Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer.

BACKGROUND: The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy. METHODS: We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions. RESULTS: From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group. CONCLUSIONS: In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).

Impact of Surgical Positioning on the Occurrence of Postoperative Ipilateral Shoulder Pain After Lung Resection by Video-Assisted Thoracoscopy: A Randomized Trial.

OBJECTIVE: The aim of this study was to evaluate the impact of the ipsilateral arm position on ipsilateral shoulder pain after lung cancer resection by video-assisted thoracic surgery. DESIGN: A prospective randomized controlled trial. SETTING: A single academic center study. PARTICIPANTS: Patients undergoing video-assisted thoracic surgery pulmonary resection for cancer at the Institut Universitaire de Cardiologie et de Pneumologie de Québec from May 2020 to May 2022 were included. INTERVENTIONS: Patients randomly were assigned with a 1:1 ratio to a supported or suspended ipsilateral arm position. MEASUREMENTS AND MAIN RESULTS: Ipsilateral shoulder pain incidence, pain score, and opioid use were recorded in the postanesthesia care unit (PACU) on postoperative days 1 and 2. One hundred thirty-three patients were randomized, 67 in the suspended-arm group and 66 in the supported-arm group. Of the patients, 31% reported ipsilateral shoulder pain in the PACU with no difference between groups (19/67 [28.4%] v 22/66 patients (33.3%), p = 0.5767). There was no significant difference between the pain score in the PACU (3 [0-6] v 4 [0-6], p = 0.9055) at postoperative day 1 (4 [2-6] v 3 [2-5], p = 0.4113) and at postoperative day 2 (2 [0-5] v 2 [1-4], p = 0.9508). Ipsilateral shoulder pain score decreased rapidly on postoperative day 2. There was no statistical difference in opioid and gabapentinoid use between the groups. CONCLUSIONS: Ipsilateral arm position seems to have no impact on ipsilateral shoulder pain.

Monitoring of Cardiorespiratory Parameters during Sleep Using a Special Holder for the Accelerometer Sensor.

Sleep is extremely important for physical and mental health. Although polysomnography is an established approach in sleep analysis, it is quite intrusive and expensive. Consequently, developing a non-invasive and non-intrusive home sleep monitoring system with minimal influence on patients, that can reliably and accurately measure cardiorespiratory parameters, is of great interest. The aim of this study is to validate a non-invasive and unobtrusive cardiorespiratory parameter monitoring system based on an accelerometer sensor. This system includes a special holder to install the system under the bed mattress. The additional aim is to determine the optimum relative system position (in relation to the subject) at which the most accurate and precise values of measured parameters could be achieved. The data were collected from 23 subjects (13 males and 10 females). The obtained ballistocardiogram signal was sequentially processed using a sixth-order Butterworth bandpass filter and a moving average filter. As a result, an average error (compared to reference values) of 2.24 beats per minute for heart rate and 1.52 breaths per minute for respiratory rate was achieved, regardless of the subject's sleep position. For males and females, the errors were 2.28 bpm and 2.19 bpm for heart rate and 1.41 rpm and 1.30 rpm for respiratory rate. We determined that placing the sensor and system at chest level is the preferred configuration for cardiorespiratory measurement. Further studies of the system's performance in larger groups of subjects are required, despite the promising results of the current tests in healthy subjects.

Outcomes Following Surgical Lung Biopsy for Interstitial Lung Diseases: A Monocenter Experience.

BACKGROUND: Surgical lung biopsy (SLB) is considered in the investigation of interstitial lung diseases (ILDs) when a complete clinical evaluation and a multidisciplinary discussion (MDD) do not allow the clinician to make a confident diagnosis. Owing to the risk of the procedure, an appropriate assessment of the risk/benefit ratio prior to the intervention is recommended. We aimed to assess the postoperative outcomes and diagnostic yield of SLB for the investigation of ILD in a tertiary care institution. METHODS: We conducted a retrospective cohort study of consecutive subjects who underwent a SLB for the investigation of ILD in our center from 2009 to 2020. The postoperative mortality and complications rates as well as the diagnostic yield of the procedure were assessed. RESULTS: Of the 1,805 patients newly investigated for ILD in our center from 2009 to 2020, 71 (3.93%) underwent a SLB. At days 30 and 90, the mortality rates were 0 and 2.8%, whereas 4.3 and 7.6% patients experienced an acute ILD exacerbation, respectively. In addition, 4 (5.8%) patients experienced infectious complications and 5 (7.0%) presented prolonged air leaks (all within 30 days). A definite pathological diagnosis was made in 47 (66.2%) patients. Following postoperative MDD, a confident diagnosis was made in 61 patients (85.9%) and resulted in a change of therapy in 49 (69.0%) patients. CONCLUSION: SLB for the diagnosis of unclassifiable ILDs is associated with low mortality but significant morbidity. However, it results in a confident diagnosis and a change in therapy in the majority of patients.

Bronchial blocker versus left double-lumen endotracheal tube in video-assisted thoracoscopic surgery: a randomized-controlled trial examining time and quality of lung deflation.

INTRODUCTION: Double-lumen endotracheal tubes (DL-ETT) and bronchial blockers (BB) have both been used for lung isolation in video-assisted thoracic surgery (VATS). Though not well studied, it is widely thought that a DL-ETT provides faster and better quality lung collapse. The aim of this study was to compare a BB technique vs a left-sided DL-ETT strategy with regard to the time and quality of lung collapse during one-lung ventilation (OLV) for elective VATS. METHODS: Forty patients requiring OLV for VATS were randomized to receive a BB (n = 20) or a left-sided DL-ETT (n = 20). The primary endpoint was the time from pleural opening (performed by the surgeon) until complete lung collapse. The time was evaluated offline by reviewing video recorded during the VATS. The quality of lung deflation was also graded offline using a visual scale (1 = no lung collapse; 2 = partial lung collapse; and 3 = total lung collapse) and was recorded at several time points after pleural incision. The surgeon also graded the time to complete lung collapse and quality of lung deflation during the procedure. The surgeon's guess as to which device was used for lung isolation was also recorded. RESULTS: Of the 40 patients enrolled in the study, 20 patients in the DL-ETT group and 18 in the BB group were analyzed. There mean (standard deviation) time to complete lung collapse of the operative lung was significantly faster using the BB compared with using the DL-ETT [7.5 (3.8) min vs 36.6 (29.1) min, respectively; mean difference, 29.1 min; 95% confidence interval, 1.8 to 7.2; P < 0.001]. Overall, a higher proportion of patients in the BB group than in the DL-ETT group achieved a quality of lung collapse score of 3 at five minutes (57% vs 6%, respectively; P < 0.004), ten minutes (73% vs 14%, respectively; P = 0.005), and 20 min (100% vs 25%, respectively; P = 0.002) after opening the pleura. The surgeon incorrectly guessed the type of device used in 78% of the BB group and 50% of the DL-ETT group (P = 0.10). CONCLUSION: The time and quality of lung collapse during OLV for VATS was significantly better when using a BB than when using a left-sided DL-ETT. Surgeons could not reliably determine which device was being used based on the time and quality of lung collapse. This trial was registered at ClinicalTrials.gov number, NCT01615263.

Susceptibility loci for lung cancer are associated with mRNA levels of nearby genes in the lung.

Recent studies identified three genetic loci reproducibly associated with lung cancer in populations of European ancestry, namely 15q25, 5p15 and 6p21. The goals of this study are first to confirm whether these loci are associated with lung cancer in a French Canadian population and second to identify disease-associated single nucleotide polymorphisms (SNPs) influencing messenger RNA (mRNA) expression levels of genes in the lung, that is expression quantitative trait loci (eQTLs). SNPs were genotyped in 420 patients undergoing lung cancer surgery and compared with 3151 controls of European ancestry. Genome-wide gene expression levels in non-tumor lung tissues of the same 420 patients were also measured to identify eQTLs. Significant eQTLs were then followed-up in two replication sets (n = 339 and 363). SNPs found in the three susceptibility loci were associated with lung cancer in the French Canadian population. Strong eQTLs were found on chromosome 15q25 with the expression levels of CHRNA5 (P = 2.23 × 10(-) (22) with rs12907966). The CHRNA5-rs12907966 eQTL was convincingly validated in the two replication sets (P = 3.46 × 10(-) (16) and 2.01 × 10(-) (15)). On 6p21, a trend was observed for rs3131379 to be associated with the expression of APOM (P = 3.58 × 10(-) (4)) and validated in the replication sets (P = 1.11 × 10(-) (8) and 6.84 × 10(-) (4)). On 5p15, no significant eQTLs were found. This study confirmed that chromosomes 15q25, 5p15 and 6p21 harbored susceptibility loci for lung cancer in French Canadians. Most importantly, this study suggests that the risk alleles at 15q25 and 6p21 may mediate their effect by regulating the mRNA expression levels of CHRNA5 and APOM in the lung.

Genetic regulation of gene expression in the lung identifies CST3 and CD22 as potential causal genes for airflow obstruction.

BACKGROUND: COPD is a complex chronic disease with poorly understood pathogenesis. Integrative genomic approaches have the potential to elucidate the biological networks underlying COPD and lung function. We recently combined genome-wide genotyping and gene expression in 1111 human lung specimens to map expression quantitative trait loci (eQTL). OBJECTIVE: To determine causal associations between COPD and lung function-associated single nucleotide polymorphisms (SNPs) and lung tissue gene expression changes in our lung eQTL dataset. METHODS: We evaluated causality between SNPs and gene expression for three COPD phenotypes: FEV(1)% predicted, FEV(1)/FVC and COPD as a categorical variable. Different models were assessed in the three cohorts independently and in a meta-analysis. SNPs associated with a COPD phenotype and gene expression were subjected to causal pathway modelling and manual curation. In silico analyses evaluated functional enrichment of biological pathways among newly identified causal genes. Biologically relevant causal genes were validated in two separate gene expression datasets of lung tissues and bronchial airway brushings. RESULTS: High reliability causal relations were found in SNP-mRNA-phenotype triplets for FEV(1)% predicted (n=169) and FEV(1)/FVC (n=80). Several genes of potential biological relevance for COPD were revealed. eQTL-SNPs upregulating cystatin C (CST3) and CD22 were associated with worse lung function. Signalling pathways enriched with causal genes included xenobiotic metabolism, apoptosis, protease-antiprotease and oxidant-antioxidant balance. CONCLUSIONS: By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified CST3 and CD22 as potential causal genes for airflow obstruction. This study also augmented the understanding of previously described COPD pathways.

Lobectomy, segmentectomy, or wedge resection for peripheral clinical T1aN0 non-small cell lung cancer: A post hoc analysis of CALGB 140503 (Alliance).

BACKGROUND: We have recently reported the primary results of CALGB 140503 (Alliance), a randomized trial in patients with peripheral cT1aN0 non-small cell lung cancer (American Joint Committee on Cancer seventh) treated with either lobar resection (LR) or sublobar resection (SLR). Here we report differences in disease-free survival (DFS), overall survival (OS) and lung cancer-specific survival (LCSS) between LR, segmental resection (SR), and wedge resection (WR). We also report differences between WR and SR in terms of surgical margins, rate of locoregional recurrence (LRR), and expiratory flow rate at 6 months postoperatively. METHODS: Between June 2007 and March 2017, a total of 697 patients were randomized to LR (n = 357) or SLR (n = 340) stratified by clinical tumor size, histology, and smoking history. Ten patients were converted from SLR to LR, and 5 patients were converted from LR to SLR. Survival endpoints were estimated using the Kaplan-Maier estimator and tested by the stratified log-rank test. The Kruskal-Wallis test was used to compare margins and changes in forced expiratory volume in 1 second (FEV1) between groups, and the χ2 test was used to test the associations between recurrence and groups. RESULTS: A total of 362 patients had LR, 131 had SR, and 204 had WR. Basic demographic and clinical and pathologic characteristics were similar in the 3 groups. Five-year DFS was 64.7% after LR (95% confidence interval [CI], 59.6%-70.1%), 63.8% after SR (95% CI, 55.6%-73.2%), and 62.5% after WR (95% CI, 55.8%-69.9%) (P = .888, log-rank test). Five-year OS was 78.7% after LR, 81.9% after SR, and 79.7% after WR (P = .873, log-rank test). Five-year LCSS was 86.8% after LR, 89.2% after SR, and 89.7% after WR (P = .903, log-rank test). LRR occurred in 12% after SR and in 14% after WR (P = .295). At 6 months postoperatively, the median reduction in % FEV1 was 5% after WR and 3% after SR (P = .930). CONCLUSIONS: In this large randomized trial, LR, SR, and WR were associated with similar survival outcomes. Although LRR was numerically higher after WR compared to SR, the difference was not statistically significant. There was no significant difference in the reduction of FEV1 between the SR and WR groups.

Secondary Analysis of the Rate of Second Primary Lung Cancer From Cancer and Leukemia Group B 140503 (Alliance) Trial of Lobar Versus Sublobar Resection for T1aN0 Non-Small-Cell Lung Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Patients with early-stage non-small-cell lung cancer (NSCLC) who undergo curative surgical resection are at risk for developing second primary lung cancer (SPLC). Cancer and Leukemia Group B 140503 (Alliance) was a multicenter, international, randomized, phase III trial in patients with stage T1aN0 NSCLC (using the TNM staging system seventh edition) and demonstrated the noninferiority for disease-free survival between sublobar resection (SLR) and lobar resection (LR). After surgery, patients underwent computed tomography surveillance as defined by the protocol. The determination of a SPLC was done by the treating physician and recorded in the study database. We performed an analysis of the rate of SPLC (per patient per year) and the 5-year cumulative incidence in the study population and within the SLR and LR arms. Median follow-up was 7 years. The rate per patient per year in the study population, in the SLR arm, and in the LR arm was 3.4% (95% CI, 2.9 to 4.1), 3.8% (95% CI, 2.9 to 4.9), and 3.1% (95% CI, 2.4 to 4.1), respectively. The estimated 5-year cumulative incidence of SPLC in the study population, SLR arm, and LR arm was 15.9% (95% CI, 12.9 to 18.9), 17.2% (95% CI, 12.7 to 21.5), and 14.7% (95% CI, 10.6 to 18.7), respectively.

[Spontaneous coronary dissection complicated by Takotsubo syndrome or Takotsubo syndrome complicated by spontaneous coronary dissection: the complex integration of invasive and non-invasive imaging]. / Dissezione coronarica spontanea complicata da sindrome Takotsubo o sindrome Takotsubo complicata da dissezione coronarica spontanea: quando l'integrazione tra imaging invasivo e non invasivo può essere complessa.

Spontaneous coronary artery dissection syndrome and Takotsubo syndrome are similar entities. They have peculiar features in common, such as a predilection for female sex, signs and symptoms compatible with acute coronary syndrome, high probability of restitutio ad integrum. The interdependence between these two diseases is of intriguing diagnostic and therapeutic implication.A 51-year-old woman presented to our attention with chest pain and evidence of ST-segment elevation. Coronary angiography showed the presence of type 2 dissection involving the diagonal branch. A conservative strategy was preferred. A severe emotional stress conditioned the following hours of hospitalization. A Takotsubo-like pattern was detected at focused echocardiogram. Cardiac magnetic resonance imaging confirmed the typical left ventricular motion abnormalities of a stress cardiomyopathy and T2-weighted sequences showed increased late gadolinium enhancement in the diagonal branch area, leading to the diagnosis of a concomitant coronary dissection and Takotsubo cardiomyopathy.

Adaptation and validation of the cardiovascular version of the Return-to-Work Obstacles and Self-Efficacy Scale (ROSES-CVD) to the Italian context.

PURPOSE: Effective cardiac rehabilitation interventions must provide adequate support to overcome psychosocial return-to-work (RTW) barriers. No validated instrument is available for this aim for cardiovascular patients. The Return-to-work Obstacles and Self-Efficacy Scale (ROSES) measures RTW obstacles workers perceive and the self-efficacy for overcoming them through 46 items and ten dimensions. This study aimed to adapt and validate ROSES for cardiovascular disease (CVD) in the Italian context. METHODS: This prospective study involved 183 CVD working patients at baseline and 121 six months later. ROSES-CVD internal consistency, construct, and predictive validity was evaluated with Cronbach's α, Confirmatory factor analyses (CFA), and ANCOVAs. RESULTS: CFAs adequately replicated the original ROSES model (CFI = .92-.96; TLI = .91-.94; RMSEA = .042-.057; SRMR = .046-.071) with α close or higher than .70 for all dimensions. Four ROSES-CVD dimensions significantly predicted the number of days to RTW controlling for age, gender, educational level, and surgery type. Workers who perceived salient RTW obstacles and low self-efficacy in any of these dimensions in mean returned to work from 38 to 53 days later. CONCLUSIONS: The study supported the validity and reliability of ROSES-CVD. This tool can be used in rehabilitation to detect CVD patients at risk of a longer RTW process and define appropriate cardiac rehabilitation intervention.IMPLICATIONS FOR REHABILITATIONVocational rehabilitation interventions should provide tailor-made support to overcome RTW barriers based on individual risk assessmentThe Italian translation of ROSES-CVD is a valid and reliable tool to measure psychosocial barriers to RTW among CVD working patientsThe use of ROSES-CVD would allow detection of CVD patients at risk of longer RTW processAdministering ROSES-CVD can help focus traditional vocational intervention on individually relevant obstacles to RTW.

Staged management of cardiac disease and concomitant early lung cancer: a 20-year single-center experience.

OBJECTIVES: The association of unstable heart disease and resectable lung cancer is rare. The impacts of staged management, cardiac surgery with cardiopulmonary bypass (CPB) versus angioplasty, on long-term survival and cancer recurrence remain debated. We report our experience using staged management. METHODS: From 1997 to 2016, 107 patients were treated at the Quebec Heart and Lung Institute: 72 underwent cardiac surgery with CPB (group 1), 35 were treated with angioplasty (group 2), followed by oncological pulmonary resection. RESULTS: Two postoperative deaths (3%) and 1 ischaemic heart complication (1%) were reported in group 1. One death (3%) was reported in group 2. Two-year overall survival was 82% (59/72) in group 1 and 80% (28/35) in group 2; 5-year overall survival was 62% (33/53) in group 1 and 63% (19/30) in group 2. Two-year disease-free survival in group 1 was 79% (57/72) and 77% (27/35) in group 2; 5-year disease-free survival was 58% (31/53) in group 1 and 60% (18/30) in group 2. The independent risk factors for death after thoracic surgery were transfusions (P = 0.004) and grade ≥3 complications (P = 0.034). Independent risk factors for recurrence included the cancer stage (P < 0.001) and, paradoxically, a shorter delay between cardiac and lung procedures (P = 0.031). CONCLUSIONS: When a staged management remains feasible after cardiac procedure, oncological outcomes of patients with cardiopathy and lung cancer are satisfactory. CPB does not seem to be deleterious. The delay between procedures should intuitively be as small as possible but not at the expense of good recovery after the cardiac procedure.

Kinetics of soluble mesothelin in patients with malignant pleural mesothelioma during treatment.

RATIONALE: Previous data suggested that serum levels of soluble mesothelin (SM) are related to tumor size and may have prognostic significance in malignant pleural mesothelioma (MPM). OBJECTIVES: We tested the hypothesis that this marker could also be useful for monitoring response to treatment. METHODS: Serial measurements of SM were determined in 40 patients diagnosed with MPM and subjected to gene-transfer therapy using intrapleural infusion of an adenoviral vector expressing human IFN-beta or conventional treatment (mainly chemotherapy). MEASUREMENTS AND MAIN RESULTS: In patients with baseline SM levels greater than 1 nM/L and disease progression after therapy, SM levels increased by 2.1 nM/L at two, 5.2 nM/L at four and 1.3 nM/L at 6 months. Patients with initial SM below 1 nM/L had a similar but more moderate increase of SM over time. Patients who responded to treatment or were considered stable had an initial small decrease of SM followed by a return to baseline values after 6 months of follow-up. In patients with baseline SM levels greater than 1 nM/L, increasing levels were associated with a significantly shorter median survival than in patients with stable or decreasing SM levels (4.4 vs. 27.7 months; P = 0.012). CONCLUSIONS: Increasing serum levels of SM were associated with disease progression and worse outcome, whereas stable or decreasing values suggested response to treatment. If confirmed in larger series, SM could be used to monitor patients with malignant pleural mesothelioma under treatment.

Heart rate detection with accelerometric sensors under the mattress.

The ballistocardiography is a technique that measures the heart rate from the mechanical vibrations of the body due to the heart movement. In this work a novel noninvasive device placed under the mattress of a bed estimates the heart rate using the ballistocardiography. Different algorithms for heart rate estimation have been developed.

Embedded system for non-obtrusive sleep apnea detection.

This document presents a new complete standalone system for a recognition of sleep apnea using signals from the pressure sensors placed under the mattress. The developed hardware part of the system is tuned to filter and to amplify the signal. Its software part performs more accurate signal filtering and identification of apnea events. The overall achieved accuracy of the recognition of apnea occurrence is 91%, with the average measured recognition delay of about 15 seconds, which confirms the suitability of the proposed method for future employment. The main aim of the presented approach is the support of the healthcare system with the cost-efficient tool for recognition of sleep apnea in the home environment.

Atypical Presentation of Aspergillus Mediastinitis Infection in a Heart Transplant Patient: the Importance of Combined Medical and Surgical Treatment.

Aspergillus fumigatus is an opportunistic fungus that mainly affects immunocompromised patients. Due to significant immunosuppressive therapy, patients who undergo orthotopic heart transplant have an increased risk of infection. Aspergillosis is the most common fungal infection in orthotopic heart transplant recipients (70%) and usually presents as invasive aspergillosis, which has a rapidly progressive course and is highly fatal. In heart transplant patients with invasive aspergillosis, overall mortality may range from 53% to 78%. Aspergillus mediastinitis infection is somewhat rare in orthotopic heart transplant recipients, with only 6 reported cases. Treatment may require early surgical drainage and antifungal therapy. We present the case of a 50-year-old man who developed Aspergillus mediastinitis 1 year after heart transplant surgery. This case illustrates the diagnostic challenge of an atypical presentation of Aspergillus mediastinitis and the importance of multiple drainage procedures in refractory disease, combined with long-term antifungal therapy.

Perioperative mortality and morbidity after sublobar versus lobar resection for early-stage non-small-cell lung cancer: post-hoc analysis of an international, randomised, phase 3 trial (CALGB/Alliance 140503).

BACKGROUND: Increased detection of small-sized, peripheral, non-small-cell lung cancer has renewed interest in sublobar resection instead of lobectomy, the traditional standard of care for early-stage lung cancer. We aimed to assess morbidity and mortality associated with lobar and sublobar resection for early-stage lung cancer. METHODS: CALGB/Alliance 140503 is a multicentre, international, non-inferiority, phase 3 trial in patients with peripheral non-small-cell lung cancer clinically staged as T1aN0. Patients were recruited from 69 academic and community-based institutions in Australia, Canada, and the USA. Patients were randomly assigned intraoperatively to either lobar or sublobar resection. The random assignment was based on permuted block randomisation without concealment and was stratified according to radiographic tumour size, histology, and smoking status. The primary endpoint of the trial is disease-free survival; here, we report a post-hoc, exploratory, comparative analysis of perioperative mortality and morbidity associated with lobar and sublobar resection. Perioperative mortality was defined as death from any cause within 30 days and 90 days of surgical intervention and was calculated for all randomised patients. Morbidity was graded using Common Terminology Criteria for Adverse Events version 4.0. All analyses were done on an intention-to-treat basis for randomised patients with data available. This trial is registered with ClinicalTrials.gov, number NCT00499330. FINDINGS: Between June 15, 2007, and March 13, 2017, 697 patients were randomly allocated to either lobar resection (n=357) or sublobar resection (n=340; 59% wedge resection). Six (0·9%) patients died by 30 days, four (1·1%) after lobar resection and two (0·6%) after sublobar resection; by 90 days, ten (1·4%) patients had died, six (1·7%) after lobar resection and four (1·2%) after sublobar resection (difference at 30 days, 0·5%, 95% CI -1·1 to 2·3; difference at 90 days, 0·5%, 95% CI -1·5 to 2·6). An adverse event of any grade occurred in 193 (54%) of 355 patients after lobar resection and 172 (51%) of 337 patients after sublobar resection. Adverse events of grade 3 or worse occurred in 54 (15%) patients assigned lobar resection and in 48 (14%) patients assigned sublobar resection. No differences between surgical approaches were noted in cardiac or pulmonary complications. Grade 3 haemorrhage (requiring transfusion) occurred in six (2%) patients assigned lobar resection and eight (2%) patients assigned sublobar resection. Prolonged air leak occurred in nine (3%) patients after lobar resection and two (1%) patients after sublobar resection. INTERPRETATION: Our post-hoc analysis showed that perioperative mortality and morbidity did not seem to differ between lobar and sublobar resection in physically and functionally fit patients with clinical T1aN0 non-small-cell lung cancer. These data may affect the daily choices made by patients and their doctors in establishing the best treatment approach for stage I lung cancer. FUNDING: National Cancer Institute.

Transcriptomic Microenvironment of Lung Adenocarcinoma.

Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

Management of postintubation tracheobronchial ruptures.

STUDY OBJECTIVES: To determine whether nonoperative management can be applied to iatrogenic postintubation tracheobronchial rupture (TBR). DESIGN: Prospective cohort study. PATIENTS AND INTERVENTIONS: Thirty consecutive patients with TBR complicating intubation between June 1993 and December 2005 entered the study. Patients not receiving mechanical ventilation at time of diagnosis were treated nonsurgically. Patients receiving mechanical ventilation who were judged operable underwent surgical repair, while nonoperable candidates had their TBR bridged by endotracheal tubes. RESULTS: Fifteen patients not requiring mechanical ventilation underwent simple conservative management. TBR length measured 3.85 +/- 1.46 cm (mean +/- SD). Eight TBRs showed full-thickness rupture with frank anterior intraluminal protrusion of the esophagus. In three patients, transient noninvasive positive pressure ventilatory support (NIV) was necessary. All lesions healed without sequelae. Two patients receiving mechanical ventilation underwent surgical repair and died. Thirteen patients receiving mechanical ventilation were considered at high surgical risk, and TBR bridging was attempted as salvage therapy. Complete bridging was achieved in five patients by simply advancing the endotracheal tube distal to the injury. Separate bilateral mainstem endobronchial intubation was necessary in six patients whose TBRs were too close to the carina. Nine of 13 patients (69%) treated with nonoperative therapy completely recovered. CONCLUSION: We conclude that conservative nonoperative therapy should be considered in patients with postintubation TBR who are breathing spontaneously, or when extubation is scheduled within 24 h from the time of diagnosis, or when continued ventilation is required to treat an underlying respiratory status. Surgical repair should be reserved for cases in which NIV or bridging the lesion is technically not feasible.