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Introduction: Annual low-dose computed tomography (LDCT) screening has been shown to reduce lung cancer mortality in high-risk individuals by detecting the disease at an earlier stage. This study aims to assess the barriers to completing LDCT in a cohort of patients who were determined eligible for lung cancer screening (LCS)., Methods: We performed a single institution, mixed methods, cross-sectional study of patients who had a LDCT ordered from July to December 2022. We then completed phone surveys with patients who did not complete LDCT to assess knowledge, attitude, and perceptions toward LCS., Results: We identified 380 patients who met inclusion criteria, including 331 (87%) who completed LDCT and 49 (13%) who did not. Patients who completed a LDCT and those who did not were similar regarding age, sex, race, primary language, household income, body mass index, median pack years, and quit time. Positive predictors of LDCT completion were: meeting USPSTF guidelines (97.9% vs 81.6%), being married (58.3% vs 44.9%), former versus current smokers (55% vs 41.7%), personal history of emphysema (60.4% vs 42.9%), and family history of lung cancer (13.9% vs 4.1%) (all P < .05). Of the patients who participated in the phone survey, only 7% of respondents thought they were high risk for developing lung cancer despite attending a shared decision-making visit and only 10% wanted to re-schedule their LDCT., Conclusion: There exist barriers to completing LDCT even after patients are identified as eligible and complete a shared decision-making visit secondary to knowledge barriers, misperceptions, and patient disinterest., Competing Interests: Disclosure The authors have no conflicts of interest or funding sources related to this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Sublobar resection of early-stage non-small cell lung cancer (NSCLC) is increasingly considered appropriate but may compromise margins compared with lobectomy. This study evaluated resection extent, margin status, and survival in patients with clinical stage I NSCLC., Methods: Patients with clinical T1-2 N0 M0 NSCLC in the National Cancer Database (2006-2020) who were treated with primary surgery were compared stratified by margin status. The potential benefit of radiation was explored in subgroup analysis of patients who underwent sublobar resection with positive margins., Results: Positive margins occurred in 5089 (2.8%) of 181,824 patients and were more common in sublobar resections compared with lobectomy (4.3% vs 2.4%; P < .001). Sublobar resection had the strongest association with positive margins in multivariable analysis (odds ratio, 2.06; 95% CI, 1.91-2.23; P < .001). Patients with positive margins were more likely to undergo both adjuvant chemotherapy (16% vs 13%; P < .001) and radiation (17% vs 1%; P < .001) but had worse survival in univariate analysis (44.0% 5-year overall survival vs 69.2%; P < .001) and multivariable Cox analysis (hazard ratio, 1.71; 95% CI, 1.63-1.78; P < .001) in the entire cohort, as well as in a univariate subset analysis of lobectomy (46.9% vs 70.4%; P < .001) and sublobar resection (37.5% vs 64.1%; P < .001). Postoperative radiation for patients who underwent sublobar resection with positive margins did not improve 5-year overall survival (36.3% for irradiated patients vs 38.3% for nonirradiated patients; P = .57), and patients who underwent sublobar resection with positive margins who were treated with radiation had survival inferior to that of patients who underwent lobectomy with negative margins., Conclusions: Positive margins occur more frequently after sublobar resection of clinical stage I NSCLC compared with lobectomy. Patients with positive margins have worse survival than patients who undergo complete resection and are not rescued by postoperative radiation., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Sublobar resection offers noninferior survival vs lobectomy for ≤2 cm non-small cell lung cancer and is commonly used for subsolid tumors. Although data exist for solid tumors, the minimum adequate margin of resection for subsolid adenocarcinomas remains unclear., Methods: This was a retrospective review of 1101 adenocarcinoma resections at our institution from 2006 to 2022. Inclusion criteria were tumors ≤3 cm with ≥10% radiographic ground glass, excised by sublobar resection. Exclusions were positive nodes or positive or unreported margin. The primary outcome was the rate of local recurrence (LR) at multiple thresholds of margin distance. The relationship between margin distance and solid component size was also explored., Results: Inclusion criteria were met by 194 patients. Median (interquartile range) tumor diameter and margin distance were 12 mm (9-17 mm) and 10 mm (5-17 mm), respectively. Median follow-up was 42.5 months. There was a progressive increase in LR with diminishing margin (0.1-cm decrements) from 1.5 cm to 0.5 cm. The difference in the rate of LR between "over" (n = 143) and "under" (n = 51) was most significant at 0.5 cm (8 of 51 [15.7%] vs 6 of 143 [4.2%]; P = .01) but did not reach α adjusted for multiple comparisons. On Cox regression for LR-free survival, margin ≤0.5 cm (P = .19) and solid component percentage (P = .14) trended to significance. Combining these using a ratio of margin distance-to-solid component size, a ratio of ≤1 showed a significantly higher rate of LR (7 [14.3%] vs 2 [2.0%], P = .009). Treatment of LRs provided at least intermediate-term survival in 87% of recurrences (median postrecurrence follow-up was 44 months)., Conclusions: During sublobar resection of subsolid lung adenocarcinomas, a margin distance-to-solid component size ratio of >1.0 appears to be a more reliable factor than margin distance alone to minimize local recurrence. Local recurrence, however, may not impact survival in patients with subsolid adenocarcinomas if timely treatment is administered., Competing Interests: Disclosures Joseph Shrager reports a relationship with Merck & Co Inc that includes: consulting or advisory; with Becton Dickinson and Company that includes: consulting or advisory; and with Varian Medical Systems Inc that includes: funding grants. Leah Backhus reports a relationship with Johnson and Johnson that includes: consulting or advisory; with Bristol-Myers Squibb Co that includes: consulting or advisory; with AstraZeneca that includes: consulting or advisory; and with Genentech that includes: consulting or advisory. Natalie Lui reports a relationship with Intuitive Surgical Inc that includes: consulting or advisory and with Centese that includes: consulting or advisory. The other authors have no conflicts of interest to disclose., (Published by Elsevier Inc.)

Competing Interests: Disclosures Sukhmani K. Padda reports a relationship with Takeda, AstraZeneca, Bayer, Amgen, Sanofi Genzyme, Rayze Biotech, Mirati, Janssen, Regeneron, Jazz Pharma, Genentech, Nanobiotix, G1 Therapeutics, Blueprint, Pfizer, and Abbvie that includes: advisory board/consulting; with PER, Curio Science LLC, MECC Global Meetings, and CME Solutions that includes: CME; and with EpicentRx, Bayer, Boehringer-Ingelheim, Bioalta, Takeda, and Amgen that includes: research (paid to institution). The other authors have no conflicts of interest to disclose.

Background: Lepidic-type adenocarcinomas (LPAs) can be multifocal, and treatment is often deferred until growth is observed. This study investigated the potential downside of that strategy by evaluating the relationship of nodal involvement with tumor size and survival., Methods: The impact of tumor size on lymph node involvement and survival was evaluated for National Cancer Database patients who underwent surgery without induction therapy as primary treatment for cT1-3 N0 M0 histologically confirmed LPA from 2006 to 2019 by using logistic regression, Kaplan-Meier, and Cox analyses., Results: Positive nodes occurred in 442 of 8286 patients (5.3%). The incidence of having positive nodes approximately doubled with each 1-cm increment increase in size. Patients with positive nodes were more likely to have larger tumors (27 mm vs 20 mm, P < .001) and clinical ≥T2 disease (40.7% vs 26.8%, P < .001) compared with node-negative patients. However, tumor size was the only significant independent predictor of having positive nodal disease in logistic regression analysis, and this association grew stronger with each incremental centimeter increase in size. Patients with positive nodes were more likely to undergo adjuvant radiotherapy (23.5% vs 1.1%, P < .001) and chemotherapy (72.9% vs 7.9%, P < .001), and expectedly, had worse survival compared with the node-negative group in univariate (5-year overall survival, 50.9% vs 81.1%, P < .001) and multivariable (hazard ratio, 2.56; 95% CI, 2.14-3.05; P < .001) analyses., Conclusions: Nodal involvement is relatively uncommon in early-stage LPAs but steadily increases with tumor size and is associated with dramatically worse survival. These data can be used to inform treatment decisions when evaluating LPA patients., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Incidental pulmonary nodules are common. Although the majority are benign, most are indeterminate for malignancy when first encountered making their management challenging. CT remains the primary imaging modality to first characterize and follow-up incidental lung nodules. This document reviews available literature on various imaging modalities and summarizes management of indeterminate pulmonary nodules detected incidentally. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: This study evaluated outcomes of patients who undergo extended delay to resection after definitive radiation therapy for non-small cell lung cancer (NSCLC)., Methods: Perioperative outcomes and 5-year overall survival of patients with NSCLC who underwent definitive radiation therapy, followed by resection, from 2004 to 2020 in the National Cancer Database were evaluated. Patients who underwent resection >180 days after the initiation of radiation therapy (including any external beam therapy at a total dose of >60 Gy) were included in the analysis. Subgroup analyses were conducted by operation type and pathologic nodal status., Results: From 2004 to 2020, 293 patients had an extended delay to resection after definitive radiation therapy. The clinical stage distribution was stage I to II in 53 patients (18.1%), stage IIIA in 111 (37.9%), stage IIIB in 106 (36.2%), stage IIIC in 13 (4.4%), and stage IV in 10 (3.4%). Median dose of radiation therapy received was 64.8 Gy (interquartile range, 60.0-66.6 Gy). Median days from radiation therapy to resection were 221.0 (interquartile range, 193.0-287.0) days. Lobectomy (64.5%) was the most common operation, followed by pneumonectomy (17.1%) and wedge resection (7.5%). For wedge resection, lobectomy, and pneumonectomy, the 30-day readmission rate was 4.8%, 4.8%, and 8.3%, the 30-day mortality rate was 0%, 3.4%, and 6.4%, and the 90-day mortality rate was 0%, 6.2%, and 12.8%, respectively. Overall survival at 5 years for patients with pN0, pN1, and pN2 disease was 38.6% (95% CI, 30.0-47.2), 43.3% (95% CI, 16.3-67.9), and 24.0% (95% CI, 9.8-41.7), respectively., Conclusions: In this national analysis, extended delay to resection after definitive radiation therapy was associated with acceptable perioperative outcomes among a highly selected patient cohort., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: This joint guideline by American Society for Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) was initiated to review evidence and provide recommendations regarding the use of local therapy in the management of extracranial oligometastatic non-small cell lung cancer (NSCLC). Local therapy is defined as the comprehensive treatment of all known cancer-primary tumor, regional nodal metastases, and metastases-with definitive intent., Methods: ASTRO and ESTRO convened a task force to address 5 key questions focused on the use of local (radiation, surgery, other ablative methods) and systemic therapy in the management of oligometastatic NSCLC. The questions address clinical scenarios for using local therapy, sequencing and timing when integrating local with systemic therapies, radiation techniques critical for oligometastatic disease targeting and treatment delivery, and the role of local therapy for oligoprogression or recurrent disease. Recommendations were based on a systematic literature review and created using ASTRO guidelines methodology., Results: Based on the lack of significant randomized phase 3 trials, a patient-centered, multidisciplinary approach was strongly recommended for all decision-making regarding potential treatment. Integration of definitive local therapy was only relevant if technically feasible and clinically safe to all disease sites, defined as 5 or fewer distinct sites. Conditional recommendations were given for definitive local therapies in synchronous, metachronous, oligopersistent, and oligoprogressive conditions for extracranial disease. Radiation and surgery were the only primary definitive local therapy modalities recommended for use in the management of patients with oligometastatic disease, with indications provided for choosing one over the other. Sequencing recommendations were provided for systemic and local therapy integration. Finally, multiple recommendations were provided for the optimal technical use of hypofractionated radiation or stereotactic body radiation therapy as definitive local therapy, including dose and fractionation., Conclusions: Presently, data regarding clinical benefits of local therapy on overall and other survival outcomes is still sparse for oligometastatic NSCLC. However, with rapidly evolving data being generated supporting local therapy in oligometastatic NSCLC, this guideline attempted to frame recommendations as a function of the quality of data available to make decisions in a multidisciplinary approach incorporating patient goals and tolerances., Competing Interests: Disclosures All task force members’ disclosure statements were reviewed before being invited and were shared with other task force members throughout the guideline's development. Those disclosures are published within this guideline. Where potential conflicts were detected, remedial measures to address them were taken. Tom Boike: APEx reviewer (honoraria), Boston Scientific (speaker's bureau); Anne-Marie Dingemans: Amgen (advisory board, research), Bayer, Boehringer Ingelheim, Lilly, PharmaMar, Roche, Sanofi (all advisory boards), AstraZeneca, Chiesi, Janssen, Pfizer, Takeda (all honoraria), EORTC Lung Cancer Group (chair); Jill Feldman (patient representative): AstraZeneca, Blueprint Medicines, Janssen, Novartis (all honoraria), EGFR Resisters (cofounder), IASLC Patient Advocate Committee (chair); Daniel Gomez: AstraZeneca (consultant and research), GRAIL (consultant), Johnson & Johnson (consultant), Medtronic (advisory board), Medical Learning Group (honoraria–ended 8/2021), Varian (consultant and research); Matthias Guckenberger (co-chair): European Thoracic Oncology Platform (research), Varian (research-ended 12/2020), ViewRay (institutional research), ESTRO (president); Paul Hesketh (American Society of Clinical Oncology representative): UpToDate (consultant – editor); Puneeth Iyengar (co-chair): AstraZeneca (advisory board-ended 12/2020), National Cancer Institute/NRG Oncology (research – PI); Salma Jabbour: Advarra (consultant – DSMB), IMX Medical and Merck (consultant), Novocure (consultant-ended 4/2022), Beigene and Merck (institutional research grant), Syntactx (consultant – adjudication committee), International Journal of Radiation Oncology, Biology, and Physics (deputy editor), NCI Radiation Research Program, Upper GI Work Group (co-chair); Mirjana Josipovic: Danish National Research Center for Radiation Therapy (research), Varian (institutional research); Yolande Lievens: AstraZeneca (institutional research), Belgium College for Physicians in Radiation Oncology, (deputy chair-ended 10/2021), Belgium College of Oncology & AntiCancer Fund (board member), European Cancer Organization (Ex-officio executive committee member-ended 3/2022), ESTRO (former president), UGent Chair on ESTRO value-based health care (promotor, institutional research); Fiona McDonald: AstraZeneca (institutional research), Cancer Research United Kingdom (research – PI), Merck (institutional research), IASLC Advanced Radiotherapy Committee (chair), ESTRO ACROP Guidelines Committee (chair), UK SABR Consortium (chair); Bradford Perez: BMS (consultant, research-ended 12/2021), G1 Therapeutics (consultant–ended 4/2021); Umberto Ricardi: BrainLab (institutional research), ESTRO (past president); Enrico Ruffini: AstraZeneca (honoraria), European Society of Thoracic Surgeons (past president), IASLC (steering committee and chair, Thymic subcommittee); Dirk De Ruysscher: AstraZeneca and BMS (research and institutional advisory board), BeiGene (institutional research), Celgene, Merck/Pfizer, Roche/Genentech, Seattle Genetics (all institutional advisory boards), EORTC Lung Oligometastases committee (chair); Suresh Senan: AstraZeneca (advisory board – DSMB), BMS (consultant–ended 6/2022), BeiGene (advisory board-ended 3/2021), Merck (consultant), Varian and ViewRay (institutional research); Joachim Widder: Elekta and Raysearch (institutional research); Hina Saeed (Guideline Subcommittee representative),Clinical and Translational Radiation Oncology (editor); Bryan Schneider (American Society of Clinical Oncology representative), ASCO Guideline advisory group (co-chair), NCCN Immune Checkpoint Inhibitor-Related Toxicities guideline (vice chair). Sean All, Mark Berry, and Lisa Bradfield reported no disclosures., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Observation of paraesophageal hernias (PEHs) may lead to emergent surgery for hernia-related complications. This study evaluated urgent or emergent repair outcomes to quantify the possible sequelae of failed conservative PEH management., Methods: The impact of operative status (elective vs urgent or emergent) on perioperative mortality or major morbidity for patients who underwent hiatal hernia repair for a PEH diagnosis from 2012 to 2021 in the Society of Thoracic Surgery General Thoracic Surgery Database was evaluated with multivariable logistic regression models., Results: Overall, 2082 (10.9%) of 19,122 patients with PEHs underwent urgent or emergent repair. Patients undergoing nonelective surgery were significantly older than patients undergoing elective surgery (median age, 73 years [interquartile range, 63-82 years] vs 66 years [interquartile range, 58-74 years]) and had a lower preoperative performance score (P < .001). Nonelective surgical procedures were more likely to be performed through the chest or by laparotomy rather than by laparoscopy (20% vs 11.4%; P < .001), and they were associated with longer hospitalizations (4 days vs 2 days; P < .001), higher operative mortality (4.5% vs 0.6%; P < .001), and higher major morbidity (27% vs 5.5%; P < .001). Nonelective surgery was a significant independent predictor of major morbidity in multivariable analysis (odds ratio, 2.06; P < .001). Patients more than the age of 80 years had higher operative mortality (4.3% vs 0.6%; P < 0.001) and major morbidity (19% vs 6.1%; P < .001) than younger patients overall, and these older patients more often had nonelective surgery (26% vs 8.6%; P < .001) CONCLUSIONS: The operative morbidity of PEH repair is significantly increased when surgery is nonelective, particularly for older patients. These results can inform the potential consequences of choosing watchful waiting vs elective PEH repair., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The role of cancer-directed surgery in the treatment of stage I-IIIA malignant pleural mesothelioma (MPM) by histologic subtypes remains controversial. The objective of this study was to evaluate the survival of the different histologic subtypes for stage I-IIIA MPM stratified by cancer-directed surgery and nonoperative management., Research Question: How is the histologic subtype, clinical stage, and use of cancer-directed surgery for MPM associated with overall survival?, Study Design and Methods: Overall survival of patients with stage I-IIIA epithelioid, sarcomatoid, and biphasic MPM in the National Cancer Database from 2004 through 2017 who underwent cancer-directed surgery (ie, surgery with or without chemotherapy or radiation) or chemotherapy with or without radiation (nonoperative management) was evaluated using Kaplan-Meier analysis, multivariable Cox proportional hazards analysis, and propensity score-matched analysis., Results: Of 2,285 patients with stage I-IIIA MPM who met inclusion criteria, histologic subtype was epithelioid in 71% of patients, sarcomatoid in 12% of patients, and biphasic in 17% of patients. Median survival was 20 months in the epithelioid group, 8 months in the sarcomatoid group, and 13 months in the biphasic group (P < .01). Among patients who underwent surgery, median survival was 25 months in the epithelioid group, 8 months in the sarcomatoid group, and 15 months in the biphasic group (P < .01). In multivariable Cox proportional hazards analyses, surgery was associated with improved survival in the epithelioid group (P < .01) but not in the sarcomatoid (P = .63) or biphasic (P = .21) groups. These findings were consistent in propensity score-matched analyses for each MPM histologic type., Interpretation: In this national analysis, cancer-directed surgery was found to be associated with improved survival for stage I-IIIA epithelioid MPM, but not for biphasic or sarcomatoid MPM., (Copyright © 2022 American College of Chest Physicians. All rights reserved.)

Background: The sensitivity of fluoroscopic esophagography with oral administration of contrast material to exclude anastomotic leak after esophagectomy is not well documented, and the consequences of missing a leak in this setting have not been previously described., Methods: We performed a retrospective cohort study of a prospectively maintained institutional database of patients undergoing esophagectomy with esophagogastric anastomosis from 2008 to 2020. Relevant details of leaks, management, and outcomes were obtained from the database and formal chart review. Statistical analysis was performed to compare patients with and without leaks and those with false-negative vs positive esophagrams., Results: There were 384 patients who underwent esophagectomy with gastric reconstruction; the majority were Ivor-Lewis (82%), and 51% were wholly or partially minimally invasive. By use of a broad definition of leak, 55 patients (16.7%) developed an anastomotic leak. Of the 55 patients, 27 (49%) who ultimately were found to have a leak initially had a normal esophagram result (performed on average on postoperative day 6). Those with a normal initial esophagram result were more likely to have an uncontained leak (81% vs 29%; P < .01), to require unplanned readmission (70% vs 39%; P = .02), and to undergo reoperation (44% vs 11%; P < .01)., Conclusions: Early postoperative esophagrams intended to evaluate anastomotic integrity have a low sensitivity of 51%, and leaks missed on the initial esophagram have greater clinical consequences than those identified on the initial esophagram. These findings suggest that a high index of suspicion must be maintained even after a normal esophagram result and call into question the common practice of using this test to triage patients for diet advancement., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Despite demonstration of its clear benefits relative to open approaches, a video-assisted thoracic surgery technique for pulmonary lobectomy has not been universally adopted. This study aims to overcome potential barriers by establishing the essential components of the operation and determining which steps are most useful for simulation training., Methods: After randomly selecting experienced thoracic surgeons to participate, an initial list of components to a lower lobectomy was distributed. Feedback was provided by the participants, and modifications were made based on anonymous responses in a Delphi process. Components were declared essential once at least 80% of participants came to an agreement. The steps were then rated based on cognitive and technical difficulty followed by listing the components most appropriate for simulation., Results: After 3 rounds of voting 18 components were identified as essential to performance of a video-assisted thoracic surgery for lower lobectomy. The components deemed the most difficult were isolation and division of the basilar and superior segmental branches of the pulmonary artery, isolation and division of the lower lobe bronchus, and dissection of lymphovascular tissue to expose the target bronchus. The steps determined to be most amenable for simulation were isolation and division of the branches of the pulmonary artery, the lower lobe bronchus, and the inferior pulmonary vein., Conclusions: Using a Delphi process a list of essential components for a video-assisted thoracic surgery for lower lobectomy was established. Furthermore 3 components were identified as most appropriate for simulation-based training, providing insights for future simulation development., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The eighth edition of the staging manual for non-small cell lung cancer reclassified tumors >7 cm as stage IIIA (T4 N0); previously, such tumors without nodal disease were considered stage IIB (T3 N0). This study tested the hypothesis that induction chemotherapy for these stage IIIA patients does not improve survival compared with primary surgery., Methods: The National Cancer Database was queried for patients with non-small cell lung cancer with tumor size >7 cm who underwent surgical resection from 2010 to 2015. Patients with clinically node-positive disease or tumor invasion of major structures were excluded. Patients undergoing induction chemotherapy followed by surgical resection (IC group) were compared with patients undergoing primary surgery (PS group). Propensity score matching was performed., Results: In total, 1610 patients with cT4 N0 disease on the basis of tumor size >7 cm and no tumor invasion underwent surgical resection: 1346 (83.6%) comprised the PS group and 264 (16.4%) the IC group. After propensity score matching, the IC group had a higher rate of pN0 (78.4% vs 66.0%; P < .001) and less lymphovascular invasion (13.9% vs 26.3%; P < .001), but longer postoperative stays (6 days vs 5 days; P < .001) and higher 30-day mortality (3.5% vs 0%; P = .002). Median 5-year survival was similar between the IC and PS groups (53.5% vs 62.2%; P = .075), and IC was not independently associated with survival (hazard ratio, 1.45; P = .146)., Conclusions: Patients with cT4 N0 non-small cell lung cancer on the basis of tumor size >7 cm and no tumor invasion of major structures have similar overall survival with either induction chemotherapy or primary surgery. Induction chemotherapy should not be routinely given for this subset of stage IIIA patients., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Enhanced recovery after surgery pathways in several specialties reduce length of stay, but accelerated discharge after thoracic surgery is not well characterized. This study tested the hypothesis that patients discharged on postoperative day 1 (POD1) after lobectomy for lung cancer have an increased risk of readmission., Methods: Patients who underwent a lobectomy for lung cancer between 2011 and 2019 in the American College of Surgeons National Surgical Quality Improvement Program database were identified. Readmission rates were compared between patients discharged on postoperative day 1 (POD 1) and patients discharged on POD 2 to 6. Early discharge and readmission predictors were evaluated using multivariable logistic regression analysis., Results: Only 854 (3.8%) of 22,585 patients who met inclusion criteria were discharged on POD 1, although POD 1 discharge rates increased from 2.3% to 8.1% (P < .001) from 2011 to 2019, respectively. Median hospitalization for patients discharged on POD 2 to 6 was 4 days (interquartile range, 3 to 5 days). Patients' characteristics associated with a lower likelihood of POD 1 discharge were increasing age, smoking, or a history of dyspnea, whereas a minimally invasive approach was the strongest predictor of early discharge (adjusted odds ratio, 5.42; P < .001). Readmission rates were not significantly different for the POD 1 and POD 2 to 6 groups in univariate analysis (6.0% vs 7.0%; P = .269). Further, POD 1 discharge was not a risk factor for readmission in multivariable analysis (adjusted odds ratio, 1.10; P = .537)., Conclusions: Select patients can be discharged on POD 1 after lobectomy for lung cancer without an increased readmission risk, a finding supporting this accelerated discharge target inclusion in lobectomy enhanced recovery after surgery protocols., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Ventilator-induced diaphragm dysfunction (VIDD) is an important phenomenon that has been repeatedly demonstrated in experimental and clinical models of mechanical ventilation. Even a few hours of MV initiates signaling cascades that result in, first, reduced specific force, and later, atrophy of diaphragm muscle fibers. This severe, progressive weakness of the critical ventilatory muscle results in increased duration of MV and thus increased MV-associated complications/deaths. A drug that could prevent VIDD would likely have a major positive impact on intensive care unit outcomes. We identified the JAK/STAT pathway as important in VIDD and then demonstrated that JAK inhibition prevents VIDD in rats. We subsequently developed a clinical model of VIDD demonstrating reduced contractile force of isolated diaphragm fibers harvested after ∼7 vs ∼1 h of MV during a thoracic surgical procedure., Materials and Methods: The NIH-funded clinical trial that has been initiated is a prospective, placebo controlled trial: subjects undergoing esophagectomy are randomized to receive 6 preoperative doses of the FDA-approved JAK inhibitor Tofacitinib (commonly used for rheumatoid arthritis) vs. placebo. The primary outcome variable will be the difference in the reduction that occurs in force generation of diaphragm single muscle fibers (normalized to their cross-sectional area), in the Tofacitinib vs. placebo subjects, over 6 h of MV., Discussion: This trial represents a first-in-human, mechanistic clinical trial of a drug to prevent VIDD. It will provide proof-of-concept in human subjects whether JAK inhibition prevents clinical VIDD, and if successful, will support an ICU-based clinical trial that would determine whether JAK inhibition impacts clinical outcome variables such as duration of MV and mortality., (Published by Elsevier Ltd.)

Epithelioid hemangioendothelioma is a rare malignant vascular sarcoma. Here we present a patient with a very large tumor arising from the superior vena cava, in whom a resection with negative margins was accomplished using venovenous bypass and bovine pericardial patch reconstruction of the superior vena cava., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Diaphragm plication (DP) improves pulmonary function and quality of life for those with diaphragm paralysis or dysfunction. It is unknown whether differing degrees of diaphragm dysfunction as measured by sniff testing affect results after plication., Methods: Patients who underwent minimally invasive DP from 2008 to 2019 were dichotomized based on sniff test results: paradoxical motion (PM) versus no paradoxical motion (NPM); the latter included normal, decreased, and no motion. Preoperative and postoperative pulmonary function testing (PFT) after DP was compared between groups. The impact of the diaphragm height index, a measure of diaphragm elevation, was also assessed., Results: A total of 26 patients underwent preoperative sniff testing, DP, and postoperative PFT. Including all patients, DP resulted in a 17.8% ± 5.5% improvement in forced expiratory volume in 1 second (P < .001), a 14.4% ± 5.3% improvement in forced vital capacity (P < .001), and a 4.7% ± 4.6% improvement in the diffusing capacity of carbon monoxide (P = .539). There were greater improvements in the PM group (n = 16) compared with the NPM group (n = 10) for forced expiratory volume in 1 second (27.2% ± 6.0% versus 3.9% ± 6.2%; P = .017) and forced vital capacity (28.1% ± 5.3% versus -0.5% ± 3.3%; P = .001). There was no difference in the change in the diffusing capacity of carbon monoxide between groups. There were no differences between patients with PM and NPM in the postoperative course or complications. No value for diaphragm height index predicted improvement in PFT after DP., Conclusions: Patients with PM on sniff test have dramatically greater objective improvements in pulmonary function after plication compared with those without PM. Most patients without PM do not demonstrate improvement in standard PFT. Improvements in dyspnea require additional study., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Chest radiography is the most frequent and primary imaging modality in the intensive care unit (ICU), given its portability, rapid image acquisition, and availability of immediate information on the bedside preview. Due to the severity of underlying disease and frequent need of placement of monitoring devices, ICU patients are very likely to develop complications related to underlying disease process and interventions. Portable chest radiography in the ICU is an essential tool to monitor the disease process and the complications from interventions; however, it is subject to overuse especially in stable patients. Restricting the use of chest radiographs in the ICU to only when indicated has not been shown to cause harm. The emerging role of bedside point-of-care lung ultrasound performed by the clinicians is noted in the recent literature. The bedside lung ultrasound appears promising but needs cautious evaluation in the future to determine its role in ICU patients. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021. Published by Elsevier Inc.)

Blunt cardiac injuries range from myocardial concussion (commotio cordis) leading to fatal ventricular arrhythmias to myocardial contusion, cardiac chamber rupture, septal rupture, pericardial rupture, and valvular injuries. Blunt injuries account for one-fourth of the traumatic deaths in the United States. Chest radiography, transthoracic echocardiography, CT chest with and without contrast, and CT angiography are usually appropriate as the initial examination in patients with suspected blunt cardiac injury who are both hemodynamically stable and unstable. Transesophageal echocardiography and CT heart may be appropriate as examination in patients with suspected blunt cardiac injuries. This publication of blunt chest trauma-suspected cardiac injuries summarizes the literature and makes recommendations for imaging based on the available data and expert opinion. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2020 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Introduction: Existing guidelines for surveillance after non-small-cell lung cancer (NSCLC) treatment are inconsistent and have relatively sparse supporting literature. This study characterizes detection rates of metachronous and recurrent disease during surveillance with computed tomography scans after definitive treatment of early stage NSCLC., Materials and Methods: The incidence of metachronous and recurrent disease in patients who previously underwent complete resection via lobectomy for stage IA NSCLC at a single center from 1996 to 2010 were evaluated. A subgroup analysis was used to compare survival of patients whose initial surveillance scan was 6 ± 3 months (early) versus 12 ± 3 months (late) after lobectomy., Results: Of 294 eligible patients, 49 (17%) developed recurrent disease (14 local only, 35 distant), and 45 (15%) developed new NSCLC. Recurrent disease was found at a mean of 22 ± 19 months, and new primaries were found at a mean of 52 ± 31 months after lobectomy (P < .01). Five-year survival after diagnosis of recurrent disease was significantly lower than after diagnosis of second primaries (2.3% vs. 57.5%; P < .001). In the subgroup analysis of 187 patients, both disease detection on the initial scan (2% [2/94] vs. 4% [4/93]; P = .44) and 5-year survival (early, 80.8% vs. late, 86.7%; P = .61) were not significantly different between the early (n = 94) and the late (n = 93) groups., Conclusion: Surveillance after lobectomy for stage IA NSCLC is useful for identifying both new primary as well as recurrent disease, but waiting to start surveillance until 12 ± 3 months after surgery is unlikely to miss clinically important findings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: We have previously demonstrated that p-tyramine (TYR), an endogenous trace amine-associated receptor 1 agonist, passage across neuronal membranes involves a transporter exhibiting the pharmacological profile of Organic Cation Transporter 2 (OCT2). Since TYR is also a constituent of foodstuffs and produced by the intestinal microbiota, here we have investigated whether similar processes are involved in the passage of 100 nM TYR across apical and basolateral membranes of the Caco-2 human intestinal epithelial cell line., Materials and Methods: [ 3 H]TYR transport across apical and basolateral membranes of Caco-2 cell monolayers was measured in the presence of inhibitors of TYR metabolizing enzymes. Cellular, apical, and basolateral compartments were collected at various timepoints, TYR concentrations calculated, and transport properties pharmacologically characterized., Key Findings: Apical transport resulted in equimolar accumulation of TYR within cells. Pentamidine (OCT1/OCT2 inhibitor) decreased apical transport (P = 0.001) while atropine (OCT1 inhibitor) had no effect, suggesting apical transport involved OCT2. In contrast, basolateral transport resulted in 500-1000 nM cellular concentrations (P < 0.0001) indicating the presence of an active transporter. Replacement of Na + on an equimolar basis with choline resulted in loss of TYR transport (P = 0.017). Unexpectedly, this active transport was also atropine-sensitive (P = 0.020). Kinetic analysis of the active transporter revealed V max  = 43.0 nM/s with a K t  = 33.1 nM., Significance: We have demonstrated for the first time that TYR is transported across Caco-2 apical membranes via facilitated diffusion by OCT2, whereas transport across basolateral membranes is by a Na + -dependent, atropine-sensitive, active transporter., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Identifying small lung lesions during minimally invasive thoracic surgery can be challenging. We describe 3-dimensional mixed-reality visualization technology that may facilitate noninvasive nodule localization., Description: A software application and medical image processing pipeline were developed for the Microsoft HoloLens to incorporate patient-specific data and provide a mixed-reality tool to explore and manipulate chest anatomy with a custom-designed user interface featuring gesture and voice recognition., Evaluation: A needs assessment between engineering and clinical disciplines identified the potential utility of mixed-reality technology in facilitating safe and effective resection of small lung nodules. Through an iterative process, we developed a prototype employing a wearable headset that allows the user to (1) view a patient's original preoperative imaging; (2) manipulate a 3-dimensional rendering of that patient's chest anatomy including the bronchial, osseus, and vascular structures; and (3) simulate lung deflation and surgical instrument placement., Conclusions: Mixed-reality visualization during surgical planning may facilitate accurate and rapid identification of small lung lesions during minimally invasive surgeries and reduce the need for additional invasive preoperative localization procedures., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Extended thymectomy has been proven to improve the course of myasthenia gravis. Retrospective studies demonstrate that several techniques for thymectomy achieve overlapping remission rates. We therefore compared perioperative outcomes and costs among 3 approaches to thymectomy: sternotomy, video and/or robot assisted, and transcervical., Methods: To ensure similar study groups, we excluded patients with >4 cm or invasive tumors and those who underwent less than an extended thymectomy or concurrent procedures. Hospital costs were collected and analyzed by blinded finance personnel., Results: The final study group consisted of 25 transcervical, 23 video/robot-assisted, and 14 sternotomy subjects. There was a higher incidence of myasthenia gravis in the transcervical and sternotomy groups (P < 0.001) and of thymoma in the video/robot-assisted and sternotomy groups (P = .002). Mean modified Charlson comorbidity score was higher for sternotomy (2.7 ± 2.1, mean ± SD) than transcervical (1.00 ± 0.58; P < .001) and video/robot-assisted (1.13 ± 0.97; P = .001) procedures. There was no difference in complication rates between approaches (P = 0.828). The cost of transcervical thymectomy was 45% of the cost of sternotomy (P < .001), and was 58% of the cost of video/robot-assisted (P = .018) approaches; these differences remained highly significant on multivariate analysis. Transcervical thymectomy had a shorter mean length of stay (1.2 ± 0.5 days) than median sternotomy (4.4 ± 3.5; P < .001), and video/robot-assisted thymectomy (2.4 ± 0.95; P = .045) and "bed cost" were major contributors to the cost difference between the groups., Conclusions: Transcervical thymectomy, which provides overlapping myasthenia gravis remission rates versus more invasive approaches, is equally safe and far less costly than sternotomy and video/robot-assisted approaches., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The objective of this study was to evaluate the impact of a video-assisted thoracoscopic (VATS) approach on outcomes in patients who underwent lobectomy after induction therapy., Methods: Outcomes of patients with T2-T4, N0, M0 and T1-T4, N1-N2, M0 non-small-cell lung cancer who received induction chemotherapy or chemoradiation followed by lobectomy in the National Cancer Data Base (2010-2014) were assessed using Kaplan-Meier, propensity score-matched, multivariable logistic regression and Cox proportional hazards analyses., Results: In the National Cancer Data Base, 2887 lobectomy patients met inclusion criteria (VATS 676 [23%]; thoracotomy 2211 [77%]). Of the VATS cases, patients who underwent induction chemoradiation were more likely to undergo conversion (adjusted odds ratio 1.70, P = .05). Compared with an open approach, VATS was associated with decreased length of stay (median: 5 days vs 6 days, P < .01) and no significant differences in 30-day mortality (VATS [1.5% (n = 10)] vs open [2.6% (n = 58)]; P = .13) and 90-day mortality (VATS [3.7% (n = 25)] vs open [5.6% (n = 124)]; P = .14). There were no significant differences in 5-year survival between the VATS and open groups in both the entire cohort (VATS [50.3%] vs open [52.3%]; P = .83) and in a propensity score-matched analysis of 876 patients; furthermore, a VATS approach was not associated with worse survival in multivariable analysis (hazard ratio 1.02; 95% confidence interval 0.86-1.20; P = .83)., Conclusions: In this national analysis, a VATS approach for lobectomy in patients who received induction therapy for locally advanced non-small-cell lung cancer was not associated with worse short-term or long-term outcomes when compared with an open approach., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Hemoptysis, the expectoration of blood, ranges in severity from nonmassive to massive. This publication reviews the literature on the imaging and treatment of hemoptysis. Based on the literature, the imaging recommendations for massive hemoptysis are both a chest radiograph and CT with contrast or CTA with contrast. Bronchial artery embolization is also recommended in the majority of cases. In nonmassive hemoptysis, both a chest radiograph and CT with contrast or CTA with contrast is recommended. Bronchial artery embolization is becoming more commonly utilized, typically in the setting of failed medical therapy. Recurrent hemoptysis, defined as hemoptysis that recurs following initially successful cessation of hemoptysis, is best reassessed with a chest radiograph and either CT with contrast or CTA with contrast. Bronchial artery embolization is increasingly becoming the treatment of choice in recurrent hemoptysis, with the exception of infectious causes such as in cystic fibrosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2020 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Ordering the appropriate diagnostic imaging for occupational lung disease requires a firm understanding of the relationship between occupational exposure and expected lower respiratory track manifestation. Where particular inorganic dust exposures typically lead to nodular and interstitial lung disease, other occupational exposures may lead to isolated small airway obstruction. Certain workplace exposures, like asbestos, increase the risk of malignancy, but also produce pulmonary findings that mimic malignancy. This publication aims to delineate the common and special considerations associated with occupational lung disease to assist the ordering physician in selecting the most appropriate imaging study, while still stressing the importance of a multidisciplinary approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2020 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Achieving negative margins for adenoid cystic carcinoma (ACC) of the trachea can be technically difficult. This study evaluated the impact of positive margins on prognosis and tested the hypothesis that radiation improves survival in the setting of incomplete resection., Methods: The impact of margin status and adjuvant therapy on overall survival of patients with tracheal ACC in the National Cancer Database (1998 to 2014) who underwent resection with known margin status and with no documented nodal or distant disease was evaluated using Kaplan-Meier and Cox proportional hazard analysis., Results: Of 132 patients who met study criteria, 79 (59.8%) had positive margins after resection. Adjuvant radiation was given to 95 patients overall (72.0%) and to 62 of the 79 patients with positive margins (78.5%). The survival of patients with positive margins was not significantly different from that of patients with negative margins (5-year survival, 82.2% [95% confidence interval (CI), 71.3-89.3] compared with 82.0% [95% CI, 67.0-90.6], P = .97), even after multivariable adjustment (hazard ratio, 1.73; 95% CI, 0.62-4.84; P = .30). In the subset of patients with positive margins, there was no significant difference in survival between patients who did or did not receive postoperative radiation therapy (5-year survival, 82.0% [95% CI, 68.8-89.9] compared with 82.4% [95% CI, 54.7-93.9]; P = .80), even after multivariable adjustment (hazard ratio, 1.04; 95% CI, 0.21-5.25; P = .96)., Conclusions: The majority of tracheal ACC resections performed in this national cohort had positive margins. Adjuvant radiation was commonly used for positive margins but was not associated with an overall survival benefit., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Most clinicians will encounter patients 90 years or older with non-small cell lung cancer (NSCLC), but evidence that informs treatment decisions for this extremely elderly population is lacking. This study evaluated outcomes associated with treatment strategies for this nonagenarian population., Methods: Treatment and overall survival for patients 90 years and older with NSCLC in the National Cancer Data Base (2004-2014) were evaluated using logistic regression, the Kaplan-Meier method, and multivariable Cox proportional hazard models., Results: The majority (n = 4152, 57.6%) of the 7205 patients 90 years or older with stage I-IV NSCLC did not receive any therapy. For the entire cohort, receiving treatment was associated with significantly better survival when compared with no therapy (5-year survival, 9.3% [95% confidence interval [CI], 8.0%-10.7%] vs 1.7% [95% CI, 1.2%-2.2%]; multivariable adjusted hazard ratio, 0.53; P < .001). Stage I patients had the most pronounced survival benefit with treatment (median survival, 27.4 months vs 10.0 months with no treatment; P < .001). Among this subset of patients with stage I disease (n = 1430), only 12.7% (n = 182) had surgery and 33% (n = 471) had no therapy. In these stage I patients surgery was associated with significantly better 5-year survival (33.7% [95% CI, 25.4%-42.1%]) than nonoperative therapy (17.1% [95% CI, 13.7%-20.8%]) and no therapy (6.2% [95% CI, 3.8%-9.4%])., Conclusions: Therapy for nonagenarians with NSCLC is associated with a significant survival benefit but is not used in most patients. Treatment should not be withheld for these "oldest old" patients based on their age alone but should be considered based on stage and patient preferences in a multidisciplinary setting., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The immunocompromised patient with an acute respiratory illness (ARI) may present with fever, chills, weight loss, cough, shortness of breath, or chest pain. The number of immunocompromised patients continues to rise with medical advances including solid organ and stem cell transplantation, chemotherapy, and immunomodulatory therapy, along with the continued presence of human immunodeficiency virus and acquired immunodeficiency syndrome. Given the myriad of pathogens that can infect immunocompromised individuals, identifying the specific organism or organisms causing the lung disease can be elusive. Moreover, immunocompromised patients often receive prophylactic or empiric antimicrobial therapy, further complicating diagnostic evaluation. Noninfectious causes for ARI should also be considered, including pulmonary edema, drug-induced lung disease, atelectasis, malignancy, radiation-induced lung disease, pulmonary hemorrhage, diffuse alveolar damage, organizing pneumonia, lung transplant rejection, and pulmonary thromboembolic disease. As many immunocompromised patients with ARI progress along a rapid and potentially fatal course, timely selection of appropriate imaging is of great importance in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking, or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Hydrogen peroxide (H 2 O 2 ) is used as anti-parasitic veterinary medicine in salmon farms worldwide. In the period from 2009 to 2018 a total of 135 million kg of H 2 O 2 was used in Norway, the world's largest producer of Atlantic salmon. Since the treatment water is discharged to the sea, concerns have been raised about effects of H 2 O 2 on the coastal ecosystem. In the present study, Northern shrimp (Pandalus borealis) have been exposed to short pulses of H 2 O 2 in the PARAMOVE ® formulation, followed by a recovery period in clean seawater. The exposure concentrations represented 100, 1000 and 10 000 times dilutions of the prescribed treatment concentration for salmon; 15 mg/L, 1.5 mg/L and 0.15 mg/L H 2 O 2 . Significantly increased mortality was observed after 2 h exposure to 15 mg/L H 2 O 2 (50%) and after 2 h exposure to 1.5 mg/L H 2 O 2 on 3 consecutive days (33%), but no mortality was observed after 2 h exposure to 0.15 mg/L. The mortality occurred 2-4 days after the first pulse of exposure. The patterns of acute effects (immobility and death) could be captured with a toxicokinetic-toxicodynamic model (GUTS), which allows extrapolations to LC50s for constant exposure, or thresholds for effects given untested exposure profiles. Effects of H 2 O 2 were also detected in shrimp that survived until the end of the recovery period. The feeding rate was 66% lower than in the control after 12 days of recovery for the three-pulse 1.5 mg/L exposure. Furthermore, dose dependent tissue damage was detected in the gills and evidence of lipid peroxidation in the hepatopancreas in shrimp exposed for 1 h to 1.5 mg/L and 15 mg/L and kept in recovery for 8 days. Fluorescence intensity in the hepatopancreas of treated shrimp increased 47% and 157% at 1.5 mg/L and 15 mg/L, respectively, compared to the control. Local hydrodynamic conditions will determine how fast the concentration of H 2 O 2 will be diluted and how far it will be transported horizontally and vertically. Results from dispersion modelling (literature data) together with the current experiments indicate that treatment water with toxic concentrations of H 2 O 2 (1.5 mg/L) could reach P. borealis living more than 1 km from a treated salmon farm., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Current guidelines do not routinely recommend adjuvant therapy for resected stage I large cell lung neuroendocrine cancer (LCNEC). However, data regarding the role of adjuvant therapy in early LCNEC are limited. This National Cancer Database (NCDB) analysis was performed to improve the evidence guiding adjuvant therapy for early LCNEC., Methods: Overall survival (OS) of patients with pathologic T1-2a N0 M0 LCNEC who underwent resection in the NCDB from 2003 to 2015 was evaluated with Kaplan-Meier and multivariable Cox proportional hazards analyses. Patients who died within 30 days of surgery and with more than R0 resection were excluded., Results: Of 2642 patients meeting study criteria, 481 (18%) received adjuvant therapy. Adjuvant chemotherapy in stage IB patients was associated with a significant increase in OS (hazard ratio, 0.67; 95% confidence interval, 0.50 to 0.90). However, there was no significant difference in survival between adjuvant chemotherapy and no adjuvant therapy for stage IA LCNEC (hazard ratio, 0.92; 95% confidence interval, 0.75 to 1.11). Adjuvant radiotherapy, whether alone or combined with chemotherapy, was not associated with a change in OS. In subgroup analysis, patients receiving adjuvant chemotherapy after lobar resection for stage IB LCNEC had a significant survival benefit compared with patients not receiving adjuvant therapy., Conclusions: In early-stage LCNEC, adjuvant chemotherapy appears to confer an additional overall survival advantage only in patients with completely resected stage IB LCNEC and not for patients with completely resected stage IA LCNEC., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Lung cancer is the leading cause of cancer-related deaths in both men and women. The major risk factor for lung cancer is personal tobacco smoking, particularly for small-cell lung cancer (SCLC) and squamous cell lung cancers, but other significant risk factors include exposure to secondhand smoke, environmental radon, occupational exposures, and air pollution. Education and socioeconomic status affect both incidence and outcomes. Non-small-cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, comprises about 85% of lung cancers. SCLC accounts for approximately 13% to 15% of cases. Prognosis is directly related to stage at presentation. NSCLC is staged using the eighth edition of the tumor-node-metastasis (TNM) criteria of the American Joint Committee on Cancer. For SCLC the eighth edition of TNM staging is recommended to be used in conjunction with the modified Veterans Administration Lung Study Group classification system distinguishing limited stage from extensive stage SCLC. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: A right-sided pneumonectomy after induction therapy for non-small cell lung cancer (NSCLC) has been shown to be associated with significant perioperative risk. We examined the effect of laterality on long-term survival after induction therapy and pneumonectomy using the National Cancer Data Base., Methods: Perioperative and long-term outcomes of patients who underwent pneumonectomy after induction chemotherapy, with or without radiotherapy, from 2004 to 2014 in the National Cancer Data Base were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis., Results: During the study period, 1,465 patients (right, 693 [47.3%]; left, 772 [52.7%]) met inclusion criteria. Right-sided pneumonectomy was associated with significantly higher 30-day (8.2% [57 of 693] vs 4.2% [32 of 772], p < 0.01) and 90-day mortality (13.6% [94 of 693] vs 7.9% [61 of 772], p < 0.01), and right-sided pneumonectomy was a predictor of higher 90-day mortality (odds ratio, 2.23; p < 0.01). However, overall 5-year survival between right and left pneumonectomy was not significantly different in unadjusted (37.6% [95% confidence interval {CI}, 0.34 to 0.42] vs 35% [95% CI, 0.32 to 0.39], log-rank p = 0.94) or multivariable analysis (hazard ratio, 1.07; 95% CI, 0.92 to 1.25; p = 0.40). A propensity score-matched analysis of 810 patients found no significant differences in 5-year survival between the right-sided versus left-sided groups (34.7% [95% CI, 0.30 to 0.40] vs 34.1%, [95% CI, 0.29 to 0.39], log-rank p = 0.86)., Conclusions: In this national analysis, right-sided pneumonectomy after induction therapy was associated with a significantly higher perioperative but not worse long-term mortality compared to a left-sided procedure., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The present study examined clinical stage I non-small-cell lung cancer (NSCLC) treatment in the population-based California Cancer Registry., Patients and Methods: The characteristics associated with first clinical stage I NSCLC treatment (surgery, radiation, no local therapy) from 2003 to 2014 were identified using logistic regression. Survival was evaluated using Kaplan-Meier and Cox proportional hazard analyses., Results: Surgery was used in most patients who met the inclusion criteria (14,545 of 19,893; 73.1%), although relatively similar numbers had undergone radiation (n = 2848; 14.3%) or not received therapy (n = 2500; 12.6%). Surgery use ranged from 68.5% to 77.2% patients annually. The percentage of patients with no therapy decreased from 18.1% (315 of 1737) in 2003 to 10.3% (176 of 1703) in 2014, and radiation use increased from 10.7% (185 of 1737) in 2003 to 21.2% (361 of 1703) in 2014. Patients who did not receive therapy were more likely to be older, not white, male, and unmarried, to have no insurance or public insurance other than Medicare, to live in a lower socioeconomic status neighborhood, to have been seen at a non-National Cancer Institute cancer center hospital or hospital serving lower socioeconomic status patients, and to have larger tumors. The 5-year all-cause survival after no therapy (12.7%) was significantly worse than that after surgery (64.9%) or radiation (21.5%; P < .0001)., Conclusion: In the present population-based analysis, surgery was the most common treatment for clinical stage I NSCLC but was not used for almost 27% of patients. Radiation use increased and the proportion of patients who did not receive any therapy decreased over time., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to evaluate the safety and feasibility of using neoadjuvant chemotherapy plus ipilimumab followed by surgery as a treatment strategy for stage II-IIIA non-small cell lung cancer., Methods: From 2013 to 2017, postoperative data from patients who underwent surgery after neoadjuvant chemotherapy plus ipilimumab in the TOP1201 trial, an open label phase II trial (NCT01820754), were prospectively collected. The surgical outcomes from TOP1201 were compared with outcomes in a historical cohort of patients receiving standard preoperative chemotherapy followed by surgery identified from our institution's prospectively collected thoracic surgery database., Results: In the TOP1201 trial, 13 patients were treated with preoperative chemotherapy and ipilimumab followed by surgery. In the historical cohort, 42 patients received preoperative chemotherapy by a platinum doublet regimen preoperative chemotherapy by a platinum doublet regimen without ipilimumab followed by lobectomy or pneumonectomy. The 30-day mortality in both groups was 0%. The most frequently occurring perioperative complications in the TOP1201 group were prolonged air leak (n = 2, 15%) and urinary tract infection (n = 2, 15%). The most common perioperative complication in the preoperative chemotherapy alone group was atrial fibrillation (n = 6, 14%). One patient (8%) had atrial fibrillation in the TOP1201 group. There was no apparent increased occurrence of adverse surgical outcomes for patients in the TOP1201 group compared with patients receiving standard of care neoadjuvant chemotherapy alone before surgery for stage II-IIIA non-small cell lung cancer., Conclusions: This report is the first to demonstrate the safety and feasibility of surgical resection after treatment with ipilimumab and chemotherapy in stage II-IIIA non-small-cell lung cancer., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The obesity epidemic in the United States has increased greatly over the past several decades, and thoracic surgeons are likely to see obese patients routinely in their practices. Obesity has direct deleterious health effects such as metabolic disorder and cardiovascular disease, and is associated with many cancers. Obese patients who need thoracic surgery pose practical challenges to many of the routine elements in perioperative management. Preoperative assessment of obesity-related comorbid conditions and risk stratification for surgery, thorough intraoperative planning for anesthesia and surgery, and postoperative strategies to optimize pulmonary hygiene and mobility minimize the risk of adverse outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: While lepidic-predominant lung adenocarcinomas are known to have better outcomes than similarly sized solid tumors, the impact of smaller noninvasive foci within predominantly solid tumors is less clearly characterized. We tested the hypothesis that lung adenocarcinomas with even a small ground-glass opacity (GGO) component have a better prognosis than otherwise similar pure solid (PS) adenocarcinomas., Patients and Methods: The maximum total and solid-component diameters were determined by preoperative computed tomography in patients who underwent lobar or sublobar resection of clinical N0 adenocarcinomas without induction therapy between May 2003 and August 2013. Survival between patients with PS tumors (0% GGO) or tumors with a minor ground-glass (MGG) component (1%-25% GGO) was compared by Kaplan-Meier and Cox analyses., Results: A total of 123 patients met the inclusion criteria, comprising 54 PS (44%) and 69 MGG (56%) whose mean ground-glass component was 18 ± 7%. The solid component tumor diameter was not significantly different between the groups (2.3 ± 1.2 cm vs. 2.5 ± 1.3 cm, P = .2). Upstaging to pN1-2 was more common for the PS group (13% [7/54] vs. 3% [2/69], P = .04), but the distribution of pathologic stage was not significantly different between the groups (PS 76% stage I [41/54] vs. MGG 80% stage I [55/69], P = .1). Having a MGG component was associated with markedly better survival in both univariate analysis (MGG 5-year overall survival 86.7% vs. PS 64.5%, P = .001) and multivariable survival analysis (hazard ratio, 0.30, P = .01)., Conclusion: Patients with resected cN0 lung adenocarcinoma who have even a small GGO component have markedly better survival than patients with PS tumors, which may have implications for both treatment and surveillance strategies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Because the relationship between the timing of surgery following diagnosis of lung cancer and survival has not been precisely described, guidelines on what constitutes a clinically meaningful delay of resection of early-stage lung cancer do not exist. This study tested the hypothesis that increasing the time between diagnosis and lobectomy for stage IA squamous cell carcinoma (SCC) would be associated with worse survival., Methods: The association between timing of lobectomy and survival for patients with clinical stage IA SCC in the National Cancer Data Base (2006-2011) was assessed using multivariable Cox proportional hazards analysis and restricted cubic spline (RCS) functions., Results: The 5-year overall survival of 4,984 patients who met study inclusion criteria was 58.3% (95% CI, 56.3-60.2). Surgery was performed within 30 days of diagnosis in 1,811 (36%) patients, whereas the median time to surgery was 38 days (interquartile range, 23, 58). In multivariable analysis, patients who had surgery 38 days or more after diagnosis had significantly worse 5-year survival than patients who had surgery earlier (hazard ratio, 1.13 [95% CI, 1.02-1.25]; P = .022). Multivariable RCS analysis demonstrated the hazard ratio associated with time to surgery increased steadily the longer resection was delayed; the threshold time associated with statistically significant worse survival was ∼90 days or greater., Conclusions: Longer intervals between diagnosis of early-stage lung SCC and surgery are associated with worse survival. Although factors other than the timing of treatment may contribute to this finding, these results suggest that efforts to minimize delays beyond those needed to perform a complete preoperative evaluation may improve survival., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Although the use of adjuvant chemotherapy in patients with pathologically node-positive (pN+) atypical carcinoid tumor of the lung is an accepted practice, controversy exists about its use in pathologically node-negative (pN0) patients. Our aim was to determine whether a survival advantage exists in patients receiving chemotherapy postoperatively for pN0 or pN+ atypical carcinoid tumors of the lung., Methods: Adult patients treated with lobectomy or pneumonectomy for pulmonary atypical carcinoid tumor were identified using the National Cancer Data Base, 2006 to 2011. Propensity scoring (4:1 nearest neighbor algorithm) and survival analysis were used to examine the association between adjuvant chemotherapy and pN+ versus pN0 atypical carcinoid tumors., Results: Of the total 581 patients identified with a diagnosis of atypical carcinoid of the lung, 363 (62.5%) were found to be node negative at the time of operation and 218 (37.5%) had node-positive disease. Adjuvant chemotherapy was used in 15 patients (4.1%) with pN0 disease and 89 patients (40.8%) with pN+ disease. Unadjusted survival, at 12 and 60 months, was similar between pN+ patients who were treated with adjuvant chemotherapy versus patients who received operation alone (adjuvant chemotherapy: 98.9% at 12 months and 47.9% at 60 months versus operation alone: 98.4% and 12 months and 67.1% at 60 months, p = 0.46) and for propensity-matched pN0 (adjuvant chemotherapy: 86.7% at 12 months and 73.3% at 60 months versus operation alone: 87.9% at 12 months and 72.3% at 60 months, p = 0.54)., Conclusions: In a national-level analysis, the use of adjuvant chemotherapy postoperatively in patients with pN+ and pN0 disease conferred no survival advantage; further study is needed to determine proper chemotherapy use for these patients., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Black patients with esophageal cancer have worse survival than white patients. This study examines this racial disparity in conjunction with socioeconomic status (SES) and explores whether race-based outcome differences exist using a national database., Methods: The associations between race and SES with overall survival of patients treated with esophagectomy for stages I to III esophageal cancer between 2003 and 2011 in the National Cancer Data Base were investigated using the Kaplan-Meier method and proportional hazards analyses. Median income by zip code and proportion of the zip code residents without a high school diploma were grouped into income and education quartiles, respectively and used as surrogates for SES. The association between race and overall survival stratified by SES is explored., Results: Of 11,599 esophagectomy patients who met study criteria, 3,503 (30.2%) were in the highest income quartile, 2,847 (24.5%) were in the highest education quartile, and 610 patients (5%) were black. Before adjustment for SES, black patients had worse overall survival than white patients (median survival 23.0 versus 34.7 months, log rank p < 0.001), and overall, survival times improved with increasing income and education (p < 0.001 for both). After adjustment for putative prognostic factors, SES was associated with overall survival, whereas race was not., Conclusions: Prior studies have suggested that survival of esophageal cancer patients after esophagectomy is associated with race. Our study suggests that race is not significantly related to overall survival when adjusted for other prognostic variables. Socioeconomic status, however, remains significantly related to overall survival in our model., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)