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Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC). Chemotherapy resistance is the main cause of chemotherapy failure. Cullin7 (Cul7) is highly expressed in LUAD and is associated with poor prognosis. Moreover, Cul7 is abnormally overexpressed in docetaxel-resistant LUAD cells. Therefore, further exploration of the role and molecular mechanism of Cul7 in LUAD docetaxel resistance is necessary., Methods: We established docetaxel-resistant cell lines (A549DTX and H358DTX cell lines) by exposing cells to gradually increasing concentrations of docetaxel. Cell (A549, A549DTX, H358, and H358DTX cell lines) sensitivity to docetaxel was determined via a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymmethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. And then quantitative polymerase chain reaction (qPCR) and Western blotting were performed to measure the expression of Cul7 and Survivin in A549, A549DTX, H358, and H358DTX cell lines. Subsequently, we knocked down Cul7 in docetaxel-resistant cells and overexpressed Cul7 in parental cells via lentiviral transduction to further validate the correlation between Cul7 and docetaxel resistance, while exploring the molecular mechanism of docetaxel resistance it caused. Immunofluorescence and immunohistochemical (IHC) staining were also used to evaluate the expression and cellular localization of Cul7. To confirm the effect of Cul7 expression on cell apoptosis, we used flow cytometry to detect the apoptosis rate of A549 and A549DTX cells with the same drug concentration., Results: Cul7 was highly expressed in A549DTX and H358DTX cells. However, when Cul7 expression was knocked down in A549DTX and H358DTX cells, cell sensitivity to docetaxel was significantly increased. In addition, we found that Cul7 was coexpressed with Survivin . Silencing Survivin reversed the docetaxel insensitivity caused by Cul7 overexpression. High expression of Cul7 and Survivin in docetaxel-resistant LUAD cells inhibited the intrinsic apoptosis pathway and promoted cell proliferation. Therefore, the Cul7/Survivin axis may play a role in inducing LUAD docetaxel chemoresistance., Conclusions: Cul7 and Survivin were both highly expressed in docetaxel-resistant LUAD cells. Our results suggest that Cul7 may inhibit apoptosis and promote the proliferation of LUAD cells by increasing the Survivin protein level, which in turn contributes to docetaxel chemoresistance in LUAD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1110/coif). XL is from GZ Runsheng CytoMed Technology Co. Ltd. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background and Objective: The widespread use of chest computed tomography (CT) for lung cancer screening has led to increased detection of subsolid pulmonary nodules. The management of subsolid nodules (SSNs) is challenging since they are likely to grow slowly and a long-term follow-up is needed. In this review, we discuss the characteristics, natural history, genetic features, surveillance, and management of SSNs., Methods: PubMed and Google Scholar were searched to identify relevant articles published in English between January 1998 and December 2022 using the following keywords: "subsolid nodule", "ground-glass nodule (GGN)", and "part-solid nodule (PSN)"., Key Content and Findings: The differential diagnosis of SSNs includes transient inflammatory lesions, focal fibrosis, and premalignant or malignant lesions. Long-term CT surveillance follow-up is needed to manage SSNs that persist for >3 months. Although most SSNs have an indolent clinical course, PSNs may have a more aggressive clinical course than pure GGNs. The proportion of growth and the time to grow is higher and shorter in PSN than pure GGN. In lung adenocarcinoma manifesting as SSNs, EGFR mutations were the major driver mutations. Guidelines are available for the management of incidentally detected and screening-detected SSNs. The size, solidity, location, and number of SSNs are important factors in determining the need for surveillance and surgical resection, as well as the interval of follow-up. Positron emission tomography/CT and brain magnetic resonance imaging (MRI) are not recommended for the diagnosis of SSNs, especially for pure GGNs. Periodic CT surveillance and lung-sparing surgery are the main strategies for the management of persistent SSNs. Nonsurgical treatment options for persistent SSNs include stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA). For multifocal SSNs, the timing of repeated CT scans and the need for surgical treatment are decided based on the most dominant SSN(s)., Conclusions: The SSN is a heterogeneous disease and a personalized medicine approach is required in the future. Future studies of SSNs should focus on their natural history, optimal follow-up duration, genetic features, and surgical and nonsurgical treatments to improve the corresponding clinical management. All these efforts will lead to the personalized medicine approach for the SSNs., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5246/coif). SWU serves as an unpaid editorial board member of Annals of Translational Medicine from September 2022 to August 2024. The other author has no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: Pulmonary sequestration (PS) is a rare congenital lung malformation that can be incidentally diagnosed in adulthood. The natural course of PS in adults is scarcely known., Methods: In this retrospective cohort study, medical records and imaging results of adult patients diagnosed with PS between 1994 and 2019 were reviewed. Diagnoses of PS were confirmed by histopathological findings in resected cases, while non-resected cases were diagnosed based on the presence of anomalous systemic arterial supply and abnormal lung parenchyma on enhanced chest computed tomography (CT)., Results: Among 104 patients with PS, the median age at diagnosis was 40.5 years, and 69 (66.3%) patients were asymptomatic. Patients in the surgery group were significantly younger (38.6 vs. 45.3 years, respectively, P=0.016), were more likely to be symptomatic initially (51.6% vs. 28.6%, respectively, P=0.015), and had larger PS (90.0 vs. 66.3 mm, respectively, P<0.001) than the non-surgery group. Of the patients in the surgery group, 29.0% (18/62) experienced postoperative complications. In the surgically resected cases, infections were only detected in intralobar PS, not in extralobar PS. Among 25 subjects without initial symptoms in the non-surgery group, 24 (96.0%) remained asymptomatic at the last follow-up., Conclusions: Adults with PS tended to undergo resection if they were young, symptomatic, and had large PS (a median diameter of 90.0 mm). Almost all subjects who were initially asymptomatic and did not undergo surgery remained asymptomatic at the last follow-up. Therefore, considering the indolent course of PS, initially asymptomatic adults with PS could be followed up without surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-631/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background: We investigated the clinicoradiopathological features and prognosis according to genomic alterations in patients with surgically resected lung adenocarcinoma., Methods: Patients who underwent surgical resection for pathologic stage I, II, or IIIA lung adenocarcinoma between 2009 and 2016 and for whom results regarding EGFR mutation, ALK immunohistochemistry (IHC), and KRAS mutation were available were included. Clinicoradiopathological characteristics, genomic alterations, and disease-free survival were analyzed retrospectively., Results: Of 164 patients, 86 (52.4%) were female and 94 (57.3%) were never-smokers. The most common imaging patterns were part-solid lesion (67.7%) followed by solid (26.2%) and non-solid (6.1%) lesions. EGFR mutation, ALK IHC, and KRAS mutation were positive in 95 (57.9%), 9 (5.5%), and 11 (6.7%) patients, respectively. EGFR mutation positivity was associated with female sex, never-smoker, subsolid pattern on radiological examination, and acinar or papillary predominant histologic subtype. ALK IHC positivity was associated with longer maximal diameter, advanced stage, solid pattern on radiological examination, solid predominant histologic subtype, and distant metastasis during follow-up. KRAS mutation positivity was associated with male sex, smoker, solid pattern on radiological examination, and invasive mucinous adenocarcinoma on histologic analysis. In multivariable analysis, ALK IHC positivity and lymph node involvement were independently associated with recurrence. However, solidity was not an independent risk factor for recurrence., Conclusions: Genomic alterations are associated with clinicoradiopathologic features in patients with resected lung adenocarcinoma. Identifying genomic alterations could help to predict the prognosis of early-stage lung adenocarcinoma., Competing Interests: Conflicts of Interests: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1716). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: There are few reports comparing flexible and rigid bronchoscopy in adult foreign body (FB) aspiration. The aim of this retrospective study was to review the clinical characteristics, outcomes and factors associated with success in adult patients who underwent flexible or rigid bronchoscopy for airway FB removal., Methods: We retrospectively reviewed the records of 103 patients who underwent bronchoscopy to remove airway FB at Samsung Medical Center, South Korea from January 1999 to March 2017., Results: The median patient age was 64 years, and 70% were males. Among the 54 patients who underwent flexible bronchoscopy as first-line treatment, 43 (80%) patients had their FB successfully removed. Previous attempts at other hospitals was significantly associated with failed flexible bronchoscopy [9/11 (82%) vs. 3/43 (7%), P<0.001]. Delayed diagnosis (median 29 vs. 5 days, P=0.074) and peripherally located airway FB [9/12 (75%) vs. 23/48 (48%), P=0.115] were factors that trended towards flexible bronchoscopy failure. All of the 59 patients who underwent rigid bronchoscopy had their FB successfully removed. Rigid bronchoscopy was preferred to flexible bronchoscopy in patients with no comorbidities [38/59 (64%) vs. 18/44 (41%), P=0.018], previous attempts at other hospitals [34/59 (58%) vs. 4/44 (9%), P<0.001], delayed diagnosis (median 162 vs. 5 days, P<0.001), and hard FBs [48/62 (77%) vs. 21/49 (43%), P<0.001]., Conclusions: Our data suggest that previous failed attempts and delayed diagnosis are associated with flexible bronchoscopy failure. However, rigid bronchoscopy could be effective in removing an airway FB even in these cases. Further studies to identify factors to facilitate optimal patient selection will minimize failure rates and optimize resource utilization., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.