Congenital Pulmonary Airway Malformation in Children: Advantages of an Additional Trocar in the Lower Thorax for Pulmonary Lobectomy

Aim: To present the use of an additional trocar (AT) in the lower thorax during thoracoscopic pulmonary lobectomy (TPL) in children with congenital pulmonary airway malformation.Methods: For a lower lobe TPL (LL), an AT is inserted in the 10th intercostal space (IS) in the posterior axillary line after trocars for a 5-mm 30° scope, and the surgeon's left and right hands are inserted conventionally in the 6th, 4th, and 8th IS in the anterior axillary line, respectively. For an upper lobe TPL (UL), the AT is inserted in the 9th IS, and trocars are inserted in the 5th, 3rd, and 7th IS, respectively. By switching between trocars (6th↔8th for the scope, 4th↔6th for the left hand, and 8th↔10th for the right hand during LL and 5th↔7th, 3rd↔5th, and 7th↔9th during UL, respectively), vital anatomic landmarks (pulmonary veins, bronchi, and feeding arteries) can be viewed posteriorly. The value of AT was assessed from blood loss, operative time, duration of chest tube insertion, requirement for post-operative analgesia, and incidence of perioperative complications.Results: On comparing AT+ (n = 28) and AT– (n = 27), mean intraoperative blood loss (5.6 vs. 13.0 ml), operative time (3.9 vs. 5.1 h), and duration of chest tube insertion (2.2 vs. 3.4 days) were significantly decreased with AT (p < 0.05, respectively). Differences in post-operative analgesia were not significant. There were three complications requiring conversion to open/mini-thoracotomy: AT– (n = 2; bleeding), AT+: (n = 1; erroneous stapling).Conclusions: An AT and switching facilitated posterior dissection during TPL in children with congenital pulmonary airway malformation enhancing safety and efficiency.

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.

SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.