Management and Outcomes of Patients With High-Risk (Congenital Lung Malformation Volume Ratio≥ 1.6) Congenital Lung Malformations.

INTRODUCTION: Congenital lung malformations (CLMs) have a variable natural history. Larger lesions with CLM volume ratio (CVR) ≥ 1.6 are associated with hydrops and fetal mortality. The purpose of this study is to describe the management and outcomes of high-risk (CVR ≥ 1.6) CLM patients. METHODS: A retrospective cohort study was performed for all fetuses evaluated between May 2015 and May 2022. Demographics, prenatal imaging factors, prenatal and postnatal treatment, and outcomes were collected. Descriptive statistics were used to compare the cohorts. RESULTS: Of 149 fetal CLM patients referred to our fetal center, 21/149 (14%) had CVR ≥ 1.6. One CLM patient had intrauterine fetal demise, and 2 patients were lost to follow-up. Of the remaining 18 patients, 11/18 (67%) received maternal steroids. Seven out of 18 patients (39%) underwent resection at the time of delivery with 1/7 (14%) undergoing exutero intrapartum treatment (EXIT)-to-resection, 5/7 (71%) undergoing EXIT-to-exteriorization-to-resection, and 1/7 (14%) undergoing a coordinated delivery to resection; among those undergoing resection, there were 2 fatalities (28.5%). Seven out of 18 (39%) patients required urgent neonatal open lobectomies, and the remaining 4/18 (22%) patients underwent elective thoracoscopic lobectomies with no mortality. CONCLUSIONS: The natural history and outcomes of severe CLM patients remain highly variable. The EXIT-to-exteriorization-to-resection procedure may be a safe and effective approach for a subset of CLM patients with persistent symptoms of mass effect and severe mediastinal shift due to the observed decreased operative time requiring placental support observed in our study.

Congenital lung malformations: a nationwide survey on management aspects by the Italian Society of Pediatric Surgery.

INTRODUCTION: Over the years, congenital lung malformations (CLM) management remains a controversial topic in pediatric thoracic surgery. The Italian Society of Pediatric Surgery performed a national survey to study the current management variability among centers, trying to define national guidelines and a standardized approach of children with congenital lung malformations. METHODS: Following a National Society approval, an electronic survey including 35 items on post-natal management was designed, focusing on surgical, anesthesiology, radiology and pneumology aspects. The survey was conducted contacting all pediatric surgical units performing thoracic surgery. RESULTS: 39 pediatric surgery units (97.5%) participated in the study. 13 centers (33.3%) were classified as high-volume (Group A), while 26 centers (66.7%) were low volume (Group B). Variances in diagnostic imaging protocols were observed, with Group A performing fewer CT scans compared to Group B (p = 0.012). Surgical indications favored operative approaches for asymptomatic CLM and pulmonary sequestrations in both groups, while a wait-and-see approach was common for congenital lobar emphysema. Surgical timing for asymptomatic CLM differed significantly, with most high-volume centers operating on patients younger than 12 months (p = 0.02). Thoracoscopy was the preferred approach for asymptomatic CLM in most of centers, while postoperative long-term follow-up was not performed in most of the centers. CONCLUSION: Thoracoscopic approach seems uniform in asymptomatic CLM patients and variable in symptomatic children. Lack of uniformity in surgical timing and preoperative imaging assessment has been identified as key areas to establish a common national pattern of care for CLM.

Early resection of a rare congenital pulmonary airway malformation causing severe progressive respiratory distress in a preterm neonate: a case report and review of the literature.

BACKGROUND: Congenital pulmonary airway malformations (CPAMs) are a heterogenous collection of congenital lung malformations, often diagnosed prenatally. The Stocker Type III CPAM is a rare CPAM sub-type, and, when large, may be associated with hydrops. Furthermore, reports of CPAM management which may include surgical resection in extreme preterm infants are limited. CASE PRESENTATION: We report a case of a female neonate born at 28 weeks of gestation with severe respiratory distress and diffuse pulmonary opacification on the right concerning for a large congenital lung lesion. This lesion was not detected on routine antenatal imaging, and she did not have clinical findings of associated hydrops. Her respiratory status improved dramatically after surgical resection of a mass at 12 day of age. The mass was consistent pathologically with a Stocker Type III CPAM. Lung expansion showed subsequent improvement at 16 months of age. CONCLUSIONS: Our case describes a preterm neonate with severe respiratory distress that was found postnatally to have a large, unilateral congenital lung lesion despite a normal prenatal ultrasound. Additionally, this lesion required excision early in life due to severity of respiratory compromise. This case highlights that rare congenital lung lesions, like this rare sub-type of CPAM, should remain a diagnostic consideration in neonates with severe respiratory distress. Early lung resection for CPAM in preterm infants is not well described and the favorable outcomes of this case help expand perspectives on potential management strategies.

Short-term outcomes of thoracoscopic versus open lobectomy for congenital lung malformations.

PURPOSE: Thoracoscopic and open approaches for the management of congenital lung malformations (CLM) has been debated. The aim of this study is to compare 30-day outcomes for non-emergent lobectomies in children. METHODS: The National Surgical Quality Improvement Program-Pediatric database was queried for patients undergoing CLM resection from 2013 to 2020. Outcomes were compared by operative technique in an intention-to-treat model and then propensity matched. RESULTS: 2157 patients met inclusion criteria and underwent non-emergent pulmonary lobectomy for CLM. The intended operative approach was thoracoscopic in 57.7% of patients. Patients in the open group compared to the thoracoscopic were more likely to be born premature, have chronic lung disease, require preoperative oxygen support, and be ventilator dependent. After propensity matching, there was no statistically significant difference in 30-day mortality, unplanned readmission, and other complications between the thoracoscopic and open groups. Thoracoscopic approach was associated with a shorter length of stay. The proportion of cases approached via thoracoscopy increased over time from 48.8% in 2013 to 69.9% in 2020. CONCLUSIONS: This large multicenter retrospective matched analysis demonstrates thoracoscopic lobectomy in children has similar favorable 30-day outcomes and shorter length of stay for the non-emergent management of CLM, compared to open thoracotomy. LEVEL OF EVIDENCE: Level III.

Assessing the developing pharmacotherapeutic landscape in hepatitis B treatment: a spotlight on drugs in phase II clinical trials.

INTRODUCTION: Functional cure, defined as sustained HBsAg seroclearance, is associated with favorable outcomes in chronic hepatitis B (CHB). While nucleos(t)ide analogues (NAs) are effective in suppressing HBV replication, NAs are unable to induce functional cure at high rates. A range of novel HBV antivirals, aiming to induce functional cure, are currently under development. AREAS COVERED: This article covered novel hepatitis B virus (HBV) antivirals that have entered phase II trials. Virus-directing agents covered include entry inhibitors, transcription inhibitors, RNA silencers, core protein allosteric modulators, noncompetitive polymerase inhibitors, and viral protein export inhibitors. Immunomodulators covered include innate immune stimulators, T-cell modulators, therapeutic vaccines, and monoclonal antibodies. Upcoming developmental directions would also be discussed. EXPERT OPINION: Among novel HBV antivirals, RNA silencers, viral protein export inhibitors (with pegylated interferon), and entry inhibitors (with pegylated interferon) appear to be effective in suppressing HBsAg and may even induce functional cure. The other virus-targeting agents have variable effects on HBV DNA, HBsAg, HBeAg, and HBcrAg. Immunomodulators have modest effects on HBsAg but may have important roles in combination therapy. Upcoming trials will answer important questions on ideal dosing, long-term drug effects, and efficacy of combination regimens.

A single institution's experience with the management of peripheral bronchial atresia.

PURPOSE: Peripheral bronchial atresia is a pulmonary abnormality diagnosed on postnatal computed tomography after prenatal imaging reveals a congenital lung lesion. Debate regarding management of this abnormality prompted us to review our institution's practice patterns and outcomes. METHODS: All patients diagnosed with bronchial atresia were assessed from 6/2014 to 7/2020. Pediatric radiologists were surveyed to delineate computed tomography criteria used to diagnose peripheral bronchial atresia. Criteria were applied in an independent blinded review of postnatal imaging. Data for patients determined to have peripheral bronchial atresia and at least an initial pediatric surgical evaluation were analyzed. RESULTS: Twenty-eight patients with bronchial atresia received at least an initial pediatric surgical evaluation. Expectant management was planned for 22/28 (79%) patients. Two patients transitioned from an expectant management strategy to an operative strategy for recurrent respiratory infections; final pathology revealed bronchial atresia in both. Six patients were initially managed operatively; final pathology revealed bronchial atresia (n = 3) or congenital lobar overinflation (n = 3). CONCLUSIONS: Peripheral bronchial atresia can be safely managed expectantly. A change in symptoms is suspicious for alternate lung pathology, warranting further workup and consideration for resection. LEVEL OF EVIDENCE: Level IV.

Design, Synthesis, and Evaluation of a Set of Carboxylic Acid and Phosphate Prodrugs Derived from HBV Capsid Protein Allosteric Modulator NVR 3-778.

Hepatitis B virus (HBV) capsid protein (Cp) is necessary for viral replication and the maintenance of viral persistence, having become an attractive target of anti-HBV drugs. To improve the water solubility of HBV capsid protein allosteric modulator (CpAM) NVR 3-778, a series of novel carboxylic acid and phosphate prodrugs were designed and synthesized using a prodrug strategy. In vitro HBV replication assay showed that these prodrugs maintained favorable antiviral potency (EC50 = 0.28−0.42 µM), which was comparable to that of NVR 3-778 (EC50 = 0.38 µM). More importantly, the cytotoxicity of prodrug N8 (CC50 > 256 µM) was significantly reduced compared to NVR 3-778 (CC50 = 13.65 ± 0.21 µM). In addition, the water solubility of prodrug N6 was hundreds of times better than that of NVR 3-778 in three phosphate buffers with various pH levels (2.0, 7.0, 7.4). In addition, N6 demonstrated excellent plasma and blood stability in vitro and good pharmacokinetic properties in rats. Finally, the hemisuccinate prodrug N6 significantly improved the candidate drug NVR 3-778's water solubility and increased metabolic stability while maintaining its antiviral efficacy.

Prediction of postnatal outcome in fetuses with congenital lung malformation: 2-year follow-up study.

OBJECTIVES: To identify, in fetuses with a congenital lung malformation (CLM), prenatal predictors of the need for postnatal respiratory support and the need for surgery by calculating the CLM volume ratio (CVR), and to evaluate the concordance between the prenatal appearance and the postnatal type of CLM. METHODS: This was an analysis of prenatal, perinatal and postnatal data from fetuses diagnosed with a CLM at the Erasmus University Medical Center - Sophia Children's Hospital in Rotterdam, The Netherlands, between January 2007 and December 2016. For all included fetuses, CVR was measured retrospectively on stored ultrasound images obtained at 18 + 1 to 24 + 6 weeks (US1), 25 + 0 to 29 + 6 weeks (US2) and/or 30 + 0 to 35 + 6 weeks' gestation (US3). Postnatal diagnosis of CLM was based on computed tomography or histology. Primary outcomes were the need for respiratory support within 24 h and surgery within 2 years after birth. RESULTS: Of the 80 fetuses with a CLM included in this study, 14 (18%) required respiratory support on the first postnatal day, and 17 (21%) required surgery within 2 years. Only the CVR at US2 was predictive of the need for respiratory support, with a cut-off value of 0.39. Four of 16 (25%) fetuses which showed full regression of the CLM prenatally required respiratory support within 24 h after birth. The CVR at US1, US2 and US3 was predictive of surgery within 2 years. Overall, the prenatal appearance of the CLM showed low concordance with the postnatal type. Prenatally suspected microcystic congenital pulmonary airway malformation (CPAM) was shown on computed tomography after birth to be congenital lobar overinflation in 15/35 (43%) cases. Respiratory support within 24 h after birth and surgical resection within 28 days after birth were needed in all cases of macrocystic CPAM. CONCLUSIONS: CVR can predict the need for respiratory support within 24 h after birth and for surgery within 2 years. Regression of a CLM prenatally does not rule out respiratory problems after birth. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Anesthetic considerations in patients with cystic pulmonary adenomatoid malformations.

Congenital pulmonary adenomatoid malformation (CPAM) is a rare entity. The authors searched the US National Library of Medicine Database, EMBASE, Google Scholar, PubMed Central for anesthetic management in CPAM. The search was performed using the terms: congenital cystic adenomatoid malformation, congenital pulmonary adenomatoid malformation, CCAM, CPAM, anesthetic management. The prognosis of CPAM depends on timely diagnosis, presence of hydrops, degree of hypoplasia of remaining lung, and the size of the lesion. Symptomatic patients must be treated surgically and lobectomy is considered the gold standard. Anesthetic management of such cases is challenging as it involves thoracotomy or thoracoscopic lobectomy or cystectomy and can lead to sudden hemodynamic Collapse. Early extubation should be considered to avoid iatrogenic ventilator-induced bronchial stump dehiscence resulting from positive pressure ventilation.

Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference‡.

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase III trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive or negative chronic hepatitis, who are treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with an increase in bilirubin or international normalised ratio should prompt temporary or permanent cessation of an investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV coinfection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalisation of alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV 'functional cure', the primary goal is sustained HBsAg loss with undetectable HBV DNA after completion of treatment and the intermediate goal is sustained undetectable HBV DNA without HBsAg loss after stopping treatment.

Applications of Pediatric Body CT Angiography: What Radiologists Need to Know.

OBJECTIVE. Pediatric CT angiography (CTA) can be useful for assessing numerous congenital and acquired disorders. This article discusses common pediatric applications of thoracoabdominal CTA, including for congenital pulmonary airway malformation, sequestration, vascular rings, aortic coarctation, pulmonary embolism, nontraumatic hemorrhage, abdominal transplant evaluation, and several vascular disorders, and highlights key clinical and imaging features. CONCLUSION. With appropriate use, CTA can play a fundamental role in diagnostic and preprocedural assessment in a variety of pediatric conditions.

A case report of an unusual non-mucinous papillary variant of CPAM type 1 with KRAS mutations.

BACKGROUND: congenital pulmonary airway malformation (CPAM) is the most frequent congenital lung disorder. CPAM type 1 is the most common subtype, typically having a cystic radiological and histological appearance. Mucinous clusters in CPAM type 1 have been identified as premalignant precursors for mucinous adenocarcinoma. These mucinous adenocarcinomas and the mucinous clusters in CPAM commonly harbor a specific KRAS mutation. CASE PRESENTATION: we present a case of a 6-weeks-old girl with CPAM type 1 where evaluation after lobectomy revealed a highly unusual complex non-mucinous papillary architecture in all cystic parts, in which both mucinous clusters and non-mucinous papillary areas harbored the known KRAS mutation. CONCLUSIONS: we found that a KRAS mutation thought to be premalignant in mucinous clusters only, was also present in the other cyst lining epithelial cells of this unusual non-mucinous papillary variant of CPAM type 1, warranting clinical follow-up because of uncertain malignant potential.

Congenital pulmonary airway malformation associated with mosaic Klinefelter syndrome.

A 26-year-old female, G4 P2012 presented for an anatomy scan at 18 weeks. Multiple macrocysts were seen in the left fetal lung, which lead to a diagnosis of congenital pulmonary airway malformation (CPAM) type II. A fetal MRI examination performed at 24 weeks of gestation confirmed the diagnosis of CPAM type II. A genetic amniocentesis was done to rule out a fetal chromosomal abnormality and the fetus was found to have mosaic Klinefelter syndrome. Fetal CPAM is not usually associated with chromosomal abnormalities unless there are other fetal malformations present. This is the first known case where a fetus with CPAM and no other malformation was found to have mosaic Klinefelter syndrome. Therefore, we believe it is prudent to offer prenatal diagnostic testing whenever a fetus with CPAM is identified with ultrasound.

Predicting Pathology From Imaging in Children Undergoing Resection of Congenital Lung Lesions.

BACKGROUND: Prenatal magnetic resonance imaging (MRI) is increasingly obtained to define congenital lung lesions (CLL) for surgical management. Postnatal, preoperative computed tomography (CT) provides further clarity at the cost of radiation. Depending on the lesion identified, the indication for resection remains controversial. We investigated the differences in detail found on prenatal MRI and postnatal CT compared with final pathology to determine their utility in preoperative decision-making. MATERIALS AND METHODS: All children undergoing resection of CLLs at a single institution between July 2009 and February 2018 were retrospectively identified. Their imaging, operative, and pathology reports were compared. All imaging studies were examined by pediatric radiologists with experience in prenatal CLL diagnosis. RESULTS: Fifty-five patients underwent CLL resection during the study period with 31 undergoing prenatal MRI, 45 postnatal CT, and 22 both. Resection was performed before 6 mo of age in 62% of patients. In the cohort undergoing both imaging studies, pathologic CLL diagnosis correlated with prenatal MRI and CT in 82% and 100% of patients, respectively (P = 0.13). Eight patients had systemic feeding vessels, of which 38% were identified on MRI, and 88% on CT (P = 0.13). Both studies had a specificity of 100% for detecting systemic feeding vessels. CONCLUSIONS: For children where prenatal MRI detected a systemic feeding vessel, CT was redundant for preoperative planning but had greater sensitivity. Ultimately, the CLL type predicted from postnatal CT was not significantly different from that predicted by prenatal MRI; however, both imaging modalities had some level of discrepancy with pathology.

In prenatally diagnosed CPAM, does the affected lobe influence the timing of symptom onset?

PURPOSE: We investigated the relationship between the affected lobe and symptom onset in prenatally diagnosed congenital pulmonary airway malformation (CPAM). METHODS: 53 CPAM patients diagnosed prenatally were reviewed retrospectively by creating 2 groups according to symptom onset. Group Sneo: (symptomatic during the neonatal period; n = 13) and group S > neo: (symptomatic after the neonatal period; n = 40) were compared for type of CPAM, affected lobes, types of symptoms/infections, treatment, duration of follow-up, and histopathology. Requirement for surgery (Sx) was then used to create three subgroups: Sneo + Sx, S > neo + Sx, and Sx-. RESULTS: Some cases had multiple affected lobes. In Sneo, symptoms developed in 55.6%, 50.0%, 0%, 0%, and 36.8% of right upper lobes (RUL), right middle lobes (RML), right lower lobes (RLL), left upper lobes (LUL), and left lower lobes (LLL) diagnosed with CPAM, prenatally. In S > neo, symptoms developed in 0%, 0%, 6.3%, 55.6%, and 33.3% of RUL, RML, RLL, LUL, and LLL diagnosed with CPAM, prenatally. CONCLUSION: In prenatally diagnosed CPAM, RUL and RML lesions are more likely to become symptomatic in neonates, and LUL lesions in infants. Surgery is recommended before the onset of respiratory infections after 1 year of age.

Symptom development in originally asymptomatic CPAM diagnosed prenatally: a systematic review.

PURPOSE: For the approximately three quarters of patients with a prenatal diagnosis of congenital pulmonary airway malformation (CPAM) who are asymptomatic at birth, the chance of eventually developing symptoms is unknown. We sought to explore the natural history of asymptomatic CPAM. METHODS: We searched EMBASE, MEDLINE, and the first 50 results from Google Scholar. Studies describing the natural history of prenatally diagnosed, initially asymptomatic CPAM were included. For asymptomatic patients initially managed non-surgically, we tabulated the proportion who went on to develop symptoms as well as the median age at symptom development. RESULTS: We included data from 19 retrospective studies on 353 patients. Of the 128 patients managed expectantly, 31 (24.2%) developed symptoms requiring surgical intervention. The median age at symptom development was 7.5 months (range 15 days-5 years). CONCLUSION: The risk for developing respiratory symptoms exists with originally asymptomatic CPAM patients, but the exact risk is difficult to predict. Parents may be given the value of approximately 1 in 4 as an estimate of the proportion of asymptomatic CPAM patients who go on to develop symptoms, which will help them make an informed decision regarding the option of elective surgery.

Congenital pulmonary airway malformations: state-of-the-art review for pediatrician's use.

Congenital pulmonary airway malformations or CPAM are rare developmental lung malformations, leading to cystic and/or adenomatous pulmonary areas. Nowadays, CPAM are diagnosed prenatally, improving the prenatal and immediate postnatal care and ultimately the knowledge on CPAM pathophysiology. CPAM natural evolution can lead to infections or malignancies, whose exact prevalence is still difficult to assess. The aim of this "state-of-the-art" review is to cover the recently published literature on CPAM management whether the pulmonary lesion was detected during pregnancy or after birth, the current indications of surgery or surveillance and finally its potential evolution to pleuro-pulmonary blastoma. CONCLUSION: Surgery remains the cornerstone treatment of symptomatic lesions but the postnatal management of asymptomatic CPAM remains controversial. There are pros and cons of surgical resection, as increasing rate of infections over time renders the surgery more difficult after months or years of evolution, as well as risk of malignancy, though exact incidence is still unknown. What is known: • Congenital pulmonary airway malformations (CPAM) are rare developmental lung malformations mainly antenatally diagnosed. • While the neonatal management of symptomatic CPAM is clear and includes prompt surgery, controversies remain for asymptomatic CPAM due to risk of infections and malignancies. What is new: • Increased rate of infection over time renders the surgery more difficult after months or years of evolution and pushes for recommendation of early elective surgery. • New molecular or pathological pathways may help in the distinction of type 4 CPAM from type I pleuropulmonary blastoma.

Treatment of congenital pulmonary airway malformations: a systematic review from the APSA outcomes and evidence based practice committee.

PURPOSE: Variation in management characterizes treatment of infants with a congenital pulmonary airway malformation (CPAM). This review addresses six clinically applicable questions using available evidence to provide recommendations for the treatment of these patients. METHODS: Questions regarding the management of a pediatric patient with a CPAM were generated. English language articles published between 1960 and 2014 were compiled after searching Medline and OvidSP. The articles were divided by subject area and by the question asked, then reviewed and included if they specifically addressed the proposed question. RESULTS: 1040 articles were identified on initial search. After screening abstracts per eligibility criteria, 130 articles were used to answer the proposed questions. Based on the available literature, resection of an asymptomatic CPAM is controversial, and when performed is usually completed within the first six months of life. Lobectomy remains the standard resection method for CPAM, and can be performed thoracoscopically or via thoracotomy. There is no consensus regarding a monitoring protocol for observing asymptomatic lesions, although at least one chest computerized tomogram (CT) should be performed postnatally for lesion characterization. An antenatally identified CPAM can be evaluated with MRI if fetal intervention is being considered, but is not required for the fetus with a lesion not at risk for hydrops. Prenatal consultation should be offered for infants with CPAM and encouraged for those infants in whom characteristics indicate risk of hydrops. CONCLUSIONS: Very few articles provided definitive recommendations for care of the patient with a CPAM and none reported Level I or II evidence. Based on available information, CPAMs are usually resected early in life if at all. A prenatally diagnosed congenital lung lesion should be evaluated postnatally with CT, and prenatal counseling should be undertaken in patients at risk for hydrops.

Optimal age for elective surgery of asymptomatic congenital pulmonary airway malformation: a meta-analysis.

Controversy exists on the optimal age for elective resection of asymptomatic congenital pulmonary airway malformation. Current recommendations vary widely, highlighting the overall lack of consensus. A systematic search of Embase, MEDLINE, CINAL, and CENTRAL was conducted in January 2016. Identified citations were screening independently in duplicate and consensus was required for inclusion. Results were pooled using inverse variance fixed effects meta-analysis. Meta-analysis results indicate no statistically significant differences for complications within the 3-month and 6-month age comparison groups [odds ratio (OR) 4.20, 95% confidence interval (CI) 0.78-22.77, I 2 = 0%; OR 2.39, 95% CI 0.63-9.11, I 2 = 0%, respectively]. Older patients were significantly favoured for 3-month and 6-month age comparison groups for length of hospital stay [mean difference (MD) 4.13, 95% CI 2.31-5.96, I 2 = 0%; MD 3.38, 95% CI 0.44-6.31, I 2 = 0%, respectively]. Borderline statistical significance was observed for chest tube duration in patients ≥6 months of age (MD 1.06, 95% CI 0.02-2.09, I 2 = 0%). No mortalities were recorded. Surgical treatment appears to be safe at all ages, with no mortalities and similar rates of complications between age groups. The included evidence was not sufficient to make a conclusive recommendation on optimal age for elective resection.