Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis In Vivo Using Endobronchial Optical Coherence Tomography.

Rationale: Idiopathic pulmonary fibrosis (IPF) affects the subpleural lung but is considered to spare small airways. Micro-computed tomography (micro-CT) studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. Objectives: In this study, EB-OCT was used to evaluate small airways in early IPF and control subjects in vivo. Methods: EB-OCT was performed in 12 subjects with IPF and 5 control subjects (matched by age, sex, smoking history, height, and body mass index). Subjects with IPF had early disease with mild restriction (FVC: 83.5% predicted), which was diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for usual interstitial pneumonia present) and less affected (some but not all criteria for usual interstitial pneumonia present). Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Measurements and Main Results: Compared with the number of bronchioles in control subjects (mean = 11.2/cm3; SD = 6.2), there was significant bronchiole reduction in subjects with IPF (42% loss; mean = 6.5/cm3; SD = 3.4; P = 0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; P < 0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; P = 0.024) sites. Stereology metrics showed that IPF-affected small airways were significantly larger, more distorted, and more irregular than in IPF-less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (P = 0.36-1.0). Conclusions: EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30% and 50%), even in areas minimally affected by disease, compared with matched control subjects. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

Tracheostomy is associated with decreased vasoactive-inotropic score in postoperative cardiac surgery patients on prolonged mechanical ventilation.

Objective: We sought to quantify the influence that tracheostomy placement has on the hemodynamic stability of postoperative cardiac surgery patients with persistent ventilatory requirements. Methods: A retrospective, single-center, and observational analysis of postoperative cardiac surgery patients with prolonged mechanical ventilation who underwent tracheostomy placement from 2018 to 2022 was conducted. Patients were excluded if receiving mechanical circulatory support or if they had an unrelated significant complication 3 days surrounding tracheostomy placement. Vasoactive and inotropic requirements were quantified using the Vasoactive-Inotrope Score. Results: Sixty-one patients were identified, of whom 58 met inclusion criteria. The median vasoactive-inotrope score over the 3 days before tracheostomy compared with 3 days after decreased from 3.35 days (interquartile range, 0-8.79) to 0 days (interquartile range, 0-7.79 days) (P = .027). Graphic representation of this trend demonstrates a clear inflection point at the time of tracheostomy. Also, after tracheostomy placement, fewer patients were on vasoactive/inotropic infusions (67.2% [n = 39] pre vs 24.1% [n = 14] post; P < .001) and sedative infusions (62.1% [n = 36] pre vs 27.6% [n = 16] post; P < .001). The percent of patients on active mechanical ventilation did not differ. Conclusions: The median vasoactive-inotrope score in cardiac surgery patients with prolonged mechanical ventilation was significantly reduced after tracheostomy placement. There was also a significant reduction in the number of patients on vasoactive/inotropic and sedative infusions 3 days after tracheostomy. These data suggest that tracheostomy has a positive effect on the hemodynamic stability of patients after cardiac surgery and should be considered to facilitate postoperative recovery.

Wedge Resection versus Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer Tumors ≤8 mm.

The objective of this study was to evaluate the overall survival of patients with ≤8 mm non-small cell lung cancer (NSCLC) who undergo wedge resection versus stereotactic body radiation therapy (SBRT). Kaplan-Meier analysis, multivariable Cox proportional hazards modeling, and propensity score-matched analysis were performed to evaluate the overall survival of patients with ≤8 mm NSCLC in the National Cancer Database (NCDB) from 2004 to 2017 who underwent wedge resection versus patients who underwent SBRT. The above-mentioned matched analyses were repeated for patients with no comorbidities. Patients who were coded in the NCDB as having undergone radiation because surgery was contraindicated due to patient risk factors (e.g., comorbid conditions, advance age, etc.) and those with a history of prior malignancy were excluded from analysis. Of the 1505 patients who had NSCLC ≤8 mm during the study period, 1339 (89%) patients underwent wedge resection, and 166 (11%) patients underwent SBRT. In the unadjusted analysis, multivariable Cox modeling and propensity score-matched analysis, wedge resection was associated with improved survival when compared to SBRT. These results were consistent in a sensitivity analysis limited to patients with no comorbidities.

A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery.

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

Predictors of Venous Thromboembolism After Lung Cancer Resection.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients undergoing oncologic operations. We sought to identify risk factors for postoperative VTE to define high-risk groups that may benefit from enhanced prophylactic measures. METHODS: A retrospective cohort analysis using The Society of Thoracic Surgeons General Thoracic Surgery Database was conducted on patients who underwent lung cancer resection between 2009 and 2021. Baseline characteristics and postoperative outcomes were compared between patients who did and did not develop a postoperative pulmonary embolism (PE) or deep venous thrombosis. Multivariable regression models identified risk factors associated with VTE. RESULTS: Of 57,531 patients who underwent lung cancer resection, a postoperative PE developed in 758 (1.3%). Patients with PE were more likely to be Black (12% vs 7%, P < .001), have interstitial fibrosis (3% vs 2%, P = .016), and prior VTE (12% vs 6%, P < .001). Postoperative PE was most likely to develop in patients with locally advanced disease who underwent bilobectomy (6% vs 4%, P < .001) or pneumonectomy (8% vs 5%, P < .001). Patients with postoperative PE had increased 30-day mortality (14% vs 3%, P < .001), reintubation (25% vs 8%, P < .001), and readmission (49% vs 15%, P < .001). On multivariable analysis, Black race (odds ratio, 1.74; 95% CI, 1.39-2.16; P < .001), interstitial fibrosis (odds ratio, 1.77; 95% CI, 1.15-2.72; P = .009), extent of resection, and increased operative duration were independently predictive of postoperative PE. A minimally invasive approach compared with thoracotomy was protective. CONCLUSIONS: Because nonmodifiable risk factors (Black race, interstitial fibrosis, and advanced-stage disease) predominate in postoperative PE and VTE-associated mortality is increased, enhanced perioperative prophylactic measures should be considered in high-risk cohorts.

Long-Term Survival of American Joint Committee on Cancer 8th Edition Staging Descriptors for Clinical M1a Non-Small Cell Lung Cancer.

BACKGROUND: The American Joint Committee on Cancer (AJCC) 8th edition TNM staging manual for non-small cell lung cancer (NSCLC) M1a descriptors includes tumors presenting with malignant pleural or pericardial effusion (ie, M1a-Effusion), pleural or pericardial nodule(s) (ie, M1a-Pleural), or separate tumor nodule(s) in a contralateral lobe (ie, M1a-Contralateral). RESEARCH QUESTION: Is M1a NSCLC presenting with malignant pleural or pericardial effusion associated with worse survival compared with other types of M1a NSCLC? STUDY DESIGN AND METHODS: Patients with cT1-4, N0-3, M1a NSCLC (satisfying a single M1a descriptor of M1a-Effusion, M1a-Pleural, or M1a-Contralateral), according to AJCC eighth edition staging criteria, in the National Cancer Database from 2010 to 2015 were included. Overall survival was evaluated by using Kaplan-Meier analysis, multivariable-adjusted Cox proportional hazards modeling, and propensity score matching. RESULTS: Of the 25,716 patients who met study eligibility criteria, 12,756 (49.6%) presented with M1a-Effusion tumors, 3,589 (14.0%) with M1a-Pleural tumors, and 9,371 (36.4%) with M1a-Contralateral tumors. In multivariable-adjusted analysis, compared to M1a-Effusion tumors, both M1a-Pleural tumors (hazard ratio, 0.68; 95% CI, 0.64-0.71; P < .001) and M1a-Contralateral tumors (hazard ratio, 0.66; 95% CI, 0.64-0.69; P < .001) were associated with better overall survival. No significant differences were found in overall survival between patients with M1a-Pleural tumors vs M1a-Contralateral tumors. In a propensity score-matched analysis of 5,581 patients with M1a-Effusion tumors and 5,581 patients with other M1a tumors (ie, M1a-Contralateral or M1a-Effusion), those with M1a-Effusion tumors had worse 5-year overall survival than patients with other M1a tumors (M1a-Effusion 6.4% [95% CI, 5.7-7.1] vs M1a-Other 10.6% [95% CI, 9.7-11.5]; P < .001). INTERPRETATION: In this national analysis of AJCC 8th edition cT1-4, N0-3, M1a NSCLC, tumors with malignant pleural or pericardial effusion were associated with worse overall survival than tumors with either pleural or contralateral pulmonary nodules. These findings may be taken into consideration for the upcoming ninth edition of the AJCC lung cancer staging guidelines.

Surgery for M1A Non-Small-Cell Lung Cancer With Additional Pulmonary Nodules in a Contralateral Lobe.

INTRODUCTION: Limited consensus exists on the optimal treatment strategy for clinical M1a non-small-cell lung cancer (NSCLC) presenting as a primary tumor with additional intrapulmonary nodules in a contralateral lobe ("M1a-Contra"). This study sought to compare long-term survival of patients with M1a-Contra tumors receiving multimodal therapy with versus without thoracic surgery. METHODS: Overall survival of patients with cT1-4, N0-3, M1a NSCLC with contralateral intrapulmonary nodules who received surgery as part of multimodal therapy ("Thoracic Surgery") versus systemic therapy with or without radiation ("No Thoracic Surgery") in the National Cancer Database from 2010 to 2015 was evaluated using Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching. RESULTS: Of the 5042 patients who satisfied study inclusion criteria, 357 (7.1%) received multimodal therapy including surgery. In multivariable-adjusted analysis, the Thoracic Surgery cohort had better overall survival than the No Thoracic Surgery cohort (HR: 0.66, 95% CI: 0.56-0.79, P < 0.001). In a propensity score-matched analysis of 386 patients, well-balanced on 12 common prognostic covariates, the Thoracic Surgery group had better 5-year overall survival than the No Thoracic Surgery group (P = 0.020). In propensity score-matched analyses stratified by clinical N status, Thoracic Surgery was associated with better overall survival than No Thoracic Surgery for patients with cN0 disease and cN1-2 disease. CONCLUSIONS: In this national analysis, multimodal treatment including surgery was associated with better overall survival than systemic therapy with or without radiation without surgery for patients with M1a-Contra tumors. These preliminary findings highlight the importance of further evaluation of surgery in a multidisciplinary treatment setting for M1a-Contra tumors.

Shortage of thoracic surgeons in the United States: Implications for treatment and survival for stage I lung cancer patients.

OBJECTIVES: To evaluate whether there is a shortage of thoracic surgeons in the United States and whether any potential shortage is impacting lung cancer treatment and outcomes. DESIGN: Using the US Area Health Resources File and Surveillance Epidemiology End Results database, we assessed the number of cardiothoracic surgeons per 100,000 people and the number of stage I non-small cell lung cancer (NSCLC) diagnoses in the US in 2010 versus 2018. Changes in the percentage of patients diagnosed with stage I NSCLC who underwent surgery and stereotactic body radiotherapy and changes in overall survival of patients with stage I NSCLC from 2010 to 2018 in the National Cancer Database were evaluated using multivariable logistic regression and Cox proportional hazards modeling. RESULTS: From 2010 to 2018, the number of cardiothoracic surgeons per 100,000 people in the US decreased by 12% (P < .001), while the number of patients diagnosed with stage I NSCLC increased by 40% (P < .001). Over the same period, the percentage of patients who underwent surgery for stage I NSCLC decreased from 81.0% to 72.3% (adjusted odds ratio, 0.59; 95% confidence interval, 0.55-0.63); this decrease was similarly seen in a subgroup of young and otherwise healthy patients. Greater decreases in the percentage of patients who underwent surgery in nonmetropolitan and underserved regions corresponded with worse improvements in survival among patients in these regions from 2010 to 2018. CONCLUSIONS: Recent declines in the US cardiothoracic surgery workforce may have led to significantly fewer patients undergoing surgery for stage I NSCLC and worsening disparities in survival between different patient populations.

Role of Adjuvant Chemotherapy in Early-Stage Combined Small Cell Lung Cancer.

BACKGROUND: The role of adjuvant therapy in completely resected primary tumors that have components of both non-small cell lung cancer and small cell lung cancer (combined SCLC) is poorly understood. We sought to determine the potential benefits of adjuvant chemotherapy in patients who undergo complete resection for early-stage combined SCLC. METHODS: Overall survival of patients with pathologic T1-2 N0 M0 combined SCLC who underwent complete resection in the National Cancer Database from 2004 to 2017, stratified by adjuvant chemotherapy vs surgery alone, was evaluated by multivariable Cox proportional hazards modeling and propensity score-matched analysis. Patients treated with induction therapy and those who died within 90 days of surgery were excluded from analysis. RESULTS: Of 630 patients who had pT1-2 N0 M0 combined SCLC during the study period, 297 patients (47%) underwent complete R0 resection. Adjuvant chemotherapy was administered to 63% of patients (n = 188), and 37% of patients underwent surgery alone (n = 109). In unadjusted analysis, the 5-year overall survival was 61.6% (95% CI, 50.8-70.7) for patients who underwent surgery alone and 66.4% (95% CI, 58.4-73.3) for patients who underwent adjuvant chemotherapy. In multivariable and propensity score-matched analysis, there were no significant differences in overall survival between adjuvant chemotherapy and surgery alone (adjusted hazard ratio, 1.16; 95% CI, 0.73-1.84). These findings were consistent when limited to patients who underwent lobectomies or to healthier patients who have at most 1 major comorbidity. CONCLUSIONS: In this national analysis, patients with pT1-2 N0 M0 combined SCLC treated with surgical resection alone have similar outcomes to those who undergo adjuvant chemotherapy.

B cell-dependent subtypes and treatment-based immune correlates to survival in stage 3 and 4 lung adenocarcinomas.

Lung cancer is the leading cause of cancer-related deaths worldwide. Surgery and chemoradiation are the standard of care in early stages of non-small cell lung cancer (NSCLC), while immunotherapy is the standard of care in late-stage NSCLC. The immune composition of the tumor microenvironment (TME) is recognized as an indicator for responsiveness to immunotherapy, although much remains unknown about its role in responsiveness to surgery or chemoradiation. In this pilot study, we characterized the NSCLC TME using mass cytometry (CyTOF) and bulk RNA sequencing (RNA-Seq) with deconvolution of RNA-Seq being performed by Kassandra, a recently published deconvolution tool. Stratification of patients based on the intratumoral abundance of B cells identified that the B-cell rich patient group had increased expression of CXCL13 and greater abundance of PD1+ CD8 T cells. The presence of B cells and PD1+ CD8 T cells correlated positively with the presence of intratumoral tertiary lymphoid structures (TLS). We then assessed the predictive and prognostic utility of these cell types and TLS within publicly available stage 3 and 4 lung adenocarcinoma (LUAD) RNA-Seq datasets. As previously described by others, pre-treatment expression of intratumoral 12-chemokine TLS gene signature is associated with progression free survival (PFS) in patients who receive treatment with immune checkpoint inhibitors (ICI). Notably and unexpectedly pre-treatment percentages of intratumoral B cells are associated with PFS in patients who receive surgery, chemotherapy, or radiation. Further studies to confirm these findings would allow for more effective patient selection for both ICI and non-ICI treatments.

Wedge Resection Versus Segmentectomy for Older Patients With Stage IA Non-Small-Cell Lung Cancer.

INTRODUCTION: Anatomic lung resection remains the standard of care for early-stage non-small-cell lung cancer (NSCLC), but wedge resection may offer similar survival in older adult patients. The objective of this study was to evaluate the survival of patients aged 80 y and older undergoing wedge resection versus segmentectomy for stage IA NSCLC using a large clinical registry. METHODS: Patients aged 80 y and older in the National Cancer Database who underwent wedge resection or segmentectomy for cT1a-b N0 M0 NSCLC between 2004 and 2018 were identified for an analysis. Survival was assessed using multivariable Cox proportional hazards analysis, propensity-score matching, and inverse probability weighting. A subgroup analysis of patients who underwent lymph node evaluation with their wedge resection or segmentectomy was also performed. RESULTS: Of the 2690 patients identified, 2272 (84%) underwent wedge resection and 418 (16%) underwent segmentectomy. Wedge resection was associated with worse 5-year overall survival relative to segmentectomy in multivariable-adjusted (adjusted Hazard Ratio: 1.26, [1.06-1.51], P = 0.01) and propensity score-matched analysis (49% [95% confidence interval {CI}: 42%-55%] versus 59% [95% CI: 52%-65%], P = 0.02). Among a subgroup of 1221 wedge resection and 347 segmentectomy patients who also received intraoperative lymph node evaluation, however, there were no significant differences in 5-year survival in multivariable-adjusted (adjusted Hazard Ratio: 1.12, [0.90-1.39], P = 0.31) or propensity score-matched analysis (55% [95% CI: 48%-62%] versus 61% [95% CI: 54%-68%], P = 0.10). CONCLUSIONS: In this national analysis, there were no significant differences in survival between older adult patients with stage IA NSCLC who underwent wedge resection versus segmentectomy when a lymph node evaluation was performed.

Open, Video- and Robot-Assisted Thoracoscopic Lobectomy for Stage II-IIIA Non-Small Cell Lung Cancer.

BACKGROUND: This study compares the short- and long-term outcomes of open vs robotic vs video-assisted thoracoscopic surgery (VATS) lobectomy for stage II-IIIA non-small-cell lung cancer (NSCLC). METHODS: Outcomes of patients with stage II-IIIA NSCLC (excluding T4 tumors) who received open and minimally invasive surgery (MIS) lobectomy in the National Cancer Database from 2010 to 2017 were assessed using propensity score-matched analysis. RESULTS: A propensity score-matched analysis of 4652 open and 4652 MIS patients demonstrated a decreased median length of stay associated with MIS compared with open lobectomy (5 vs 6 days; P < .001). There were no significant differences in 30-day mortality, 30-day readmission, or overall survival between the open and MIS groups. A propensity score-matched analysis of 1186 VATS and 1186 robotic patients showed that compared with VATS, the robotic approach was associated with no significant differences in 30-day mortality, 30-day readmission, and overall survival. However, the robotic group had a decreased median length of stay compared with VATS (4 vs 5 days; P < .001). The conversion rate was also significantly lower for robotic compared with VATS lobectomy (8.9% vs 15.9%, P < .001). CONCLUSIONS: No significant differences were found in long-term survival between open and MIS lobectomy and between VATS and robotic lobectomy for stage II-IIIA NSCLC. However, the MIS approach was associated with a decreased length of stay compared with the open approach. The robotic approach was associated with decreased length of stay and decreased conversion rate compared with the VATS approach.

Diagnostic Accuracy of Endobronchial Optical Coherence Tomography for the Microscopic Diagnosis of Usual Interstitial Pneumonia.

Rationale: Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. High-resolution computed tomography has limited resolution, and surgical lung biopsy (SLB) carries risks of morbidity and mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis. Objectives: We performed a prospective diagnostic accuracy study of EB-OCT in patients with ILD with a low-confidence diagnosis undergoing SLB. The primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern. Methods: EB-OCT was performed immediately before SLB. The resulting EB-OCT images and histopathology were interpreted by blinded, independent pathologists. Clinical diagnosis was obtained from the treating pulmonologists after SLB, blinded to EB-OCT. Measurements and Main Results: We enrolled 31 patients, and 4 were excluded because of inconclusive histopathology or lack of EB-OCT data. Twenty-seven patients were included in the analysis (16 men, average age: 65.0 yr): 12 were diagnosed with UIP and 15 with non-UIP ILD. Average FVC and DlCO were 75.3% (SD, 18.5) and 53.5% (SD, 16.4), respectively. Sensitivity and specificity of EB-OCT was 100% (95% confidence interval, 75.8-100.0%) and 100% (79.6-100%), respectively, for both histopathologic UIP and clinical diagnosis of IPF. There was high agreement between EB-OCT and histopathology for diagnosis of ILD fibrosis pattern (weighted κ: 0.87 [0.72-1.0]). Conclusions: EB-OCT is a safe, accurate method for microscopic ILD diagnosis, as a complement to high-resolution computed tomography and an alternative to SLB.

Anatomy and Embryology of the Thoracic Outlet.

The thoracic outlet is the space between the thorax and axilla through which the subclavian vein, subclavian artery, and brachial plexus travel from their central origins to their peripheral termini. Its bounds include the clavicle, first thoracic rib, insertion of the pectoralis minor muscle onto the coracoid process of the humerus, and the sternum. It contains three areas: the scalene triangle, the costoclavicular space, and the subcoracoid or pectoralis minor space. Aberrant anatomy is common in the thoracic outlet and may predispose patients to compression of the neurovascular bundle and development of clinical thoracic outlet syndrome (TOS). Much of this aberrancy is explained by the embryologic origins of the structures that comprise the thoracic outlet. A thorough understanding of this anatomy and embryology is therefore critical to the understanding of TOS.