Crabbe DC. CAM lungs: the conservative approach. Arch Dis Child Fetal Neonatal Ed 2006;91: [15] Keijzer R, Chiu PP, Ratjenand F, et al. Pulmonary function after early vs late lobectomy during childhood: a preliminary study. J Pediatr Surg 2009;44: [16] Papagiannopoulos K, Hughes S, Nicholsonand AG, et al. Cystic lung lesions in the pediatric and adult population: surgical experience at the Brompton Hospital. Ann Thorac Surg 2002;73: [17] Zach MS, Eber E. Adult outcome of congenital lower respiratory tract malformations. Thorax 2001;56:65-72.