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Objectives: The aim of this study was to analyse outcomes of lung cancer in the elderly., Methods: A retrospective analysis was performed of patients in the National Cancer Database with NSCLC from 2004 to 2017 grouped into 2 categories: 70-79 years (A) and 80-90 years (B). Patients with multiple malignancies were excluded. Kaplan-Meier curves estimated the overall survival for each age group based on stage., Results: In total, 466 051 patients were included. Less-invasive techniques (imaging and cytology) diagnosed cancer as a function of age: 14.6% in A vs 21.3% in B [P < 0.001, standardized mean difference (SMD) 0.175]. Clinical stage IA was least common in B (15%) compared to 17.3% in A (P < 0.001, SMD 0.079). Approximately 83.0% in B did not receive surgery compared to 70.0% in A (P < 0.001, SMD 0.299). Of the 83.0%, 8.0% were considered poor surgical candidates because of age or comorbidities compared with 6.2% in A (P < 0.001, SMD 0.299) For 71.0% in B, surgery was not the first treatment plan compared to 62.0% in A (P < 0.001, SMD 0.299). Survival curves showed worse prognosis for each clinical and pathologic stage for B compared to A., Conclusions: Patients older than 80 years present less frequently as clinical stage IA, are less commonly offered surgical intervention and are more frequently diagnosed using less accurate measures. They also have worse outcomes for each stage compared to younger patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: To evaluate the impact of empiric tissue flaps on bronchopleural fistula (BPF) rates after pneumonectomy., Methods: Patients who underwent pneumonectomy between January 2001 and December 2019 were included. Primary end point was development of BPF. Secondary end points were impact of flap type on BPF rates, time to BPF development, and perioperative mortality., Results: During the study period, 383 pneumonectomies were performed; 93 were extrapleural pneumonectomy. Most pneumonectomy cases had empiric flap coverage, with greater use in right-sided operations (right: 97%, 154/159; left: 80%, 179/224, P < .001). Empiric flaps harvested included intercostal, latissimus dorsi, serratus anterior, omentum, pectoralis major, pericardial fat/thymus, pericardium, and pleura. BPF occurred in 10.4% of the entire cohort but decreased to 6.6% when extrapleural pneumonectomy cases were excluded; 90% (36/40) of BPFs occurred on the right side (P < .001). Median time to develop BPF was 63 days, and 90-day mortality was greater in patients with BPF (12.5% BPF vs 7.4% non-BPF, P < .0001). Intercostal muscle had the lowest rate of BPF (4.5%), even in right-sided operations (8.7%). In contrast, larger muscle flaps such as latissimus dorsi (21%) and serratus anterior (33%) had greater rates of BPF, but the sample size was small in these cohorts., Conclusions: Empiric bronchial stump coverage should be performed in all right pneumonectomy cases due to greater risk of BPF. In our series, intercostal muscle flaps had low BPF rates, even in right-sided operations. Coverage of the left pneumonectomy stump is unnecessary due to low incidence of BPF in these cases., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Recommendations for intraoperative lymph node evaluation are uniform regardless of whether a primary tumor is clinical T1a or T2a according to TNM 8th edition for stage I non-small cell lung cancer (NSCLC). We quantified nodal disease risk in patients with T1a disease (≤1 cm)., Methods: The National Cancer Database was queried for clinical T1a N0 M0 primary NSCLCs ≤1 cm undergoing lobectomy with mediastinal nodal evaluation from 2004-2014. Nodal disease risk was analyzed as a function of demographics and tumor characteristics., Results: Among 2157 cases, 6.7% had occult nodal disease: 5.1% occult N1 and 1.6% N2. Adenocarcinoma (7.5%), large cell carcinoma (25%), and poor differentiation (11.8%) or undifferentiated/anaplastic (25.0%) had high rates of combined pN1 and N2 disease (P < .001). In univariable analysis, odds of pathologic N1, N2, or N1/N2 nodal disease with respect to N0 was greatest for large cell carcinoma (ref. adenocarcinoma odds ratio [OR] 4.31, 3.62, 4.12 respectively; all P < .05), and anaplastic grade (OR 10.71, 13.09, 11.55). Bronchoalveolar adenocarcinomas had the lowest odds (OR 0.41, 0.11, 0.32) and squamous cell carcinoma had lower odds for N2 (OR 0.29, all P < .05). In multivariable analysis only bronchoalveolar adenocarcinomas had lower odds of pathologic N2 and N1/N2 disease with respect to N0. Worsening grade remained significant for pathologic N1 and N1/N2 disease (both P < .05)., Conclusions: A significant rate (6.7%) of occult nodal disease is present in primary NSCLCs ≤1 cm. Risk increases with certain histology and worsening grade. We recommend mandatory systematic hilar and mediastinal nodal evaluation for T1a NSCLC tumors for accurate staging and adjuvant therapy., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Lobectomy is a standard treatment for stage I non-small cell lung cancer, but a significant proportion of patients are considered at high risk for complications, including mortality, after lobectomy and might not be candidates. Identifying who is at risk is important and in evolution. The objective of The American Association for Thoracic Surgery Clinical Practice Standards Committee expert panel was to review important considerations and factors in assessing who is at high risk among patients considered for lobectomy., Methods: The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an expert panel that developed an expert consensus document after systematic review of the literature. The expert panel generated a priori a list of important risk factors in the determination of high risk for lobectomy. A survey was administered, and the expert panel was asked to grade the relative importance of each risk factor. Recommendations were developed using discussion and a modified Delphi method., Results: The expert panel survey identified the most important factors in the determination of high risk, which included the need for supplemental oxygen because of severe underlying lung disease, low diffusion capacity, the presence of frailty, and the overall assessment of daily activity and functional status. The panel determined that factors, such as age (as a sole factor), were less important in risk assessment., Conclusions: Defining who is at high risk for lobectomy for stage I non-small cell lung cancer is challenging, but remains critical. There was impressive strong consensus on identification of important factors and their hierarchical ranking of perceived risk. The panel identified several key factors that can be incorporated in risk assessment. The factors are evolving and as the population ages, factors such as neurocognitive function and frailty become more important. A minimally invasive approach becomes even more critical in this older population to mitigate risk. The determination of risk is a clinical decision and judgement, which should also take into consideration patient perspectives, values, preferences, and quality of life., (Copyright © 2021. Published by Elsevier Inc.)

Background: We analyzed the association between neoadjuvant chemoradiation in patients undergoing bronchial sleeve resection with the incidence of postoperative pulmonary and airway complications., Methods: After instructional review board approval we performed a retrospective review of a prospectively maintained database of 136 patients who underwent sleeve resection in our institution between January 1998 and December 2016. Administration of neoadjuvant chemoradiation treatment was the studied exposure. Outcomes of interest were rates of postoperative pulmonary and airway complications. Nonparametric testing of demographic, surgical, and pathologic characteristics and morbidity was performed. Logistic regression models evaluated postoperative pulmonary complications and airway complications. Analysis was performed using Stata/IC 15., Results: We analyzed 136 patients (18 underwent neoadjuvant chemoradiation), 77 (57%) of whom had non-small cell lung cancer. Postoperative pulmonary complications were observed in 44 of 136 patients (32%). Incidences of pulmonary complications were higher in the neoadjuvant chemoradiation group compared with the non-neoadjuvant radiation group (15/18 patients [83%] vs 29/118 patients [25%], respectively; P < .001). Likewise, rates of pneumonia, atelectasis, respiratory insufficiency, bronchial stenosis, prolonged air leak, bronchopleural fistula, and completion pneumonectomy (2/18 [11%]) were higher in the neoadjuvant chemoradiation group, reaching statistical significance in all cases except bronchial stenosis and prolonged air leak. Only neoadjuvant chemoradiation therapy remained significant for postoperative pulmonary and airway complications on logistic regression (both P < .05) CONCLUSIONS: Patients who undergo neoadjuvant chemoradiation before sleeve resection are at an increased risk of pulmonary and airway complications., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Surgical palliation can improve quality of life, provide local control, and extend survival. However, oncologists often view surgical intervention as a drastic measure with prohibitive morbidity. During the past decade, surgical palliation has played a role in the management of many metastatic malignancies, including those of the colon, breast, prostate, and kidney. In concert with this, the morbidity and mortality associated with surgical interventions has continued to decline. We present 2 patients with thoracic sarcoma recurrences after pneumonectomy that were associated with symptomatic compression of pulmonary vessels and airway. Both patients underwent surgical resection, with immediate relief of symptoms, improved quality of life, and extended survival., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Escape from TGF-beta inhibition of proliferation is a hallmark of multiple cancers including lung cancer. We explored the role of ELF, crucial TGF-beta adaptor protein identified from endodermal progenitor cells, in lung carcinogenesis and cell-cycle regulation. Interestingly, elf-/- mice develop multiple defects that include lung, liver, and cardiac abnormalities. Four out of 6 lung cancer and mesothelioma cell lines displayed deficiency of ELF expression with increased CDK4 expression. Immunohistochemistry and Western blot analysis of primary human lung cancers also showed decreased ELF expression and overexpression of CDK4. Moreover, rescue of ELF in ELF-deficient cell lines decreased the expression of CDK4 and resulted in accumulation of G1/S checkpoint arrested cells. These results suggest that disruption in TGF-beta signaling mediated by loss of ELF in lung cancer leads to cell-cycle deregulation by modulating CDK4 and ELF highlights a key role of TGF-beta adaptor protein in suppressing early lung cancer.

Hypothesis: That aggressive surgical treatment of lung cancer (LC) is justified by stage-based outcome in immunosuppressed solid organ transplant recipients., Design: Case series., Setting: University hospital., Patients: Lung cancer developed in 15 patients (0.28%) among a solid organ transplant recipient population of 5400 accrued at our institution over a 25-year period., Main Outcome Measures: Smoking prevalence, subtypes and stages of LC represented, operative morbidity, and survival., Results: The mean time from transplantation to the diagnosis of LC was 76 months (range, 9-192 months). Eight patients received kidneys; 3, lungs; and 4, hearts. Only 11 patients (73%) had a smoking history (mean, 66 pack-years). The following carcinomas developed in our patient population: adenocarcinoma, 6 patients; squamous cell, 5; large cell undifferentiated, 2; bronchoalveolar, 1; and small cell, 1. Eight patients (53%) presented with inoperable stage IIIB or IV disease. The remaining patients presented in stages IA (n = 2), IB (n = 1), IIB (n = 2), and IIIA (n = 2); all underwent resection. No major postoperative complications occurred. All patients with stage IIIB or greater disease with or without treatment died quickly (mean survival, 1.4 months; range, 0.33-3.0 months). All patients with stage IIB or less remain alive a mean of 37 months after resection. Patients with stage IIIA survived only a mean of 6.0 months despite resection., Conclusions: Regarding LCs in transplant recipients compared with LCs in the nontransplant population, we find that (1) there is an increased incidence among nonsmokers; (2) death occurs rapidly in unresected patients; (3) resection carries a low morbidity rate; and (4) resection seems to offer a high chance of cure in those with cancers staged IIB or less.

Objective: In undiseased lung epithelial cells, apoptosis is an evolutionarily conserved and genetically regulated form of cell suicide which plays an important role in development and in the maintenance of tissue homeostasis. Neoplastic lung cells develop the ability to deregulate growth by alterations in these genes which control apoptosis. Genomic profiling was used to compare gene expression levels in early stage lung adenocarcinomas and nonneoplastic pulmonary tissue in order to comprehensively identify alterations in the process of apoptosis., Methods: RNA extracted from node negative, poorly differentiated lung adenocarcinomas (15 patients) and nonneoplastic pulmonary tissue (5 patients) was hybridized to oligonucleotide microarray filters containing 44,363 genes. Ontological classification was used to extract genes involved with apoptosis. Further analysis discovered a subset of differentially expressed genes for further study., Results: Of the 308 apoptotic genes on the microarray filters, 24 genes were predicted to be differentially expressed in lung adenocarcinomas. Alterations in several genes (i.e., Akt, BcL-xL, PTEN, FAS) are consistent with the literature. We also identified 10 novel genes that have not been described in nonsmall cell lung cancer (i.e., RIP, Caspase 1, PDK-1)., Conclusions: These results identified several potential apoptotic genes altered in lung cancer.