Prognosis of infants with congenital pulmonary airway malformations after surgery: a short and mid-term evaluation.

OBJECTIVE: To investigate the postoperative pulmonary function, imaging descriptions and complications in infants with congenital pulmonary airway malformations (CPAM), and to examine the impact of different surgical resections on the prognosis of infants. METHODS: Data of 30 infants with CPAM who underwent surgery at the department of Pediatric Surgery, Guangzhou Women and Children's Medical Center from June 2021 to June 2022 were retrospectively collected and analyzed. The pulmonary function indexes of the infants during the first month and first year after surgery were analyzed to assess prognosis. Pulmonary function data from healthy individuals at similar age were collected as a control group. RESULTS: The post-operative short-term pulmonary function was recovered to a normal level in 26.7% cases of 30 CPAM infants, with a decrease in tidal volume (VT), ratio inspiratory time to expiratory time (TI/TE), time to peak tidal expiratory flow as a proportion of expiratory time (TPTEF/TE), volume to peak expiratory flow as a proportion of exhaled volume (VPEF/VE) and mean expiratory flow as a proportion of mean inspiratory flow (MEF/MIF) when compared to the control group (all P<0.01). One year after operation, 25 CPAM infants received pulmonary function tests and 52% of them had indexes at normal level. There was no statistically significant difference in results of pulmonary function test between infants who received lobectomy and those who received segmentectomy (P>0.05). The postoperative complication rate was 26.7%. CONCLUSION: Over half of CPAM infants have normalized lung function one year after operation and the choice of lobectomy and segmentectomy had no significant difference on prognosis of infants.

The Role of the miR-548au-3p/CA12 Axis in Tracheal Chondrogenesis in Congenital Pulmonary Airway Malformations.

Background: Literature has identified differentially expressed miRNAs in congenital pulmonary airway malformation (CPAM). However, the functional role of these miRNAs in CPAM remains unclear. Methods: We obtained diseased lung tissues as well as adjacent normal lung tissue from CPAM patients attending the centre. Hematoxylin and eosin (H&E) and Alcian blue staining were performed. Differentially expressed mRNA expression profile was CPAM tissue, and matched normal tissue specimens were examined by high-throughput RNA sequencing. CCK-8 assay, EdU staining, TUNEL staining, flow cytometry, and the Transwell assay were performed to investigate the effect of miR-548au-3p/CA12 axis on proliferation, apoptosis, and chondrogenic differentiation in rat tracheal chondrocytes. mRNA and protein expression levels were determined using reverse transcription-quantitative PCR and western blot analysis, respectively. The relationship between miR-548au-3p and CA12 was evaluated using the luciferase reporter assay. Results: The expression level of miR-548au-3p was significantly increased in diseased tissues compared with normal adjacent tissues from patients with CPAM. Our results indicate that miR-548au-3p functions as a positive regulator in rat tracheal chondrocyte proliferation and chondrogenic differentiation. At molecular level, miR-548au-3p promoted N-cadherin, MMP13, and ADAMTS4 expressions and reduced E-cadherin, aggrecan, and Col2A1 expressions. CA12 has been previously reported as a predicted target of miR-548au-3p, and here, we show that overexpression of CA12 in rat tracheal chondrocyte mimics the effects of inhibition of miR-548au-3p. On the other hand, CA12 knockdown reversed the effects of miR-548au-3p on cell proliferation, apoptosis, and chondrogenic differentiation. Conclusions: In conclusion, the miR-548au-3p/CA12 axis plays a role in the pathogenesis of CPAM and may lead to identification of new approaches for CPAM treatment.

Proteomic methods identified P75 as marker of poor prognosis in pleuropulmonary blastoma.

OBJECTIVES: To study the causes of the rapid progression of pleuropulmonary blastoma and to identify molecular markers related to its prognosis. MATERIALS AND METHODS: Three pairs of fresh frozen samples of pleuropulmonary blastoma tumors and adjacent normal tissues were analyzed for proteomics, focusing on the protein molecules with significantly increased expression in tumor tissues and related to the cell cycle and DNA replication. The top five protein molecules were selected and verified by immunohistochemistry. To analyze the correlation between the expression of verified protein molecules in pleuropulmonary blastoma and early recurrence/metastasis of pleuropulmonary blastoma. RESULTS: Compared with the adjacent normal tissues, 1759 proteins were upregulated and 967 proteins were downregulated in pleuropulmonary blastoma. The top five proteins related to the cell cycle and DNA replication were ORC2, P75, Skp2, MCM4 and PCNA. However, only P75, MCM4 and PCNA were upregulated in pleuropulmonary blastoma as determined by immunohistochemistry. Further analysis showed that the expression of P75 in the recurrence/metastasis group was significantly higher than that in the no recurrence/metastasis group, while the expression of MCM4 and PCNA was not significantly different between the recurrence/metastasis group and the no recurrence/metastasis group. CONCLUSIONS: MCM4, PCNA and P75 may all play an important role in the progression of pleuropulmonary blastoma. Among them, P75 is related to the prognosis and may be used as a marker to predict the prognosis of pleuropulmonary blastoma.

Treatment and prognosis of pleuropulmonary blastoma: A single-center report of 31 cases.

OBJECTIVES: Pleuropulmonary blastoma (PPB) is a very rare and highly aggressive neoplasm occurring in children, mostly under 6 years of age. We assessed the clinical characteristics, treatment modalities, treatment outcomes, and prognostic factors affecting survival in patients with PPB treated at our institution over a 10-year period to improve the prognosis. METHODS: From November 2008 to November 2019, 31 children (21 boys and 10 girls) with a median age of 30 months (ranging, 22 days to 54 months) were treated at our institution. Here we describe the patient characteristics, treatment modalities, and treatment outcomes. The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS). Log-rank test was performed for comparison between groups. RESULTS: Three children were lost to follow-up and two were dead due to postoperative complications. Of the 26 patients included in the follow-up, 16 PPB patients displayed tumor-free survival. The 5-year PFS and OS were 60.4% and 60.1% respectively. By stratified statistical analysis, the 5-year PFS and OS of type I PPB were 100%, while those of type III PPB were 43.7% and 43%, respectively. The 5-year PFS and OS of complete tumor resection were 76.5% and 75.6%, respectively, while those with tumor residue were 31.3%. The 5-year PFS and OS combined with chemotherapy were 62.2% and 61.6%, respectively, while those without chemotherapy were 0%. CONCLUSIONS: PPB is an aggressive neoplasm. The main factors related to the prognosis of PPB are pathological type, tumor resection degree, and postoperative adjuvant therapy.

circ0125803 facilitates tumor progression by sponging miR-197-5p and upregulating E2F1 in neuroblastoma.

BACKGROUND: Circular RNAs (circRNAs) are one type of RNAs with many different functions. circRNAs are very crucial in human malignancy progression. However, few studies have investigated the function and exact mechanism of circRNAs in neuroblastoma. In the current study, we investigated the biological function of circ0125803 in the proliferation and metastasis of neuroblastoma. METHODS: A high-throughput circRNA microarray sequencing was conducted to screen differentially expressed circRNAs and in neuroblastoma. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of circRNA and miRNA. RNA immunoprecipitation and dual luciferase reporter experiments were both conducted to investigate the molecular interaction mechanism of circ0125803 in neuroblastoma. RESULTS: We identified hsa_circ_0125803 (circ0125803) as an extremely upregulated circRNA in neuroblastoma samples. Knockdown of circ0125803 significantly decreased the growth rate and invasion rate in neuroblastoma. Our data demonstrated upregulation of circ0125803 promotes the neuroblastoma progression by blocking miR-197-5p and upregulating E2F1 expression. CONCLUSION: This study uncovered the biological function of the circ0125803-miR-197-5p-E2F1 axis in neuroblastoma metastasis and growth.

Analysis of miRNA Profiles and the Regulatory Network in Congenital Pulmonary Airway Malformations.

Background: Specific diagnostic markers for congenital pulmonary airway malformations (CPAMs) have not yet been discovered. This study intends to detect differentially expressed miRNAs in type I and type II CPAMs by using a miRNA chip and clarify the feasibility of miRNAs as different CPAM typing markers. Methods: Lung tissues of type I and type II CPAMs were collected and used to assess the differentially expressed miRNAs using a miRNA chip after evaluation using hematoxylin-eosin staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction and fluorescence in situ hybridization were used to verify the quality of the miRNA chip. The function and pathways of related differentially expressed miRNAs were analyzed by Gene Ontology Enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, respectively. Targets of miRNAs were predicted by targetscan7.1 and mirdbV6 and the network between miRNA and mRNA was established using Cystoscope software. Results: In total, 394/34 upregulated and 321/72 downregulated miRNAs were found in type I and type II CPAMs, respectively. GO and KEGG analysis showed that different pathways are involved in the regulation of CPAM, including platelet activation, Ras, MAPK, FoxO, and PI3K-Akt signaling pathways. miRNA-mRNA network analysis confirmed four major miRNAs in CPAM, including miR-4731-5p to complexin 2, miR-3150a-3p to vesicle amine transport 1, miR-32-5p to F-box and WD repeat domain containing 7, and miR-454-3p to SLAIN motif family member 1. Conclusion: In summary, we have identified four candidate miRNAs and pathways related to different pattern CPAMs, which provide a new perspective for CPAM research and treatment.

Clinical characteristics and therapeutic outcomes of mediastinal neuroblastoma with intraspinal extension: a retrospective study.

BACKGROUND: Mediastinal neuroblastoma (NB) can invade the spinal canal and result in spinal cord compression. Some patients go on to develop severe spinal deformities after decompression of the spinal cord. The optimal therapeutic strategy for mediastinal NB with intraspinal extension is still unclear. Our study is to assess the therapeutic strategies for such patients. METHODS: A total of 77 patients suffered mediastinal tumors with intraspinal extension between March 2015 and Aug 2019 were enrolled in the study. According to the primary therapy, NB were classified into 4 groups: chemotherapy, video-assisted thoracoscopic surgery (VATS)/thoracotomy, neurosurgical decompression, and a combined thoracic-neurosurgical approach. Clinical features, including patient demographics, neurologic recovery and survival rate, were assessed. RESULTS: Among the 77 patients suffered mediastinal tumors with intraspinal extension, neurological symptoms were present in 44 patients. Neurological deficits improved in 76.5% of patients who underwent neurosurgical intervention and 50% of the other patients (P=0.094). Compression manifestations of ≤4 weeks duration showed an improved outcome compared to a longer compression time, with complete recovery of neurological function in 60% of patients versus 28.6% for patients with a longer symptom duration (P=0.04). NB constituted 49.4% of the 77 patients. An overall survival rate of 90.0%±9.5% was achieved for patients in the combined thoracic-neurosurgical group, 59.5%±15.0% in the thoracotomy group, 40.0%±29.7% in laminectomy group, and 37.0%±20.2% in the chemotherapy group. Complete regression of the tumor was demonstrated in 80% of combined group, which was greater than that of patients in the other groups (P=0.001). CONCLUSIONS: Neurological recovery was correlated with the type of initial treatment and the duration of neurological symptoms. Mediastinal NB with intraspinal extension can be effectively managed with a combined neurosurgical and thoracic surgical approach.

The feasibility and safety of same-day surgery for diaphragmatic eventration by minithoracotomy in children.

PURPOSE: The diaphragmatic plication procedure by thoracoscopy has gradually become standard treatment for diaphragmatic eventration (DE). However, thoracoscopic diaphragmatic plication is difficult to manipulate and the surgical learning curve is long. This study aimed to demonstrate the feasibility and safety of same-day surgery for DE by minithoracotomy in children. METHODS: From December 2017 to December 2019, we included 22 patients who underwent diaphragmatic plication of DE in the Department of Pediatric Thoracic Surgery at the Guangzhou Women and Children's Medical Center. A total of 10 patients underwent diaphragmatic plication by minithoracotomy and 12 patients underwent thoracoscopic plication. The perioperative condition and postoperative follow-up were evaluated, respectively. RESULTS: The age, sex, and weight were no different in the minithoracotomy group versus the thoracoscopy group (P > 0.05). The intraoperative time, blood loss volume, and postoperative hospital stay of the minithoracotomy group were significantly less than that of the thoracoscopy group (31.10 ± 4.70 min vs. 72.08 ± 22.8 min; 1.20 ± 0.42 ml vs. 2.58 ± 1.67 ml; and 1.00 ± 0.00 days vs. 6.00 ± 2.95 days, respectively, all P < 0.05). The eventration levels in these two groups were significantly different in the perioperative and postoperative periods as detected by chest X-ray. No chest tubes were inserted and no recurrence of DE occurred in the thoracoscopy group through the postoperative follow-up of at least 6 months. CONCLUSION: Same-day surgery by minithoracotomy as a treatment for DE was feasible and safe with less operative time, less blood loss, and low recurrence. Same-day surgery for DE was attributed to a quick recovery. More prospective studies are necessary to further explore the consequences of same-day surgery for DE by minithoracotomy.

Surgical Treatment for Asymptomatic Congenital Pulmonary Airway Malformations in Children: Waiting or Not?

INTRODUCTION: Infection is undoubtedly the most important factor in influencing the timing and surgical strategy of congenital pulmonary airway malformation (CPAM) surgery. However, there have been no studies on the optimal timing of surgery for patients based on the probability of infection. The aim of this study was performed to explore the optimal timing of surgery of CPAM in children from the risk of infection. MATERIALS AND METHODS: The correlation of age distribution and pulmonary infection of 237 children diagnosed by pathology from January 2012 to January 2020 in Guangzhou Women and Children's Medical Center were analyzed retrospectively. We defined the cases with preoperative computed tomographic findings of infection, pathological findings of large number of neutrophils, tissue cells, and abscess formation as the infection group. RESULTS: The rate of infection in patients less than 2 years old was significantly lower than in patients over 2 years old (11.4% vs. 45.7%, p < 0.001). And the pulmonary lobectomy rate of patients with infection (29.0%) was significantly higher than in noninfected patients (17.2%) and whole patients (36.3%), p = 0.033. Patients with infection lose more blood during surgery (noninfected patients: 81.76 ± 13.14 mL, infected patients: 145.10 ± 25.39 mL, p = 0.027). The univariate analysis revealed that the infection rate of patients over 2 years old was 3.084 times that of patients ≤2 years old (odds ratio [OR]: 3.084, 95% confidence interval [CI]: 1.196-7.954; p = 0.020). The infection rate of CPAM types III and IV patients is lower than types I and II (OR: 0.531, 95% CI: 0.307-0.920; p = 0.024). CONCLUSION: In consideration of the high risk of infection, lower minimally invasive surgery rate, an increased rate of pulmonary lobectomy, and more blood loss in patients over 2 years old, our study also supports early surgical treatment. Therefore, we suggest that for asymptomatic patients with CPAM I and CPAM II, surgical treatment should be performed when they are less than 2 years old, providing more options for surgical strategies and monitoring of CPAM patients.

[Application of gastric tube esophagoplasty to complicated diseases of esophagus in children].

OBJECTIVE: To summarize the experience of applying gastric tube esophagoplasty for complicated diseases of esophagus in children and the short-middle-term efficacy. METHODS: A retrospective and observational case series study was performed. INCLUSION CRITERIA: (1) burn length of esophagus > 2 cm, multisegmental or extensive esophageal scar stenosis, and about 6 months after burn; (2) longitudinal diameter of esophageal tumor > 2 cm, or esophagus considered as impossible to reserve;(3) Severe esophageal fistula with diameter > 2 cm, or relapse again after ≥3 times of repair; (4) Tracheal cartilaginous esophageal heterotopia with a length of >2 cm or no end to end anastomosis after removal of the esophageal lesion. EXCLUSION CRITERIA: patients with severe cardiopulmonary insufficiency, or poor prognosis of gastric primary disease; the gastric volume did not allow long enough gastric tube; the parents did not accept the surgery. According to above criteria, 36 children with complicated diseases of esophagus who underwent gastric tube esophagoplasty at Department of Thoracic Surgery, Guangzhou Women and Children's Medical Center from March 2010 to June 2017 were enrolled into this study. Among 36 children, 27 were with corrosive strictures of esophagus, 5 with esophageal tumor, 3 with severe esophageal fistula, and 1 with tracheal cartilaginous esophageal heterotopia. Above-mentioned 27 cases with corrosive strictures of esophagus underwent gastric tube esophagoplasty via retrosternal route with preservation of the original esophagus. The other 9 cases underwent resection for esophageal lesion and gastric tube esophagoplasty via prevertebral route. The construction of gastric tube was as follows: the stomach was cut along the lesser curvature from pylorus to cardia and fundus of stomach with stapler, making the diameter of the gastric tube equal to pylorus. Operative time, intra-operative bleeding, time of mechanical ventilation, anastomotic leakage, anastomotic stricture were observed. The postoperative short-middle-term growth presentation of children was evaluated according to CDC 2000 children growth evaluation table(2 to 20 years). RESULTS: All the 36 children survived their operations successfully. Nine cases underwent esophagectomy for lesion esophagus and the other 27 cases received preservation of original esophagus. Average time of postoperative mechanical ventilation was 8 (4-20) hours. Three cases developed anastomotic leakage and were healed after one week. Eight cases developed anastomotic stricture and resumed normal diet after balloon expansion. The patients were followed up from 6 months to 7 years. Five cases were found to have esophageal cyst 4-8 months after the operation, and received resection. One children with infantile esophageal fibrosarcoma recurred 3 weeks after the operation and died 2 weeks later because the family abandoned the treatment. The quality of life of 35 cases was improved significantly. Short-middle-term body height and weight in 85.7%(30/35) children met basically the criteria of CDC 2000 children growth evaluation table. CONCLUSION: Gastric tube esophagoplasty can effectively treat the children with complicated esophagus diseases with good short-middle-term efficacy, and is a recommended esophageal replacement surgery.

Lack of associations between AURKA gene polymorphisms and neuroblastoma susceptibility in Chinese children.

Previous studies have demonstrated that polymorphisms in the AURKA gene are associated with various types of cancer. In neuroblastoma, AURKA protein product regulates N-myc protein levels and plays a critical role in tumorigenesis. To investigate the association between three AURKA polymorphisms (rs1047972 C>T, rs2273535 T>A, and rs8173 G>C) and neuroblastoma susceptibility in Chinese populations, we performed this two-center case-control study including 393 neuroblastoma cases and 812 controls. Two study populations were recruited from two different regions in China. No significant associations were identified amongst any of the three AURKA polymorphisms and the risk of neuroblastoma. Similar observations were found in the stratified analysis. In conclusion, our results indicate that none of the AURKA polymorphisms are associated with neuroblastoma susceptibility in two distinct Chinese populations. Further studies with larger sample sizes and different ethnicities are warranted to validate our results.

RSRC1 and CPZ gene polymorphisms with neuroblastoma susceptibility in Chinese children.

Two new neuroblastoma susceptibility loci at 3q25 (RSRC1 rs6441201 G > A) and 4p16 (CPZ rs3796725 T > C and rs3796727 A > G) were identified by a genome-wide association study (GWAS) involving Italians, African Americans and European Americans. In this case-control study with 393 neuroblastoma cases and 812 controls, we investigated the association between these three polymorphisms and neuroblastoma susceptibility in Chinese population. We found that participants harboring the RSRC1 rs6441201A allele were associated with an increased risk of neuroblastoma (AA vs. GG: adjusted OR = 1.55, 95% CI = 1.03-2.34, P = 0.036). No significant association between the CPZ polymorphisms (rs3796725 T > C and rs3796727A > G) and neuroblastoma susceptibility was observed. In conclusion, our results confirm that the RSRC1 rs6441201A allele is associated with neuroblastoma susceptibility in Chinese population.

[Preliminary study on gastric tube esophagoplasty for corrosive strictures of the esophagus in children].

OBJECTIVE: To study the clinical value of gastric tube esophagoplasty for complicated corrosive stricture of the esophagus in children. METHODS: A retrospective analysis was performed to study 7 patients with complicated corrosive stricture of the esophagus who were treated with gastric tube esophagoplasty via retrosternal route between March 2010 and October 2011. RESULTS: Three patients had a stricture longer than 2.5 cm, and 4 patients had more than one stricture. All the operations went well. The average time for mechanical ventilation postoperatively was 6 hours. No patients showed insufficient ventilation after withdraw of ventilator. There was 1 patient developed anastomotic leak which was healed a week later. One patient had anastomotic leak with pyloric obstruction, and the leak was healed 3 weeks after intraoperative placement of duodenal feeding tube and pyloric obstruction became patent 4 weeks later. There were 2 patients developed anastomotic stricture and they resumed normal diet after balloon dilatation. The average follow-up duration was 10.5 months. The quality of life was improved and no other complications were found. CONCLUSION: Gastric tube esophagoplasty is a effective alternative for complicated corrosive stricture of the esophagus and the short-term outcomes are favorable.