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Objective: To determine whether targeted sampling (TS), which omits biopsy of triple- normal lymph nodes (LNs) on positron emission tomography, computed tomography, and endobronchial ultrasound (EBUS), is noninferior to systematic sampling (SS) of mediastinal LNs during EBUS for staging of patients with early-stage non-small cell lung cancer (NSCLC)., Methods: Patients who are clinical nodal (cN)0-N1 with suspected NSCLC eligible for EBUS based on positron emission tomography/computed tomography were enrolled in this prospective, multicenter trial. During EBUS, all patients underwent TS and then crossed over to SS, whereby at least 3 mediastinal LN stations (4R, 4L, 7) were routinely sampled. Gold standard of comparison was pathologic results. Based on the previous feasibility trial, a noninferiority margin of 6% was established for difference in missed nodal metastasis (MNM) incidence between TS and SS. The McNemar test on paired proportions was used to determine MNM incidence for each sampling method. Analysis was per-protocol using a level of significance of P < .05., Results: Between November 2020 and April 2022, 91 patients were enrolled at 6 high-volume Canadian tertiary care centers. A total of 256 LNs underwent TS and SS. Incidence of MNM was 0.78% in SS and 2.34% in TS, with an absolute difference of 1.56% (95% confidence interval, -0.003% to 4.1%; P = .13). This falls within the noninferiority margin. A total of 6/256 LNs from 4 patients who were not sampled by TS were found to be malignant when sampled by SS., Conclusions: In high-volume thoracic endosonography centers, TS is not inferior to SS in nodal staging of early-stage NSCLC. This results in change of clinical management for a minority of patients., Competing Interests: Conflict of Interest Statement Dr Turner serves on an advisory board and has received speaker honoraria from Astra Zeneca. Dr Yasufuku has received unrestricted grants from Olympus Medical Systems for continuing medical education. Dr Hanna serves on an advisory board for AstraZeneca, data safety committee for Roche/Genentech, and speaker’s bureau for Minogue Medical. Dr Nayak has received speaker honoraria from Merck and Co. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Triple normal lymph nodes, appearing benign on computed tomography, positron emission tomography, and endobronchial ultrasound, have less than a 6% probability of malignancy. We hypothesized that targeted sampling (TS), which omits biopsy of triple normal lymph nodes during endobronchial ultrasound, is not an inferior staging strategy to systematic sampling (SS) of all lymph nodes., Methods: A prospective randomized feasibility trial was conducted to decide on the progression to a pan-Canadian trial comparing TS with SS. Patients with cN0-N1 non-small cell lung cancer undergoing endobronchial ultrasound were randomized to TS or SS. Lymph nodes in the TS arm crossed over to receive SS. Progression criteria included recruitment rate (70% minimum), procedure length (no significant increase for TS), and incidence of missed nodal metastasis (<6%). Mann-Whitney U test and McNemar's test on paired proportions were used for statistical comparisons., Results: The progression criterion of 70% recruitment rate was achieved early, triggering a planned early stoppage of the trial. Nineteen patients were allocated to each arm. The median procedure length for TS was significantly shorter than SS (3.07 vs 19.07 minutes; P < .001). After crossover analysis, 5.45% (95% confidence interval, 1.87-14.85) of lymph nodes in the TS arm were upstaged from N0 to N2, but this incidence of missed nodal metastasis was below the 6% threshold. During surgical resection, the nodal upstaging incidence from N0 to N2 was 0% for 15 lymph nodes in each arm., Conclusions: Progression criteria to a pan-Canadian, noninferiority crossover trial comparing TS with SS have been met, and such a trial is warranted., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Thoracic surgery is associated with significant rates of postoperative morbidity and postdischarge return to the hospital or emergency department (ED). This study aims to assess the impact of a novel integrated patient-centered, hospital-based multidisciplinary community program (Integrated Comprehensive Care [ICC]) on postdischarge outcomes in patients undergoing thoracic surgery compared to routine care., Methods: This was a retrospective cohort study of patients who underwent surgical resection for lung malignancies at a tertiary care center from 2010 to 2014. Patients were divided into 2 cohorts based on their enrollment in the ICC program (intervention cohort; 2012-2014) or routine postoperative care (control cohort; 2010-2012). Propensity score matching was performed to match the 2 cohorts. The impact of the ICC program on postoperative length of stay (LOS), rate of ED visits, readmissions, and mortality within the first 60 days was assessed., Results: Of the 1288 patients included in this study, 658 (51.1%) were male patients with mean age of 64 years (standard deviation 14.1 years). After propensity score matching, 478 patients were enrolled in the ICC cohort and 592 were enrolled as controls. The ICC cohort had significantly shorter LOS (4 days, vs 5 days in controls, P = .001), lower rate of 60-day ED visits (9.8% vs 28.4% in controls, P < .001), and readmissions (6.9% vs 8.6% in controls, P < .001). The 60-day mortality was also significantly lower in the ICC cohort compared with the control group (0.6% vs 0.8% in controls, P < .001)., Conclusions: The ICC program is associated with shorter LOS, fewer ED visits and readmissions after discharge, and ultimately may decrease postoperative mortality., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective(s): During endobronchial ultrasound (EBUS) staging, ultrasonographic features can be used to predict mediastinal lymph node (LN) malignancy. We sought to develop the Canada Lymph Node Score a tool capable of predicting LN metastasis at the time of EBUS., Methods: Patients undergoing EBUS staging for lung and esophageal cancer were prospectively enrolled. Features were identified in real time by an endoscopist and video-recorded. Videos were sent to raters. Pathologic specimens from biopsies/surgical resections were used as the gold-standard reference test. Logistic regression, receiver operator characteristic curve, and Gwet's AC1 analyses were used to test the performance, discrimination, and inter-rater reliability, respectively., Results: In total, 300 LNs from 140 patients were analyzed by 12 endoscopists (raters) across 7 Canadian centers. Beta-coefficients from a multivariate regression model were used to create a 4-point score: short-axis diameter, margins, central hilar structure, and necrosis. The model showed good discriminatory power (c-statistic = 0.72 ± 0.04, 95% confidence interval [CI], 0.64-0.80; bias-corrected c-statistic: 0.66, 95% CI, 0.55-0.76). LNs scoring 3/4 or 4/4 had odds ratios of 15.17 (P < .0001) and 50.56 (P = .001) for predicting malignancy, respectively. Inter-rater reliability for a score ≥3 was 0.81 ± 0.02 (95% CI, 0.77-0.85)., Conclusions: The Canada Lymph Node Score is a 4-point score demonstrating excellent performance in identifying malignant LNs during EBUS. A cut-off of ≥3 may inform decision-making regarding biopsy, repeat biopsy, or mediastinoscopy if the initial results are inconclusive., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Near-infrared fluorescence mapping with indocyanine green dye is a recent advancement in minimally invasive segmental resection. This technique has not yet been reproduced, validated, or objectively evaluated in a large prospective case series. We hypothesized that near-infrared fluorescence mapping is associated with an increased oncological margin distance from the tumor, over and above the best judgment of the surgeon., Methods: This was a phase 2 prospective cohort trial in patients who are undergoing robotic segmentectomy for lung tumors <3 cm. The predicted intersegmental plane was first identified by consensus between 2 thoracic surgeons. The true plane was then mapped by indocyanine green injection. A 7-item binary rating scale was used for the evaluation of feasibility, reproducibility, and added oncological margin distance from the tumor. The margin distance between the tumor and the true plane was compared with the margin distance between the tumor and the predicted plane., Results: Fifty-three patients were enrolled between September 2016 and May 2018 and 31 patients (58.4%) received the planned operation with indocyanine green mapping. In 74.2% of cases (23 out of 31), a score of 7 out of 7 was achieved, indicating the true intersegmental plane identified by indocyanine green mapping was different than the predicted plane identified by the surgeon. In 61.2% (19 out of 31) of those cases, the mean additional margin distance from the tumor to the staple line attributable to the indocyanine green mapping was 2.41 ± 1.6 cm. The overall complication rate was 18.5% (10 out of 53) and there were no deaths., Conclusions: Near-infrared fluorescence mapping in robotic segmentectomy is associated with increased oncological margin length, over and above the best judgment of the surgeon, in the majority cases where it is used., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine the frequency, characteristics, and survival of second primary lung cancer initially identified as an indeterminate lesion on the original computed tomography scan and then diagnosed during the surveillance period in a prospective study., Methods: A prospective database of 271 patients enrolled in a surveillance study was updated. Indeterminate lesions present on the original computed tomography at the time of initial primary lung cancer diagnosis that subsequently grew and were diagnosed as cancer were termed "synchronous primary lung cancer." Lesions that were not present on the original computed tomography scan and subsequently diagnosed on surveillance were termed "metachronous primary lung cancer.", Results: Thirty patients (11.1%) developed 37 second primary lung cancers over a median surveillance period of 84.7 (range, 15.9-147.6) months. Of these, 15 of 37 (40.5%) were identified as synchronous primary lung cancer, and 22 of 37 (59.5%) were identified as metachronous primary lung cancer. At first identification, ground-glass lesions were identified in 9 of 15 (60%) synchronous primary lung cancers compared with only 5 of 22 (22.7%) of metachronous primary lung cancers (P = .034). Compared with metachronous primary lung cancer, from first identification to diagnosis, synchronous primary lung cancer developed over a longer interval (33.6 vs 7.2 months, P = .001) and had a slower growth rate (0.17 vs 0.45 mm/month, P = .027). The 5-year overall survival from second lung cancer was 73.0%. No significant differences were observed between the synchronous primary lung cancer and metachronous primary lung cancer cohorts in overall survival from initial primary lung cancer (P = .583) or from second lung cancer (P = .966)., Conclusions: Computed tomography surveillance identifies 2 types of curable second lung cancers leading to excellent overall survival., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the prevalence of delayed postoperative venous thromboembolism (VTE) in patients undergoing oncologic lung resections, despite adherence to current in-hospital VTE prophylaxis guidelines., Methods: Patients undergoing lung resection for malignancy in 2 tertiary-care centers were recruited between June 2013 and December 2014. All patients received guideline-based VTE prophylaxis until hospital discharge. Patients underwent computed tomography chest angiography with pulmonary embolism (PE) protocol and bilateral lower extremity venous Doppler ultrasonography at 30 ± 5 days after surgery to determine the incidence of postoperative VTE. Univariate analysis was used to compare the VTE and non-VTE groups., Results: A total of 157 patients were included, 45.9% were men with a mean age of 66.7 years. VTE prevalence was 12.1% with a total of 19 VTE events, including 14 PEs (8.9%), 3 deep venous thromboses (DVTs) (1.9%), 1 combined PE/DVT, and 1 massive left atrial thrombus originating from the pulmonary vein stump after pulmonary lobectomy. PE events occurred in the operated lung 64% of the time and 4 patients (21.1%) were symptomatic at diagnosis. The 30-day mortality rate of VTE events was 5.2%, with 1 patient who died secondary to massive in situ ipsilateral PE following readmission to the hospital. Univariate analysis did not demonstrate significant differences between the VTE and non-VTE populations with regard to baseline characteristics., Conclusions: Despite adherence to in-hospital standard prophylaxis guidelines, VTE events are frequent, often asymptomatic, and with associated significant morbidity and mortality. More research into the potential role of predischarge screening and extended prophylaxis is warranted., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: A minimal-dose computed tomography scan of the thorax (MnDCT) delivers a radiation dose comparable with a chest x-ray (CXR). We hypothesized that in patients with completely resected lung cancer, surveillance with MnDCT, when compared with CXR, leads to earlier detection and a higher rate of treatment of new or recurrent lung cancer., Methods: After lung cancer resection, patients prospectively were enrolled for surveillance with MnDCT and CXR at 3, 6, 12, 18, 24, 36, 48, and 60 months. Images were interpreted by different blinded radiologists. When new or recurrent cancer was suspected, standard-dose CT and/or a tissue biopsy were performed for confirmation., Results: Between 2007 and 2012, 271 patients were included and 1137 pairs of CXR and MnDCT were analyzed. MnDCT was more sensitive (94% vs 21%; P < .0001) and had a higher negative predictive value (99% vs 96%; P = .007) than CXR for the diagnosis of new or recurrent lung cancer. The prevalence of new or recurrent lung cancer was 23.2% (63 of 271), of whom 78% (49 of 63) had asymptomatic disease. The majority of asymptomatic patients (75%; 37 of 49) were treated with curative intent and had a median survival of 69 months. The remainder of patients received palliative treatment (24%; 12 of 49) and had a median survival of 25 months (P < .0001)., Conclusions: After curative resection of lung cancer, MnDCT is superior to CXR for the detection of new or recurrent lung cancer. The majority of new or recurrent cancer was detected by MnDCT at an asymptomatic phase, allowing for curative treatment, leading to a long survival., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)