Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors.

PURPOSE: SMARCA4-deficient thoracic tumors are rapid aggressive malignancies, often diagnosed at an advanced and inoperable stage. The value of pulmonary resection for resectable SMARCA4-deficient thoracic tumors is largely unknown. METHODS: In this observational study, we included 45 patients who received surgery for stage I-III SMARCA4-deficient tumors. We compared the molecular, clinicopathological characteristics and survival between SMARCA4-dNSCLC and SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) patients. RESULTS: Thirty-four SMARCA4-dNSCLC and 11 SMARCA4-dUT patients were included in this study. Molecular profiles were available in 33 out of 45 patients. The most common mutated gene was TP53 (21, 64%), and followed by STK11 (9, 27%), KRAS (5, 15%), FGFR1 (4, 12%) and ROS1 (4, 12%). There were 3 patients that harbored ALK mutation including 1 EML4-ALK rearrangement. There were 2 patients that harbored EGFR rare site missense mutation. SMARCA4-dUT patients had significance worse TTP (HR = 4.35 95% CI 1.77-10.71, p = 0.001) and OS (HR = 4.27, 95% CI 1.12-16.35, p = 0.022) compared to SMARCA4-dNSCLC patients. SMARCA4-dUT histologic type, stage II/III, R1/2 resection and lymphovascular invasion were independent poor prognostic predictors for both TTP and OS. There were 8 patients who received immunotherapy, the objective response rate was 50%. The SMARCA4-dNSCLC patient with ALK rearrangement was treated with crizotinib as second-line therapy, and achieved stable disease for 9.7 months. CONCLUSION: Patients with SMARCA4-deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.

Minimally invasive sleeve lobectomy for centrally located lung cancer: A real-world study with propensity-score matching.

Background: The safety, feasibility, and prognosis of sleeve lobectomy by minimally invasive surgery (MIS) remain to be validated. The purpose of this study was to investigate outcomes in real-world patients receiving minimally invasive sleeve lobectomy in a balanced large cohort. Methods: Between January 2013 and December 2018, 578 consecutive patients undergoing sleeve resection at a high-volume center were retrospectively analyzed. Surgical and oncologic outcomes were compared between MIS and thoracotomy patients after propensity-score matching (PSM). Results: MIS sleeve lobectomy was increasingly used as a time-trend in real-world. Before PSM, the MIS group had smaller tumor size, more T2-stage cases, and more right upper lobe sleeve lobectomies compared to the Open group. After 1:4 PSM by patient demographics and tumoral characteristics, 100 cases of MIS and 338 cases of Open sleeve lobectomy were further analyzed. Although median operation time was longer in the MIS group than in the Open group (170.5 minutes vs.149.5 minutes, P < 0.001), patients in MIS group had significantly less estimated intraoperative blood loss (100 ml vs. 200 ml, P = 0.003), shorter drainage duration (5 days vs. 6 days, P = 0.027) and less amount of drainage (1280 ml vs. 1640 ml, P < 0.001) after surgery. Complete resection rate, combined angioplasty, number of dissected lymph nodes, post-operative length of stay, postoperative morbidity and mortality rate, and application of adjuvant therapy were similar between the two matched groups. Conversion to open thoracotomy was necessary in 13.6% patients, but with similar perioperative outcomes compared to Open cases except for longer operation time. More lower lobe sleeve lobectomies were accomplished via robot-assisted thoracoscopic surgery than via video-assisted thoracoscopic surgery (40.0% vs. 12.0%, P = 0.017) in MIS patients. Five-year overall survivals (MIS vs. Open: 72.7% vs. 64.4%, P = 0.156) and five-year progression-free survivals (MIS vs. Open: 49.2% vs. 50.5%, P = 0.605) were similar between the two matched groups. Conclusions: MIS sleeve lobectomy is associated with similar or even better perioperative results and oncologic outcomes to open thoracotomy. Conversion to thoracotomy does not compromise perioperative outcomes. Robot surgery may be preferable for more complex sleeve resections.

Synthesis of pyrazole peptidomimetics and their inhibition against A549 lung cancer cells.

A series of novel pyrazole peptidomimetics was synthesized from 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxylic acid and amino acid ester. Structures of the compounds were characterized by means of IR, (1)H NMR and mass spectroscopy. Compounds 5e and 5k suppress effectively the growth of A549 lung cancer cells. Preliminary research on the mechanism of action showed that the inhibition might perform through combination of apoptosis, autophagy and cell cycle arrest.

Preoperative Changes of Lung Nodule on Computed Tomography and Their Relationship With Pathological Outcomes.

Background: Whether changes of lung nodules on computed tomography could bring us helpful information related to their pathological outcomes remained unclear. Materials and Methods: This retrospective study was carried out among 1,185 cases of lung nodules in Shanghai Chest Hospital from January 2015 to April 2017, which did not shrink or disappear after preoperative follow-up over three months. Their imaging features, changes, and clinical characteristics were collected. A separate analysis was performed in nodules with or without growth in long-axis diameter after follow-up, searching significant changes related to nodule malignancy and the median interval of follow-up for reference. Further study was performed similarly in malignant nodules for discrimination of malignant grading. Results: Most nodules were stable (n = 885, 75%), whereas others grew (n = 300, 25%). For predicting nodule malignancy, increase in density (>10 Hounsfield units, median follow-up of 549 days) played an important role in growing group whereas it failed in stable group, and the increase in size was less significant in growing group. For discrimination of malignant grading, increase in density (>70 Hounsfield units, median follow-up of 366 days) showed its significance in stable group, and so did increase in size in growing group (maximum diameter growth >3.3 mm, median follow-up of 549 days, or average diameter growth >3.1 mm, median follow-up of 625 days). Conclusions: There were significant changes of lung nodules by follow-up on computed tomography, related to their pathological outcomes. The predictive power of increase in density or size varied in different situations, whereas all referred to a long-time preoperative follow-up.

Surgical Outcomes of Video-Assisted versus Open Pneumonectomy for Lung Cancer: A Real-World Study.

BACKGROUND: The safety, feasibility and potential benefits of Video-assisted thoracoscopic surgery (VATS) pneumonectomy remain to be investigated. METHODS: Patients receiving VATS or Open pneumonectomy during the study period were included to compare surgical outcomes. Propensity-score matched (PSM) analysis was performed to eliminate potential biases. RESULTS: From 2013 to 2020, 583 consecutive patients receiving either VATS (105, 18%) or Open (478, 82%) pneumonectomy were included. Conversion from VATS to open was found in 20 patients (19.0%). The conversion patients had similar rates of major complications and perioperative mortality compared with the Open group. After PSM, 203 patients were included. No significant differences were observed in major complications and perioperative mortality between the two groups. For patients with stage pT2 tumors, the major complication rate in the VATS group was significantly lower than in the Open group (7.6% vs. 20.6%, p = 0.042). Compared with left pneumonectomy, the incidence of bronchopleural fistula (BPF) was significantly higher in right pneumonectomy for both VATS (0 vs. 16.7%, p = 0.005) and Open (0.7% vs. 6.5%, p = 0.002) approaches. CONCLUSIONS: Perioperative results of VATS pneumonectomy are non-inferior to those of the Open approach. Conversion to open surgery does not compromise perioperative outcomes. Patients with lower pT stage tumors who need pneumonectomy may benefit from VATS.

Comprehensive analysis of prognostic predictors for patients with limited-stage small-cell lung cancer who underwent resection followed by adjuvant chemotherapy.

BACKGROUND: The prognosis of patients with limited-stage small-cell lung cancer (LS-SCLC) who undergo resection followed by adjuvant chemotherapy (ACT) is uncertain. Thus, we combined clinicopathological characteristics and next-generation sequencing (NGS) to answer this question. METHODS: In total, the data of 51 LS-SCLC patients who had undergone complete surgical resection and postoperative ACT were retrospectively collected. NGS examinations with a 68-gene panel were performed for each specimen. Patients' genetic status and potentially clinical correlations were statistically evaluated. Progression-free survival (PFS) and overall survival (OS) were plotted using Kaplan-Meier curves. The independent prognostic factors for the primary cohort were investigated using univariable and multivariable cox proportional hazard regression analyses. Subgroup analyses were also conducted based on retinoblastoma protein 1 (RB1) status. RESULTS: Combined SCLC (c-SCLC) had similar clinical and pathological characteristics to that of pure SCLC (p-SCLC). TP53 and RB1 were 2 major genetic mutations present in both p-SCLC and c-SCLC. c-SCLC had a unique genetic profile that was related to the PI3K/AKT/mTOR and WNT/ß-catenin signaling pathways. There was no prognostic difference between c-SCLC and p-SCLC. However, the pathological node (N) stage of lymphovascular invasion (LVI), which was related to PFS and age, corelated with OS. Neither pathological subtypes nor genetic mutations affected the survival outcomes. Notably, RB1 mutated c-SCLC resulted in poorer DFS compared to that of p-SCLC among LS-SCLC patients who underwent resection followed by ACT. CONCLUSIONS: Our examination of LS-SCLC patients who underwent resection followed by ACT showed that c-SCLC and p-SCLC had a clinical and prognostic similarity and a genetic peculiarity. Thus, it is essential that a new classification system be proposed for SCLC. Such a system is especially needed for LS-SCLC.

Risk stratification model for patients with stage I invasive lung adenocarcinoma based on clinical and pathological predictors.

BACKGROUND: The aim of this study was to propose a new kind of pathological classification and further establish a prognostic model for resected stage I invasive adenocarcinoma (IADC). METHODS: Clinicopathological data were collected from 2 hospitals. The new proposed pathological reclassification was defined according to certain subtype instead of a predominant one. Survival curves were plotted by Kaplan-Meier analysis. Cox regressions were analyzed for recurrence-free survival (RFS) and overall survival (OS), through which prognostic scores and stratification models were established. The comparison between risk models and the eighth edition of tumor, node, metastasis (TNM) classification was conducted through receiver operating characteristic curves (ROC), as identified by the area under the curve (AUC) and z test. RESULTS: In all, 1,196 patients were enrolled. At multivariable analysis, solid and micropapillary of the new pathological reclassification, along with stage IA3 and IB were independent predictors for poorer RFS. Stage IB and smoking status significantly indicated worse OS. After normalization and standardization of log-hazard ratio (HR), personalized scores were calculated and the risk stratifications with 3 risk groups were generated. Compared with TNM classification, the risk model of RFS showed advantage over early-recurrence prediction (1-year: 0.653 vs. 0.556, P=0.033; 3-year: 0.663 vs. 0.076, P=0.008). No marked difference was observed in long-term RFS or OS. CONCLUSIONS: Considering the harboring of certain patterns may be a new concept in adenocarcinoma classification. The risk stratification model based on this pathological classification and the eighth TNM classification showed remarkable superiority over TNM alone in predicting early recurrence of stage I adenocarcinoma. However, TNM classification remained valuable for long-term recurrence and survival prediction.

A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common and malignant cancer types. Abnormal cell proliferation, exemplified by cell cycle and cell division dysregulation, is one of the most prominent hallmarks of cancer and is responsible for recurrence, metastasis, and resistance to cancer therapy. However, LUAD-specific gene regulation and clinical significance remain obscure. Here, by using both tissues and cells from LUAD and normal lung samples, 434 increased and 828 decreased genes of biological significance were detected, including 127 cell cycle-associated genes (95 increased and 32 decreased), 66 cell division-associated genes (56 increased and 10 decreased), and 81 cell proliferation-associated genes (34 increased and 47 decreased). Among them, 12 increased genes (TPX2, CENPF, BUB1, PLK1, KIF2C, AURKB, CDKN3, BUB1B, HMGA2, CDK1, ASPM, and CKS1B) and 2 decreased genes (TACC1 and MYH10) were associated with all the three above processes. Importantly, 2 (CDKN3 and CKS1B) out of the 11 increased genes (except HMGA2) are previously uncharacterized ones in LUAD and can potentially be prognostic markers. Moreover, PLK1 could be a promising therapeutic target for LUAD. Besides, protein-protein interaction network analysis showed that CDK1 and CDC20 were the hub genes, which might play crucial roles in cell proliferation of LUAD. Furthermore, transcriptional regulatory network analysis suggested that the transcription factor E2F1 could be a key regulator in controlling cell proliferation of LUAD via expression modulation of most cell cycle-, cell division-, and cell proliferation-related DEGs. Finally, trichostatin A, hycanthone, vorinostat, and mebeverine were identified as four potential therapeutic agents for LUAD. This work revealed key regulators contributing to cell proliferation in human LUAD and identified four potential therapeutic agents for treatment strategy.

Marital status independently predicts non-small cell lung cancer survival: a propensity-adjusted SEER database analysis.

PURPOSE: Marital status has been demonstrated as an independent prognostic factor in many cancer types. The impact of marital status on non-small cell lung cancer (NSCLC) survival has not been assessed at the population level. Here, we used the surveillance, epidemiology and end results (SEER) database, a US national cancer registry, to address this issue. METHODS: All patients diagnosed with NSCLC from 2004 to 2009 were identified in the SEER database (version 8.3.2, updated at April 14, 2016). Those with incomplete clinicopathological information were excluded. The tumor, node, metastasis (TNM) staging was based on the criteria of the American Joint Committee on Cancer (AJCC) 6th edition. We used propensity-score matching analysis to balance baseline characteristics between the patients who were married and those who were not married. The impact of marital status on cancer-specific survival was analyzed with Cox proportional-hazards regression. RESULT: A total of 72, 984 NSCLC patients (41, 095 married patients, 56.3%) were enrolled in this study. After propensity-score matching, 25, 617 patients in the married group were 1:1 matched with patients in the unmarried group. Being unmarried was found to be associated with significantly decreased cancer-specific survival (hazard ratio (HR): 1.142, 95% CI: 1.119-1.166, p < 0.001). Among the unmarried group, patients who were single had worse cancer-specific survival (median survival 12 months, 95% CI: 11.37-12.63 months) than those who were divorced (median survival 15 months, 95% CI: 14.24-15.76 months, p < 0.001) or widowed (median survival 15 months, 95% CI: 14.25-15.76 months, p < 0.001). CONCLUSION: This study shows that marital status is an independent prognostic factor for cancer-specific survival in NSCLC patients. Patients who were married had better cancer-specific survival compared to the unmarried ones.

Analysis of the clinicopathological characteristics, genetic phenotypes, and prognostic of pure mucinous adenocarcinoma.

BACKGROUND: Primary pure mucinous adenocarcinoma of the lung (PMA) is a rare subtype. However, correlations between clinicopathological features and genetic phenotypes with survival have not been described comprehensively. METHODS: Pure mucinous adenocarcinoma patient information collected from the Surveillance, Epidemiology, and End Results (SEER) database, the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University (FDZSH), and the Cancer Genome Atlas (TCGA) were extracted, evaluated, and compared with other lung adenocarcinomas (LUAD) patient data. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the functional importance of underlying molecular changes. Overall survival (OS) was evaluated with the Kaplan-Meier method. Univariate and multivariate analysis through Cox proportional hazard regression identified risk factors that predicted OS, and the results were used to construct a nomogram to predict OS for PMA patients. RESULTS: Overall, 3622 patients, 41 patients, and 15 patients with PMA were identified from the SEER, FDZSH, and TCGA databases, respectively. There were 345 differentially expressed genes, 30 differentially mutated genes and 72 differentially methylated genes were identified between PMA and other LUAD samples. In the SEER database, PMA had a better prognosis compared to other LUAD. Compared with patients with other LUAD, patients with PMA exhibited unique clinicopathological features, including fewer grade III/IV tumors, less pleural invasion, more early-stage cancer, and more lower lobe carcinomas. Multivariate analyses showed that age, race, T stage, N stage, surgery, and chemotherapy were independent risk factors. The nomogram had a calibration index of 0.724. CONCLUSIONS: Our research identified unique clinicopathological characteristics and genetic phenotypes for PMA and other LUAD. The nomogram accurately predicted OS.

Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines.

BACKGROUND: Osimertinib (AZD9291), a third-generation EGFR-tyrosine kinase inhibitor, can effectively prolong survival in non-small cell lung cancer (NSCLC) patients with EGFR mutations, particularly T790M mutations; however, acquired resistance to AZD9291 is inevitable, thus exploration of the targets of resistance is urgent. METHODS: Considering the important role of circular RNAs (circRNAs) in cancers, we established AZD9291-resistant NSCLC cell lines (H1975/AZDR and HCC827/AZDR) and used microarray analysis to determine the circRNA expression profiles of the cells. The H1975/AZDR and HCC827/AZDR cell lines were induced by gradually increasing the drug concentration. CircRNA microarray expression profiles were obtained from H1975, HCC827, H1975/AZDR, and HCC827/AZDR cells and validated by quantitative reverse transcription PCR. Expression data were analyzed bioinformatically. RESULTS: The H1975/AZDR and HCC827/AZDR cell lines were successfully established. The half-maximal inhibitory concentration and the invasion ability of H1975/AZDR and HCC827/AZDR cells were significantly enhanced. The proliferation rates of H1975/AZDR and HCC827/AZDR were much lower than H1975 and HCC827. Microarray analysis identified 15 504 circRNAs differentially expressed in H1975, HCC827, H1975/AZDR, and HCC827/AZDR cells. Among them, 7966 were upregulated and 7538 were downregulated more than two-fold. We predicted the possible miRNAs of the top dysregulated circRNAs. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the most modulated circRNAs regulate several cancers and cancer-related pathways. CONCLUSION: Our results reveal that circRNAs may play a role in NSCLC AZD9291 resistance and might be a promising molecular target candidate for gene therapy.

Primary pulmonary meningioma mimicking lung metastatic tumor: a case report.

BACKGROUND: Primary pulmonary meningioma (PPM) is an extremely rare benign tumor. Previous reports indicated that CT features of PPM are single, solid, well-demarcated, homogeneous mass. In this study, we report a case of PPM with atypical CT features. CASE PRESENTATION: A 65-year-old female presents to clinic with 1-week acute upper respiratory tract infection. Her chest CT scan revealed a 25-29 mm, round-like, heterogeneous lobulated solitary pulmonary nodule in the right lower lobe. Based on the microscopic features and a wide range of immunohistochemical examinations including vimentine, progesterone receptor (PR), CD34 and S100, the mass was diagnosed as PPM after surgery. CONCLUSION: PPM is a rare disease, CT features of PPM could be heterogeneous and lobulated. Expression of vimentine, PR, CD34 and S100 helps to diagnosis of PPM.

Should minimally invasive lung adenocarcinoma be transferred from stage IA1 to stage 0 in future updates of the TNM staging system?

BACKGROUND: The 8th International Association Study of Lung Cancer (IASLC) TNM classification staging project for lung cancer has classified patients with adenocarcinoma in situ (AIS) into stage 0, while patients with a minimally invasive adenocarcinoma (MIA) were classified into stage IA1. However, MIA patients, similar to AIS patients, have an approximately a 100% 5-year survival. This study aimed to investigate if MIA could be transferred from stage IA to stage 0 in the next TNM staging system. METHODS: We retrospectively reviewed 1,524 consecutive patients with a pathologically confirmed AIS, MIA and an invasive adenocarcinoma (IADC) in stage IA1. Disease-free survival (DFS) and overall survival (OS) were analyzed to evaluate survival difference between these three groups. RESULTS: There were 412 AIS, 675 MIA and 437 IADC patients in stage IA1. No statistically significant differences for DFS and OS (P=0.109) were seen between the AIS and MIA groups. Patients of the IADC group had significantly worse DFS (P=0.003) but the OS rate (P=0.941) was insignificant when compared with the MIA patients. Similar survival results were seen when comparisons were made between the IADC and AIS/MIA groups. The IADC group had a worse DFS (P=0.001) rate but no OS (P=0.380) difference with the AIS/MIA groups. CONCLUSIONS: Patients with AIS and MIA had similar post-surgical survival rates. We propose that MIA may potentially be transferred from IA1 to stage 0 in the future.

Impact of Solid Minor Histologic Subtype in Postsurgical Prognosis of Stage I Lung Adenocarcinoma.

BACKGROUND: Few studies focus on the outcome and effect of a postsurgical treatment strategy for early stage patients with minor solid components pattern. This study investigated the prognosis and the adjuvant chemotherapy benefit among stage I invasive lung adenocarcinoma patients with minor solid components pattern according to the eighth TNM staging classification. METHODS: A total of 3,308 lung adenocarcinoma patients with mixed histologic components was divided into three groups: solid predominant, solid minor, and solid absent pattern. Disease-free survival and overall survival were analyzed to evaluate survival difference among patients in the different groups using the Kaplan-Meier approach and multivariable Cox models. RESULTS: Both solid predominant and solid minor groups showed significantly worse disease-free survival (p < 0.001) and overall survival (p < 0.001) compared with the solid absent group. There were no significant disease-free survival (hazard ratio [HR] 1.41, 95% confidence interval [CI]: 0.87 to 2.30, p = 0.161) or overall survival (HR 1.60, 95% CI: 0.83 to 3.09, p = 0.159) difference between the former two groups. For patients in stage IB, adjuvant chemotherapy improves disease-free survival (HR 0.33, 95% CI: 0.11 to 1.02, p = 0.044) but not overall survival (HR 0.61, 95% CI: 0.21 to 1.77, p = 0.360) in the solid predominant group. No adjuvant chemotherapy benefits for disease-free survival (HR 1.04, 95% CI: 0.49 to 2.22; p = 0.922) and overall survival (HR 0.49, 95% CI: 0.13 to 1.90; p = 0.291) were seen for the solid minor group. CONCLUSIONS: Solid minor components predict a significantly worse prognosis compared with the solid absent pattern. However, adjuvant chemotherapy may be unhelpful to improve outcomes for stage IB patients with solid minor components after surgery.

Prognosis of limited resection versus lobectomy in elderly patients with invasive lung adenocarcinoma with tumor size less than or equal to 2 cm.

BACKGROUND: This study aimed to evaluate the prognostic difference between limited resection and lobectomy among elderly patients with small size lung adenocarcinoma. METHODS: A total of 666 patients >65 years old with stage I lung adenocarcinoma and tumor size ≤2 cm were included. The patient survival was evaluated by disease-free survival (DFS) and overall survival (OS). Results: No DFS or OS advantage was found between the lobectomy and wedge resection groups when tumor sizes were ≤1 cm (DFS, P=0.112; OS, P=0.294). The wedge resection group had a significantly worse OS (P=0.041) than that in the lobectomy group when tumor sizes were >1 cm and ≤2 cm. CONCLUSIONS: We conclude that wedge resection may be a reasonable surgical choice for elderly patients with tumor sizes ≤1 cm.

Genetic analyses of differences between solid and nonsolid predominant lung adenocarcinomas.

BACKGROUND: Solid predominant lung adenocarcinomas (LUAD) have distinct histopathological and clinical characteristics compared with nonsolid subtypes. A comprehensive comparison of altered genes found in solid and nonsolid subtypes has not previously been performed. In this study, we analyzed differences in gene expression, genetic mutations, and DNA methylation to better understand the risk factors for these two subtypes of LUAD. METHODS: Differentially expressed genes (DEGs) and differentially mutated genes (DMGs) were analyzed from RNA-seq data downloaded from The Cancer Genome Atlas (TCGA) and Broad Institute database. To understand the functional significance of molecular changes, we examined the DEGs and DMGs with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. RESULTS: A total of 184 patients in the TCGA cohort and 140 patients in the Broad Institute cohort were included in this study. We identified 75 DEGs, of which 15 were upregulated and 56 downregulated in the solid group relative to the nonsolid group. The DEGs were mainly involved in the regulation of water and fluid transport. We discovered 38 significantly differentially expressed genes that overlapped in the two groups. The DMGs were mainly enriched for pathways involved in cell-cell adhesion, cell adhesion, biological adhesion, and hemophilic cell adhesion. We additionally discovered nine significantly methylated genes between solid and nonsolid LUAD. CONCLUSIONS: Our study identified distinct DEGs, DMGs, and methylation genes for solid and nonsolid LUAD subtypes. These findings improve our understanding of the different carcinogenesis mechanisms in LUAD and will help to develop new therapeutic strategies.

Comprehensive study of prognostic risk factors of patients underwent pneumonectomy.

Introduction: To investigate postoperative complications and the prognostic risk factors of patients underwent pneumonectomy. Methods: Four hundred and six patients underwent pneumonectomy were subjected to the study. All the clinicopathologic data including age, gender, smoking history, surgical treatment, postoperative complications, tumor staging and the follow-up information were investigated. Results: The 30-day and 90-day mortality rates were 3.2% and 6.2%, respectively. Postoperative complications developed in 149 patients (36.7%), mainly included arrhythmia, transfusion, pulmonary infection, bronchopleural fistula and acute respiratory distress syndrome. During the follow-up, 189 patients experienced a relapse, consisting of 51 patients with local recurrence and 138 with distant recurrence. The median survival time was 24.4 months and the overall 1-year, 3-year and 5-year survival rates were 82.7%, 50.9% and 32.5%, respectively. Moreover, the overall 1-year, 3-year, 5-year survival rates for patients with non-small cell lung cancer (NSCLC) were 84.1%, 52.1% and 32.5%, respectively and patients with small cell lung cancer (SCLC) were 56.1%, 38.5% and 28.8%, respectively. Among NSCLCs, adenocarcinomas had a worse prognosis than squamous carcinomas. Compared to right pneumonectomy, patients with left pneumonectomy had a better prognosis. Multivariable analysis revealed ICU stay, disease stage, nodal stage and adjuvant chemotherapy were all significant predictors of overall survival (OS). Conclusions: Pneumonectomy is still a valuable and effective treatment option for patients with advanced lung cancer. Surgeons should be more cautious when patients had higher disease stage, adenocarcinoma and right-side lung cancer. Neoadjuvant chemotherapy did not affect the prognosis. Pneumonectomy could also achieve acceptable survival outcomes in well-selected SCLC patients.

Predicting the recurrence risk factors and clinical outcomes of peripheral pulmonary adenocarcinoma ≤3 cm with wedge resection.

PURPOSE: This study was designed to investigate the risk factors of recurrence and survival of clinical stage I lung adenocarcinoma underwent wedge resection by the use of Shanghai Chest Hospital Lung Cancer Database. PATIENTS AND METHODS: A total of 746 patients with clinical stage I adenocarcinoma underwent wedge resection from 2010 to 2015 in our database were included in this study. Univariable and multivariable Cox proportional hazards regression were performed successively to select significant risk factors and then nomograms as well as the concordance indexes for RFS, OS and LCSS were developed, respectively. Kaplan-Meier survival curves were performed if necessary, with the identification of log-rank test. RESULTS: The 5-year RFS, OS and LCSS of clinical stage I adenocarcinoma underwent wedge resection were 86.1, 83.6 and 85.2%, respectively. There were three independent risk factors related with RFS (sex, pathology, pleural invasion), two related with OS (sex, volume ratio) and two with LCSS (sex, volume ratio) with the analysis of Cox regression and were selected to develop nomograms. The C-indexes of RFS, OS and LCSS were 0.767 (95% CI 0.667-0.867), 0.782 (95% CI 0.660-0.904) and 0.794 (95% CI 0.669-0.919), respectively. Lymphadenectomy did not show differences statistically but had tendencies of better RFS, OS and LCSS among the subgroup of invasive adenocarcinoma. CONCLUSION: Sex, pathology and pleural invasion could be recommended as criteria for clinical stage I adenocarcinoma undergoing wedge resection. And the larger the wedge volume and/or the smaller the tumor volume was, the better OS and LCSS were. If the volume ratio reached 10:1 or more, the survival rate was approximately 90% for both OS and LCSS. Whether lymphadenectomy was necessary for WR, especially in invasive adenocarcinoma, needed further research.

The indication of completion lobectomy for lung adenocarcinoma ≤3 cm after wedge resection during surgical operation.

PURPOSE: This retrospective study was designed to find out the potential indications of completion lobectomy (CL) during wedge resection (WR) operation among patients with lung adenocarcinoma (ADC) ≤3 cm, by the use of Shanghai Chest Hospital Lung Cancer Database. PATIENTS AND METHODS: There were totally 1938 patients in this study, including 746 WRs and 1192 CLs. The propensity score matching (PSM) was performed to minimize the effect of confounders. Univariable and multivariable cox regressions were analyzed to discover the independent risk factors of recurrence-free survival (RFS) and overall survival (OS). Subgroup analysis and Kaplan-Meier survival curves were performed if necessary. RESULTS: The 5-year RFS (86.1 vs 91.5%, p = 0.001 for unmatched group; 84 v 92%, p < 0.001 for PSM group) and OS (83.6 vs 91.7%, p < 0.001 for unmatched group; 81.6 vs 88.2%, p < 0.001 for PSM group) all indicated a better prognosis when conducting CL. Subgroup analysis suggested that WR was appropriate for non-invasive ADC. Three prognostic factors (sex, surgical approach and pleural invasion) were correlated with RFS and two (sex and surgical approach) corresponded with OS in invasive ADC through multivariable analysis. Non-lepidic-predominant component showed a better RFS and OS when CL was operated after WR in the subgroup of invasive ADC. CONCLUSION: CL was an appropriate remediation to WR when the existence of invasive ADC, especially non-lepidic-predominant one. While WR could be applied if non-invasive ADC was confirmed. Whether lepidic-predominant adenocarcinoma was fit for WR needed further study.

Visceral pleural invasion predict a poor survival among lung adenocarcinoma patients with tumor size ≤ 3cm.

INTRODUCTION: The impact of visceral pleural invasion (VPI) on survival remains controversial for patients with early stage non-small cell lung cancer (NSCLC). This study investigated the survival status of VPI among patients with lymph node-negative lung invasive adenocarcinoma smaller than 3cm. METHODS: We retrospectively reviewed 2537 consecutive patients with pathologic stage I lung invasive adenocarcinoma. All patients had received lobectomy and system lymph nodes resection. Patients were classified into 4 groups according to tumor size and visceral pleural invasion status. Disease-free survival (DFS) and overall survival (OS) were analyzed to evaluate survival difference between these groups. RESULTS: 548 patients with VPI while 1989 patients without VPI were included in this study. For patients with tumor size ≤2cm, patients with VPI had significant worse DFS (HR,4.85; 95% CI, 2.98-7.91; p = .000) and OS(HR,3.52; 95% CI, 1.59-7.78; p = .002) compared with non-VPI group. For patients with tumor size between 2-3cm, patients with VPI had significant worse DFS (HR, 1.72; 95% CI, 1.16-2.55; p = .006) but no significant OS (HR, 1.31; 95% CI, 0.76-2.24; p = .330) compared with non-VPI group. For patients with VPI, there were no survival difference between tumor size 2-3cm group and ≤2cm group for both DFS(HR,1.02; 95% CI, 0.65-1.61; p = .939) and OS(HR,1.45; 95% CI, 0.71-2.97; p = .315). CONCLUSIONS: VPI could predict a poor survival even for node-negative invasive lung adenocarcinoma patients with tumor size less than 3cm.