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In this contribution, we achieve the primary goal of the active galactic nucleus (AGN) STORM campaign by recovering velocity-delay maps for the prominent broad emission lines (Lyα, C iv, He ii, and Hβ) in the spectrum of NGC 5548. These are the most detailed velocity-delay maps ever obtained for an AGN, providing unprecedented information on the geometry, ionization structure, and kinematics of the broad-line region. Virial envelopes enclosing the emission-line responses show that the reverberating gas is bound to the black hole. A stratified ionization structure is evident. The He ii response inside 5-10 lt-day has a broad single-peaked velocity profile. The Lyα, C iv, and Hβ responses extend from inside 2 to outside 20 lt-day, with double peaks at ±2500 km s-1 in the 10-20 lt-day delay range. An incomplete ellipse in the velocity-delay plane is evident in Hβ. We interpret the maps in terms of a Keplerian disk with a well-defined outer rim at R = 20 lt-day. The far-side response is weaker than that from the near side. The line-center delay days gives the inclination i ≈ 45°. The inferred black hole mass is M BH ≈ 7 × 107 M o˙. In addition to reverberations, the fit residuals confirm that emission-line fluxes are depressed during the "BLR Holiday"identified in previous work. Moreover, a helical "Barber-Pole"pattern, with stripes moving from red to blue across the C iv and Lyα line profiles, suggests azimuthal structure rotating with a 2 yr period that may represent precession or orbital motion of inner-disk structures casting shadows on the emission-line region farther out.

We present geometric and dynamical modeling of the broad line region (BLR) for the multi-wavelength reverberation mapping campaign focused on NGC 5548 in 2014. The data set includes photometric and spectroscopic monitoring in the optical and ultraviolet, covering the Hβ, C iv, and Ly broad emission lines. We find an extended disk-like Hβ BLR with a mixture of near-circular and outflowing gas trajectories, while the C iv and Ly BLRs are much less extended and resemble shell-like structures. There is clear radial structure in the BLR, with C iv and Ly emission arising at smaller radii than the Hβ emission. Using the three lines, we make three independent black hole mass measurements, all of which are consistent. Combining these results gives a joint inference of . We examine the effect of using the V band instead of the UV continuum light curve on the results and find a size difference that is consistent with the measured UV-optical time lag, but the other structural and kinematic parameters remain unchanged, suggesting that the V band is a suitable proxy for the ionizing continuum when exploring the BLR structure and kinematics. Finally, we compare the Hβ results to similar models of data obtained in 2008 when the active galactic nucleus was at a lower luminosity state. We find that the size of the emitting region increased during this time period, but the geometry and black hole mass remained unchanged, which confirms that the BLR kinematics suitably gauge the gravitational field of the central black hole.

We model the ultraviolet spectra of the Seyfert 1 galaxy NGC 5548 obtained with the Hubble Space Telescope during the 6 month reverberation mapping campaign in 2014. Our model of the emission from NGC 5548 corrects for overlying absorption and deblends the individual emission lines. Using the modeled spectra, we measure the response to continuum variations for the deblended and absorption-corrected individual broad emission lines, the velocity-dependent profiles of Ly and C iv, and the narrow and broad intrinsic absorption features. We find that the time lags for the corrected emission lines are comparable to those for the original data. The velocity-binned lag profiles of Ly and C iv have a double-peaked structure indicative of a truncated Keplerian disk. The narrow absorption lines show a delayed response to continuum variations corresponding to recombination in gas with a density of ∼105 cm-3. The high-ionization narrow absorption lines decorrelate from continuum variations during the same period as the broad emission lines. Analyzing the response of these absorption lines during this period shows that the ionizing flux is diminished in strength relative to the far-ultraviolet continuum. The broad absorption lines associated with the X-ray obscurer decrease in strength during this same time interval. The appearance of X-ray obscuration in ∼2012 corresponds with an increase in the luminosity of NGC 5548 following an extended low state. We suggest that the obscurer is a disk wind triggered by the brightening of NGC 5548 following the decrease in size of the broad-line region during the preceding low-luminosity state.

During the Space Telescope and Optical Reverberation Mapping Project observations of NGC 5548, the continuum and emission-line variability became decorrelated during the second half of the six-month-long observing campaign. Here we present Swift and Chandra X-ray spectra of NGC 5548 obtained as part of the campaign. The Swift spectra show that excess flux (relative to a power-law continuum) in the soft X-ray band appears before the start of the anomalous emission-line behavior, peaks during the period of the anomaly, and then declines. This is a model-independent result suggesting that the soft excess is related to the anomaly. We divide the Swift data into on- and off-anomaly spectra to characterize the soft excess via spectral fitting. The cause of the spectral differences is likely due to a change in the intrinsic spectrum rather than to variable obscuration or partial covering. The Chandra spectra have lower signal-to-noise ratios, but are consistent with the Swift data. Our preferred model of the soft excess is emission from an optically thick, warm Comptonizing corona, the effective optical depth of which increases during the anomaly. This model simultaneously explains all three observations: the UV emission-line flux decrease, the soft-excess increase, and the emission-line anomaly.

We present the results of an optical spectroscopic monitoring program targeting NGC 5548 as part of a larger multiwavelength reverberation mapping campaign. The campaign spanned 6 months and achieved an almost daily cadence with observations from five ground-based telescopes. The Hβ and He ii λ4686 broad emission-line light curves lag that of the 5100 +-optical continuum by 4.17+0.36-0.36 and 0.79+0.35-0.34 days, respectively. The Hβ lag relative to the 1158 ultraviolet continuum light curve measured by the Hubble Space Telescope is ∼50% longer than that measured against the optical continuum, and the lag difference is consistent with the observed lag between the optical and ultraviolet continua. This suggests that the characteristic radius of the broad-line region is ∼50% larger than the value inferred from optical data alone. We also measured velocity-resolved emission-line lags for Hβ and found a complex velocity-lag structure with shorter lags in the line wings, indicative of a broad-line region dominated by Keplerian motion. The responses of both the Hβ and He ii emission lines to the driving continuum changed significantly halfway through the campaign, a phenomenon also observed for C iv, Lyα, He ii(+O iii]), and Si iv(+O iv]) during the same monitoring period. Finally, given the optical luminosity of NGC 5548 during our campaign, the measured Hβ lag is a factor of five shorter than the expected value implied by the R BLR-L AGN relation based on the past behavior of NGC 5548.

We analyze how passive galaxies at z ∼ 1.5 populate the mass-size plane as a function of their stellar age, to understand if the observed size growth with time can be explained with the appearance of larger quenched galaxies at lower redshift. We use a sample of 32 passive galaxies extracted from the Wide Field Camera 3 Infrared Spectroscopic Parallel (WISP) survey with spectroscopic redshift 1.3 ≲ z ≲ 2.05, specific star formation rates lower than 0.01 Gyr-1, and stellar masses above 4.5 × 1010 M Ȯ. All galaxies have spectrally determined stellar ages from fitting of their rest-frame optical spectra and photometry with stellar population models. When dividing our sample into young (age ≤2.1 Gyr) and old (age >2.1 Gyr) galaxies we do not find a significant trend in the distributions of the difference between the observed radius and that predicted by the mass-size relation. This result indicates that the relation between the galaxy age and its distance from the mass-size relation, if it exists, is rather shallow, with a slope α -0.6. At face value, this finding suggests that multiple dry and/or wet minor mergers, rather than the appearance of newly quenched galaxies, are mainly responsible for the observed time evolution of the mass-size relation in passive galaxies.

The majority of massive disk galaxies in the local Universe show a stellar barred structure in their central regions, including our Milky Way 1,2 . Bars are supposed to develop in dynamically cold stellar disks at low redshift, as the strong gas turbulence typical of disk galaxies at high redshift suppresses or delays bar formation 3,4 . Moreover, simulations predict bars to be almost absent beyond z = 1.5 in the progenitors of Milky Way-like galaxies 5,6 . Here we report observations of ceers-2112, a barred spiral galaxy at redshift z phot  ≈ 3, which was already mature when the Universe was only 2 Gyr old. The stellar mass (M ★  = 3.9 × 10 9  M ⊙ ) and barred morphology mean that ceers-2112 can be considered a progenitor of the Milky Way 7-9 , in terms of both structure and mass-assembly history in the first 2 Gyr of the Universe, and was the closest in mass in the first 4 Gyr. We infer that baryons in galaxies could have already dominated over dark matter at z ≈ 3, that high-redshift bars could form in approximately 400 Myr and that dynamically cold stellar disks could have been in place by redshift z = 4-5 (more than 12 Gyrs ago) 10,11 ., (© 2023. The Author(s).)

Background: Whether robotic segmentectomies are advantageous is unclear. We describe our experience with the robot, comparing patient populations and outcomes with video-assisted thoracoscopic surgery (VATS) and open resection., Methods: Patients who underwent anatomic segmentectomy from 2004 to 2019 were reviewed. Resection methods were categorized as robotic, VATS, or open. Segmentectomies were categorized as simple or complex. Baseline characteristics and perioperative outcomes were analyzed from 2015 to 2019 due to implementation of the Enhanced Recovery After Surgery pathway for all thoracic surgery patients and to thus minimize confounders resulting from the Enhanced Recovery After Surgery protocol., Results: Since 2004, an increase has occurred in segmentectomies, including robotic and complex segmentectomies. Of the 222 segmentectomies performed from 2015 to 2019, 77 (35%) were robotic, 40 VATS (18%), and 105 open (47%). More complex segmentectomies were performed in the robotic group compared with VATS and open (45% vs 15% vs 22%; P < .001). Operative time for robotic resections were longer compared with VATS and open (205 vs 147 vs 147 minutes; P < .001) but had lower blood loss (50 vs 75 vs 100 mL; P < .001) and shorter chest tube days (2 vs 2 vs 3 days; P = .004) and lengths of stay (3 vs 3 vs 4 days; P < .001). Perioperative mortality was low in all groups. No robotic segmentectomy was converted to open compared with 7.5% for VATS (P = .038). Prolonged air leak was lower for robotic compared with open (4% vs 13%; P = .038)., Conclusions: Robotic segmentectomy has increased in our institution, with a concurrent rise in atypical segmentectomies. Despite performing more complex procedures, there were no conversions and low perioperative morbidity and mortality. Our results suggest that the robotic platform can facilitate performance of complex anatomic segmentectomies., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Psychiatric comorbidities (PCs) have been associated with poor surgical outcomes in several malignancies. However, the impact of PCs on surgical outcomes for non-small cell lung cancer (NSCLC) remains largely unknown., Methods: NSCLC patients who underwent pulmonary resection at a single institution between 2006 and 2017 were included. Presence of preoperative PCs was identified by documented diagnostic codes. Demographic, histopathologic, perioperative, and survival data were analyzed. Categorical variables were compared using the χ 2 or Fisher exact test. Overall and disease-free survival was analyzed using Kaplan-Meier method. Univariable and multivariable logistic regression analyses were performed for 30-day readmission., Results: Among 2907 patients, PCs were present preoperatively in 180 (6%), including anxiety, 130 (72%); depression, 52 (29%); adjustment disorder, 28 (16%); alcohol abuse, 16 (9%); sleep disorder, 8 (4%); and schizophrenia, 3 (2%). Patients with PCs were younger, with fewer cardiovascular complications. There were no differences in length of stay. However, PCs led to increased 30-day readmission (12% vs 6%, P = .004). Reasons for readmission did not differ between groups (P = .679). Multivariable analysis showed PCs independently predicted 30-day readmission (odds ratio, 2.00; P = .005). Importantly, there were no differences in 30- or 90-day mortality (P = .495 and P = .748, respectively), overall survival (P = .439), or disease-free survival (P = .924)., Conclusions: NSCLC patients with and without PCs experienced similar perioperative and long-term outcomes, suggesting that individuals should not be denied surgical care on the basis of such comorbidities. However, further research should seek to identify reasons for increased risk of readmission for patients with PCs and validate these findings in other settings., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Whether extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D) is the optimal resection for malignant pleural mesothelioma remains controversial. We therefore compared perioperative outcomes and long-term survival of patients who underwent EPP versus P/D., Methods: Patients with the diagnosis of malignant pleural mesothelioma who underwent either EPP or P/D from 2000 to 2019 were identified from our departmental database. Propensity score matching was performed to minimize potential confounders for EPP or P/D. Survival analysis was performed by the Kaplan-Meier method and Cox multivariable analysis., Results: Of 282 patients, 187 (66%) underwent EPP and 95 (34%) P/D. Even with propensity score matching, perioperative mortality was significantly higher for EPP than for P/D (11% vs 0%; P = .031); when adjusted for perioperative mortality, median overall survival between EPP and P/D was 15 versus 22 months, respectively (P = .276). Cox multivariable analysis for the matched cohort identified epithelioid histology (hazard ratio [HR], 0.56; P = .029), macroscopic complete resection (HR, 0.41; P = .004), adjuvant radiation therapy (HR, 0.57; P = .019), and more recent operative years (HR, 0.93; P = .011)-but not P/D-to be associated with better survival. Asbestos exposure (HR, 2.35; P = .003) and pathologic nodal disease (HR, 1.61; P = .048) were associated with worse survival., Conclusions: In a multimodality treatment setting, P/D and EPP had comparable long-term oncologic outcomes, although P/D had much lower perioperative mortality. The goal of surgical cytoreduction should be macroscopic complete resection achieved by the safest operation a patient can tolerate., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Little is known regarding the impact of operating room (OR) personnel generation on their perceptions to various surgeon behaviors. We aimed to characterize these relationships by evaluating their responses to 5 realistic intraoperative scenarios., Methods: Operating room personnel were asked to assess surgeon OR behavior across a standardized set of 5 scenarios via an online survey. For each scenario, respondents were asked to identify the behavior as either acceptable, unacceptable but would ignore, unacceptable and would confront the surgeon, or unacceptable and would report to management. Chi-squared analyses were used to compare responses to surgeon behavior with respondent generation., Results: There were 3101 respondents, of which 41% of respondents were baby boomers (n = 1280), 31% were generation (Gen) X (n = 955), and 28% were Gen Y (n = 866). Overall, when compared to Gen X or Gen Y, baby boomers were significantly more likely to find surgeon behaviors of impatience ( P < .001), being late for a case ( P < .001), swearing in the OR ( P < .001), and shouting with a bleeding patient ( P = .001) to be inappropriate and would talk to the surgeon. Alternatively, Gen Y respondents were more likely to find fault with surgeon behaviors that deviate from rules and regulations, such as forgetting a time-out ( P = .001), when compared to baby boomers and Gen X respondents., Discussion: Results of our study demonstrate that OR personnel generation affects their perceptions and response to surgeon behavior. Understanding these tendencies can guide efforts to improve OR interactions among team members.

Duty-hour restrictions have implications on trainee operative exposure necessary to meet minimum case-volume requirements. We utilized a previously validated simulation model to evaluate the effect of program volume, trainee numbers and complement, and rotation schedule on the probability of achieving adequate esophagectomy case numbers for cardiothoracic surgery trainees. A ProModel simulator centered on probabilistic distributions of operative cases was utilized. Historical data from five 2-year cardiothoracic surgery training programs were obtained from 2016-2018 and used as inputs to the simulator that generated 10,000 "trainee 2-year periods" per program. Programs varied in annual average esophagectomy volume (12-91 per year), with 2-4 trainees graduating over a 2-year training period. If esophagectomy cases were distributed solely based on scheduling and institutional volume, only 60% of evaluated programs could adequately expose all trainees in esophagectomy to meet case requirements. The 3 programs with adequate esophagectomy volumes had averaged 3.3 times (range 3.0-3.6) the minimum number of board-required cases for their programs' trainees. The ability of programs to provide trainees with adequate esophagectomy volume is challenging based on institutional volume and scheduling. Through simulation, we demonstrate that programs need >2 times the expected minimum number of esophagectomies to ensure that >90% of trainees meet case-volume requirements. Programs may consider strategies such as allowing trainees to select cases based on personal need, train fewer fellows, or enable trainees to seek subspecialty exposure externally to achieve minimum esophagectomy case-load requirements., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes., Methods: Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC., Results: SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival., Conclusions: We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated., Methods: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response., Results: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001)., Conclusion: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives: Adoptive T-cell therapies (ACTs) using expansion of tumor-infiltrating lymphocyte (TIL) populations are of great interest for advanced malignancies, with promising response rates in trial settings. However, postoperative outcomes following pulmonary TIL harvest have not been widely documented, and surgeons may be hesitant to operate in the setting of widespread disease., Methods: Patients who underwent pulmonary TIL harvest were identified, and postoperative outcomes were studied, including pulmonary, cardiovascular, infectious, and wound complications., Results: 83 patients met inclusion criteria. Pulmonary TIL harvest was undertaken primarily via a thoracoscopy with a median operative blood loss and duration of 30 ml and 65 min, respectively. The median length of stay was 2 days. Postoperative events were rare, occurring in only five (6%) patients, including two discharged with a chest tube, one discharged with oxygen, one episode of urinary retention, and one blood transfusion. No reoperations occurred. The median time from TIL harvest to ACT infusion was 37 days., Conclusions: Pulmonary TIL harvest is safe and feasible, without major postoperative events in our cohort. All patients were able to receive intended ACT infusion without delays. Therefore, thoracic surgeons should actively participate in ongoing ACT trials and aggressively seek to enroll patients on these protocols., (© 2021 Wiley Periodicals LLC.)

Background: Most patients undergoing esophagectomy will experience intermittent reflux of gastric and biliary content into the remnant esophagus postoperatively. The incidence of new or recurrent intestinal metaplasia following chemoradiation and surgery has not been well-described. Furthermore, post-resection guidelines do not exist regarding surveillance for metaplasia in the esophageal remnant., Methods: Patients undergoing Ivor Lewis esophagectomy after concurrent chemoradiation for a diagnosis of esophageal adenocarcinoma from 2006 to 2018 were identified. Pathology records were reviewed for the presence of intestinal metaplasia on pretreatment biopsies, surgical specimen, or post-resection biopsies., Results: In total, 619 patients met inclusion criteria, including 267 (43%) who had intestinal metaplasia noted either prior to or at the time of esophagectomy. The median duration of metaplastic disease prior to resection was 4.4 months. During a median follow-up time of 28 months (interquartile range, 12-60), intestinal metaplasia was noted in the remnant esophagus in 12 (2%) patients, 7 of whom had a prior history of metaplasia. Local recurrence of adenocarcinoma was also uncommon, and occurred in 37/577 (6%) of patients with complete resections, with similar event rates among those with and without a prior history of metaplasia (14/249 [6%] vs. 23/328 [7%], p = 0.614)., Conclusions: Our findings suggest that despite several factors predisposing to mucosal damage following esophagectomy, occurrence of new intestinal metaplasia after trimodality therapy in our patient population appears to be rare, even among patient with a previous history of this pathologic finding, which may have significant implications for surveillance and cost-savings after resection., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: We have previously demonstrated that Enhanced Recovery After Surgery protocols are associated with a reduction in pulmonary complications. As a component of enhanced recovery pathways, intercostal nerve blocks with liposomal bupivacaine are increasingly utilized, but the extent to which this element may contribute to such outcomes has not been evaluated., Methods: Patients undergoing lung resection for stage I to III non-small cell lung cancer at a single institution from 2006 to 2017 were examined for major postoperative pulmonary morbidity, defined as pneumonia, acute respiratory distress syndrome, respiratory arrest, reintubation, bronchoscopy, or need for discharge with oxygen. Pharmacy records were queried for administration of liposomal bupivacaine via posterior intercostal nerve block. Patients treated with and without liposomal bupivacaine were compared in a logistic regression to determine the impact on pulmonary morbidity., Results: A total of 2865 patients were identified, including 860 (30%) who were treated with liposomal bupivacaine via posterior intercostal block. Pulmonary morbidity occurred in 455 (16%). Adoption of liposomal bupivacaine analgesia occurred over several years, beginning in 2012 to full adoption by 2017. Liposomal bupivacaine management was associated with a reduction in pulmonary complications, as compared with nonuse (odds ratio, 0.63; P = .006). Additional factors associated with the occurrence of pulmonary morbidity were age, body mass index, smoking, spirometry values, and operative blood loss., Conclusions: As a component of an active enhanced recovery program, liposomal bupivacaine is associated with a reduction in major pulmonary complications, and utilization should be evaluated on a hospital-by-hospital basis., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Although colorectal cancer bowel segment location has been shown to independently predict the outcomes in early stage disease, it has not been previously studied in the setting of pulmonary metastases. We sought to determine whether colorectal cancer location affects survival after pulmonary metastasectomy., Methods: Patients who had undergone pulmonary metastasectomy for colorectal cancer at a single institution from 2011 to 2018 were reviewed. Univariable and multivariable Cox regression analyses were performed to identify predictors of overall survival and disease-free survival. The Kaplan-Meier survival method was used to determine differences between groups., Results: A total of 194 patients were evaluated. The median follow-up, survival time, and 5-year survival rate were 36.8 months, 75.8 months, and 57%, respectively, and 122 patients (63%) had experienced disease recurrence at any location. On univariable analysis, age, primary tumor location, pulmonary nodule size, ≥3 pulmonary nodules, and intrathoracic nodal disease were associated with overall survival. On multivariable analysis, patients with left-sided tumors experienced a survival benefit (hazard ratio, 0.31; P = .036). Kaplan-Meier analysis revealed a median survival time of 90 months (95% confidence interval, 82 months to not reached) compared with 55 months (95% confidence interval, 49 months to not reached) for patients with left-sided and rectal tumors, respectively, after metastasectomy (P = .078). Location was not associated with disease-free survival on Cox multivariable regression., Conclusions: We found that left-sided colorectal cancer is associated with prolonged survival after pulmonary metastasectomy. Future investigations are required to determine the validity of such findings, including the effect of location in the prognostication for patients who are candidates for pulmonary metastasectomy., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Surgeons have shifted away from the practice of en bloc esophagectomy, particularly in the era of neoadjuvant therapies. Although some still advocate for this radical approach, contemporary data establishing its superiority are sparse. We hypothesized that a more complete, radical resection could be completed in the setting of chemoradiation without adding morbidity., Methods: Patients undergoing esophagectomy after neoadjuvant chemoradiation for esophageal adenocarcinoma from 2006-2018 were evaluated. Outcomes after right transthoracic en bloc esophagectomy were compared with standard esophagectomy to determine the impact on outcomes. A Cox proportional hazard model was evaluated, and logistic regression was performed to determine the impact of en bloc resection on postoperative morbidity., Results: A total of 604 patients were identified, including 133 (22%) who underwent modified en bloc esophagectomy. Positive margins were most likely to occur in standard esophagectomy (35 of 471, 7%) vs en bloc (3 of 133, 2%) (P = .026). En bloc resection yielded a greater lymph node harvest (27; interquartile range, 22-36), as compared to standard esophagectomy (22; interquartile range, 17-28), P < .001. Multivariable analysis demonstrated prolonged progression-free survival with en bloc resection (hazard ratio, 0.74; P = .041), with 3-year freedom from locoregional recurrences of 78% and 90% for standard and en bloc approaches (P = .044). There were no differences in cardiopulmonary, gastrointestinal, or wound complications, as well as leak or chylothorax., Conclusions: Our experience demonstrates improved locoregional disease control with en bloc esophagectomy, with equivalent morbidity. Although these results may be multifactorial, including adequate clearance of both primary tumor and nodal micrometastases, this approach is safe and feasible., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Comprehensive local consolidative therapy led to improved overall survival in oligometastatic non-small cell lung cancer in a recent phase II trial, yet the role of pulmonary resection in ongoing oligometastatic trials is a matter of controversy. We sought to examine outcomes after pulmonary resection with radiotherapy used as a benchmark comparator., Methods: Patients treated at a single institution (2000-2017) with cT1-3N0-2M1 non-small cell lung cancer, 3 or less synchronous metastases, and performance status 0 to 1, and who received comprehensive local consolidative therapy were analyzed according to local consolidative therapy modality for the primary lesion. Progression was analyzed with death as a competing risk., Results: Of 88 patients meeting inclusion criteria, 63 (71.6%) received radiotherapy for local consolidative therapy modality for the primary lesion and 25 (28.4%) underwent surgery (lobectomy 20/25 [80.0%], pneumonectomy 3/25 [12.0%], sublobar 2/25 [8.0%]). Time from diagnosis to local consolidative therapy modality for the primary lesion was similar. Surgical patients were younger and had lower intrathoracic disease burden. Ninety-day post-treatment mortality was low (surgery 0/25 [0.0%], radiotherapy 1/63 [1.6%]). Median postoperative survival time was 55.2 months (95% confidence interval, 20.1 to not reached), with 1- and 5-year overall survivals of 95.7% and 48.0%, respectively. After radiotherapy, median postoperative survival time was 23.4 months (confidence interval, 17.2-35.9); 1- and 5-year overall survivals were 74.3% and 24.2%, respectively. No differences were observed between modalities in site of first failure, cumulative incidence of locoregional failure (P = .635), or systemic progression (P = .747)., Conclusions: Pulmonary resection is feasible and associated with long-term survival in selected patients with synchronous oligometastatic non-small cell lung cancer. Surgery should remain a local consolidative therapeutic option for patients with operable oligometastatic non-small cell lung cancer enrolled in ongoing and future randomized clinical trials., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: As strategies promoting enhanced recovery protocols and opioid minimization techniques are increasingly prioritized, use of nonsteroidal antiinflammatory drugs continues to rise. Whether this prevalent use poses increased risk for bleeding or renal dysfunction in surgical populations after extensive dissection and fluid shifts is unclear., Methods: We reviewed records of patients undergoing esophagectomy for a diagnosis of esophageal adenocarcinoma at a single institution from 2006 to 2018 for ketorolac administration during the postoperative hospital admission, as well as the occurrence of postoperative events, defined as the need for blood product transfusion and/or acute kidney injury., Results: We identified 1019 patients, 123 of whom experienced postoperative events (12%). Ketorolac was administered to 686 (67%). Furthermore, ketorolac use steadily increased over the study period; 36 of 72 patients received this medication in 2006 (49%), and 76 of 83 in 2018 (92%). Multivariable logistic regression failed to identify a relationship between ketorolac administration (assessed as a binary covariate) and postoperative events (P = .657). Additional examination for a dose-response relationship using the cumulative total dose from the time of surgery to discharge also did not demonstrate a relationship with postoperative events (P = .829). In an effort to evaluate a more homogeneous population, we performed a subgroup analysis using only patients treated with trimodality therapy, which showed similar findings., Conclusions: Ketorolac has become a staple of multimodal postesophagectomy analgesic regimens. Importantly, this medication does not pose risk for acute kidney injury or bleeding after surgery., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Recent evidence has shown an association between postoperative ketorolac use and anastomotic leak in patients undergoing intestinal and colorectal operations, but this relationship has been minimally explored after esophagectomy. As the use of nonopioid pain control and enhanced recovery protocols is increasingly prioritized, determination of a possible correlation between perioperative ketorolac use and leak is essential., Methods: Records of patients undergoing esophagectomy for adenocarcinoma at a single institution from 2006 to 2018 reviewed for occurrence of anastomotic leak. Institutional pharmacy records were queried for ketorolac administration during the surgical case through the time of discharge. Multivariable logistic regression was used to determine the relationship between ketorolac administration and anastomotic leak., Results: A total of 1019 patients met inclusion criteria, the majority of whom were male (907, 89%) with a median age of 62 years. Patients predominantly presented with locoregionally advanced disease and were treated with initial chemoradiation. Ketorolac was administered to 686 patients (67%); use was observed to increase over the study period from 49% in 2006 to 92% in 2016. Conversely, anastomotic leak occurred in 87 patients (9%) overall and decreased over time from 15% (11/72) in 2006 to 2% (2/83) in 2018. Upon multivariable analysis, neither ketorolac administration evaluated as a categoric variable (odds ratio, 0.99; P = .958) or as a continuous variable using dose (odds ratio, 1.00; P = .843) demonstrated an association with anastomotic leak., Conclusions: Ketorolac in the postoperative period after esophagectomy has become an integral component of enhanced recovery pathways and does not appear to be associated with anastomotic leak., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Major pathological response (MPR) is prognostic of outcomes for patients with non-small-cell lung cancer following neoadjuvant chemotherapy and is used as the primary end point in neoadjuvant immunotherapy trials. We studied the influence of pathological nodal disease on patterns and timing of recurrence among patients with MPR., Methods: Patients treated with neoadjuvant chemotherapy for stages I-III non-small-cell lung cancer were identified. Surgical specimens were histopathologically examined for tumour viability, categorized as ≤10% viability (MPR) or >10% (NoMPR). Overall survival and disease-free survival were evaluated with emphasis upon MPR and pathological nodal disease., Results: Among 307 patients, 58 (19%) had MPR within primary tumour and 42 (14%) had MPRypN0. In the MPR group, the frequency of cN0 and cN+ disease was 18 (31%) and 40 (69%); similarly, the frequency of ypN0, ypN1 and ypN2 was 72% (42/58), 16% (9/58) and 12% (7/58), respectively. When evaluating only those with MPR, recurrence rates among those with MPRypN0, MPRypN1 and MPRypN2 were 33% (14/42), 44% (4/9) and 71% (5/7) (P = 0.16). The median time-to-recurrence in MPRypN0, MPRypN1 and MPRypN2 was 40, 10 and 14 months (P = 0.006). Distant recurrences were less common among those with MPRypN0 [MPRypN0, 26% (11/42); MPRypN1, 44% (4/9); MPRypN2, 71% (5/7); P = 0.047]. Though the median disease-free survival was prolonged among those with MPR vs NoMPR (120 vs 25 months, P < 0.0001), only those with MPRypN0 had prolonged disease-free survival in comparison to other groups upon pairwise comparisons, while MPRypN+ experienced no benefit., Conclusions: MPRypN0 represents the most favourable surrogate end point following neoadjuvant chemotherapy. Patients with ypN1-2 are at the risk of early recurrence regardless of primary tumour MPR, warranting intensive surveillance and consideration for additional adjuvant therapy. We highlight that MPRypN0 is the most rigorous end point and should be considered as a surrogate end point in future neoadjuvant trials., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Social media serves as a tool to fill gaps in current efforts to promote women in cardiothoracic surgery, and, given its global reach, may be a particularly effective modality. Social media has an important role in networking and mentorship, especially for women seeking careers in specialties with relatively sparse female representation, such as cardiothoracic surgery. In addition, social media may facilitate professional interactions, collaboration, growth of online reputations, engagement in continued education, communication of novel research findings, and patient education. Herein, we review the evidence for social media in the networking and mentorship of women in cardiothoracic surgery. Future studies are needed to establish the durability of social media efforts and predictors in its effectiveness in achieving its goals., Competing Interests: Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.04.11). The series “Women in Thoracic Surgery” was commissioned by the editorial office without any funding or sponsorship. MA serves as an unpaid editorial board member of Journal of Thoracic Disease from Aug 2019 to Jul 2021. The authors have no other conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Introduction: The combination of programmed cell death protein-1 or programmed death-ligand 1 immune checkpoint blockade and chemotherapy has revolutionized the treatment of advanced NSCLC, but the mechanisms underlying this synergy remain incompletely understood. In this study, we explored the relationships between neoadjuvant chemotherapy and the immune microenvironment (IME) of resectable NSCLC to identify novel mechanisms by which chemotherapy may enhance the effect of immune checkpoint blockade., Methods: Genomic, transcriptomic, and immune profiling data of 511 patients treated with neoadjuvant chemotherapy followed by surgery (NCT) versus upfront surgery (US) were compared with determined differential characteristics of the IMEs derived from whole-exome sequencing (NCT = 18; US = 73), RNA microarray (NCT = 45; US = 202), flow cytometry (NCT = 17; US = 39), multiplex immunofluorescence (NCT = 10; US = 72), T-cell receptor sequencing (NCT = 16 and US = 63), and circulating cytokines (NCT = 18; US = 73)., Results: NCT was associated with increased infiltration of cytotoxic CD8 + T cells and CD20 + B cells. Moreover, NCT was associated with increases in CD8 + CD103 + and CD4 + CD103 + PD-1 + TIM3 - tissue resident memory T cells. Gene expression profiling supported memory function of CD8 + and CD4 + T cells. However, NCT did not affect T-cell receptor clonality, richness, or tumor mutational burden. Finally, NCT was associated with decreased plasma BDNF (TrkB) at baseline and week 4 after surgery., Conclusions: Our study supports that, in the context of resectable NSCLC, neoadjuvant chemotherapy promotes antitumor immunity through T and B cell recruitment in the IME and through a phenotypic change toward cytotoxic and memory CD8 + and CD4 + memory helper T cells., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Mutations in the serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) have been implicated in mediating resistance to checkpoint blockade among patients with advanced lung adenocarcinoma. We sought to examine the associations between clinicopathologic characteristics, tumor LKB1 expression, features of the immune microenvironment, and postoperative prognosis among patients with early stage lung adenocarcinoma undergoing surgical therapy., Methods: Formalin-fixed, paraffin-embedded specimens of patients undergoing resection of stage I to III, chemotherapy-naïve adenocarcinomas (1997 to 2008) were analyzed using tissue microarray sectioning. Sublobar resections were excluded. Intratumoral LKB1/STK11 expression was quantified as H-score. In a subset, tumor-associated immune cell populations were quantified using whole tumor sections in peritumoral and intratumoral compartments., Results: In all, 104 patients met inclusion criteria. Expression of LKB1/STK11 (median H-score 102.9) was higher in women (median 123.3) than in men (100, P = .004) and in never-smokers (median 145) than in former/current smokers (100, P = .002). Expression of LKB1/STK11 was positively correlated with intratumoral infiltration of cluster of differentiation (CD) 3 + (r = 0.351, P = .005), CD4 + (r = 0.436, P < .001), and CD8 + (r = 0.263, P = .049) cells. Patients with extrathoracic recurrence had lower tumor expression of LKB1/STK11 than did other patients with recurrent disease. On multivariate analysis, low LKB1/STK11 expression remained independently associated with poor disease-free survival and distant disease-free survival., Conclusions: Low LKB1/STK11 expression is associated with specific patient characteristics and poor postoperative prognosis in chemotherapy-naïve lung adenocarcinoma. Further investigation is warranted to delineate its clinical significance in the context of evaluating novel therapeutic agents in patients with resectable disease., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes., Methods: Records of patients who presented with stage IVA thymic neoplasms from 2000 to 2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival., Results: Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%)., Conclusions: Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed., (© 2020 Wiley Periodicals LLC.)

Background: The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early-stage (stage I and II) non-small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS)., Methods: We identified surgically resected early-stage NSCLC between 1998 and 2016. The 3-year OS (1998-2014) and 5-year OS (1998-2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS., Results: There was a significant upward trend in the 3-year (1998, 56%; 2014, 83%; APC = 1.8) and 5-year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack-years; high-grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS., Conclusion: The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early-stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes., (© 2020 Wiley Periodicals, Inc.)

Objectives: The influence of surgical approach on systemic inflammatory response and the subsequent oncologic impact for non-small cell lung cancer is debated. We aimed to measure the effects of thoracic surgical approach on peripheral cytokine milieu over time., Methods: Patients undergoing primary lung resection without neoadjuvant therapy (2016-2018) were evaluated. A panel of 43 cytokines, angiogenic factors, and inflammatory molecules (CAFs) were evaluated in peripheral blood preoperatively, at 24 -hs and 4-weeks postoperatively. Differences between CAFs in patients undergoing thoracotomy versus video-assisted thoracoscopic surgery (VATS) at all timepoints were assessed using Student's t-test., Results: 76 patients with available peripheral CAF panels met inclusion criteria. Thoracotomy was performed in 53 (70 %) patients while VATS was undertaken in 23 (30 %). Upon examination of known inflammatory CAFs, including IL-1β, IL-6, IL-8, IL-10, IFN-γ, and soluble (s) CD27, no differences were detected at 24 h or 4 weeks postoperatively between surgical groups. Examination of trends over time did not demonstrate any temporal derangements for these CAFs, with return to baseline levels by 4 weeks postoperatively for both groups. Evaluation of soluble (s) checkpoint molecules, including sPD-1, sPD-L1, sTIM-3, and sCTLA-4, did not reveal any differences in the immediate postoperative or long-term recovery period., Conclusions: Peripheral immune profiles following pulmonary resection do not appear to differ between VATS and thoracotomy postoperatively. CAF fluctuations are transient and recover rapidly. These results, at the peripheral cytokine level, suggest that the surgical approach for lung cancer is unlikely to alter the effectiveness of novel immune-modulating systemic therapies, although more studies are needed to validate these findings., Competing Interests: Declaration of Competing Interest Dr. Swisher discloses a financial relationship with Ethicon and the Peter MacCallum Cancer Center; Dr. Cascone with the Society for Immunotherapy of Cancer and Bristol-Myers Squibb; Dr. Sepesi with Bristol-Myers Squibb; Dr. Heymach with AstraZeneca, Boehringer Ingelheim, Exelixis, Genentech, GlaxoSmithKline, Guardant Health, Hengrui, Lilly, Novartis, Spectrum, EMD Serono, and Synta; Dr. Gibbons with AstraZeneca and Sanofi; and Dr. Jianjun Zhang with BMS, AstraZeneca, Geneplus, OrigMed, Innovent, Merck, and Johnson & Johnson. Dr. Gibbons has received research funding from AstraZeneca, Janssen, and Takeda. Dr. Heymach has received research support from AstraZeneca, Bayer, GlaxoSmithKline, and Spectrum. Dr. Cascone has received research funding to MD Anderson Cancer Center from Boehringer Ingelheim and Bristol-Myers Squibb., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Whether dosimetric advantages of proton beam therapy (PBT) translate to improved clinical outcomes compared with intensity-modulated radiation therapy (IMRT) remains unclear. This randomized trial compared total toxicity burden (TTB) and progression-free survival (PFS) between these modalities for esophageal cancer., Methods: This phase IIB trial randomly assigned patients to PBT or IMRT (50.4 Gy), stratified for histology, resectability, induction chemotherapy, and stage. The prespecified coprimary end points were TTB and PFS. TTB, a composite score of 11 distinct adverse events (AEs), including common toxicities as well as postoperative complications (POCs) in operated patients, quantified the extent of AE severity experienced over the duration of 1 year following treatment. The trial was conducted using Bayesian group sequential design with three planned interim analyses at 33%, 50%, and 67% of expected accrual (adjusted for follow-up)., Results: This trial (commenced April 2012) was approved for closure and analysis upon activation of NRG-GI006 in March 2019, which occurred immediately prior to the planned 67% interim analysis. Altogether, 145 patients were randomly assigned (72 IMRT, 73 PBT), and 107 patients (61 IMRT, 46 PBT) were evaluable. Median follow-up was 44.1 months. Fifty-one patients (30 IMRT, 21 PBT) underwent esophagectomy; 80% of PBT was passive scattering. The posterior mean TTB was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than PBT (17.4; 10.5-25.0). The mean POC score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2). The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial's stopping boundary of 0.9942 at the 67% interim analysis. The 3-year PFS rate (50.8% v 51.2%) and 3-year overall survival rates (44.5% v 44.5%) were similar., Conclusion: For locally advanced esophageal cancer, PBT reduced the risk and severity of AEs compared with IMRT while maintaining similar PFS.

Background: Multiple synchronous lung tumors (MSLT), particularly within a single lobe, represent a diagnostic and treatment challenge. While histologic assessment was once the only method to possibly distinguish multiple primary lung cancers, there is a growing interest in identifying unique genomic features or mutations to best characterize these processes., Methods: In order to differentiate multiple primary lung malignancies from intrapulmonary metastases in patients with MSLT, we performed whole exome sequencing (WES) on 10 tumor samples from 4 patients with MSLT., Results: Shared mutations between tumors from the same patient varied from 0-91%. Patient 3 shared no common mutations; however, in Patients 2 and 4, identical mutations were identified among all tumors from each patient, suggesting that the three tumors identified in Patient 3 represent separate primary lung cancers, while those of Patients 1, 2 and 4 signify hematogenous and lymphatic spread., Conclusions: A high proportion of shared mutations between different lung tumors is likely indicative of intrapulmonary metastatic disease, while tumors with distinct genomic profiles likely represent multiple primary malignancies driven by distinct molecular events. Application of genomic profiling in the clinical setting may prove to be important to precise management of patients with MSLT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1). CG has a patent named “Markers associated with ribavirin-induced anemia” that was issued in 2012. CB and IIW report grants and personal fees from Genentech/Roche, grants and personal fees from Bayer, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from AstraZeneca/Medimmune, grants and personal fees from Pfizer, grants and personal fees from HTG Molecular, grants and personal fees from Merck, personal fees from GlaxoSmithKline, grants and personal fees from Guardant Health, personal fees from MSD, grants from Oncoplex, grants from DepArray, grants from Adaptive, grants from Adaptimmune, grants from EMD Serono, grants from Takeda, grants from Amgen, grants from Karus, grants from Johnson & Johnson, grants from Iovance, grants from 4D, grants from Novartis, grants from Oncocyte, grants from Akoya, outside the submitted work. JVH reports grants and other from AstraZeneca, other from Bristol-Myers Squibb, other from GlaxoSmithKline, other from Kairos Venture Investments, other from BrightPath Therapeutics, other from Hengrui Therapeutics, other from Eli Lilly, other from EMD Serono, grants and personal fees from Spectrum, other from Foundation One Medicine, grants from NIH/NCI, grants from American Cancer Society, grants from Checkmate Pharmaceuticals, outside the submitted work. Jianjun Z reports grants from Merck, grants from Johnson and Johnson, personal fees from BMS, personal fees from AZ, personal fees from GenePlus, personal fees from Innovent, outside the submitted work. MBA serves as an unpaid editorial board member of Journal of Thoracic Disease from Aug 2019 to Jul 2021. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background and Objectives: Precision medicine has altered the management of colorectal cancer (CRC). However, the concordance of mutational findings between primary CRC tumors and associated pulmonary metastases (PM) is not well-described. This study aims to determine the concordance of genomic profiles between primary CRC and PM., Methods: Patients treated for colorectal PM at a single institution from 2000 to 2017 were identified. Mutational concordance was defined as either both wild-type or both mutant alleles in lung and colorectal lesion; genes with opposing mutational profiles were reported as discordant., Results: Thirty-eight patients met inclusion criteria, among whom KRAS, BRAF, NRAS, MET, RET, and PIK3CA were examined for concordance. High concordance was demonstrated among all evaluated genes, ranging from 86% (KRAS) to 100% concordance (NRAS, RET, and MET). De novo KRAS mutations were detected in the PM of 4 from 35 (11%) patients, 3 of whom had previously received anti-epidermal growth factor receptor (EGFR) therapy. Evaluation of Cohen's κ statistic demonstrated moderate to perfect correlation among evaluated genes., Conclusions: Because high intertumoral genomic homogeneity exists, it may be reasonable to use primary CRC mutational profiles to guide prognostication and targeted therapy for PM. However, the possibility of de novo KRAS-mutant PM should be considered, particularly among patients previously treated with anti-EGFR therapy., (© 2020 Wiley Periodicals, Inc.)

Background: The biological underpinnings of the prognostic and predictive significance of a relative neutrophilia in patients with non-small lung cancer (NSCLC) are undefined. We sought to comprehensively examine the relationships between circulating and intratumoral neutrophil populations and features of the immune contexture in patients undergoing NSCLC resection., Methods: Preoperative soluble cytokine and angiogenic factors; tumor multiplex immunofluorescence; RNA, whole exome, and T-cell receptor sequencing; and flow cytometry were analyzed for relationships with populations of circulating (from complete blood counts) and intratumoral neutrophils (transcriptional signatures) in a prospectively enrolled resected NSCLC cohort (n=66). In a historical cohort (n=1524), preoperative circulating neutrophil and lymphocyte counts were analyzed for associations with overall survival (OS)., Results: Circulating neutrophil populations were positively correlated with increased tumor burden, and surgical tumor resection was followed by a subsequent reduction in peripheral neutrophil counts. Expansion of the circulating neutrophil compartment was associated with increased levels of pro-granulopoietic (IL-1β, IL-17A, TNFα, IL-6) and T H 2-associated (IL-5, IL-13) cytokines. Tumors with high intratumoral neutrophil burden were marked by a blunted T-cell response characterized by reduced expression of cytotoxic T-cell genes ( CD8A , CD8B , GZMA , GZMB ), decreased CD3 + CD8 + cell infiltration, and diminished expression of IFNγ-related genes. The associations between increased intratumoral neutrophil burden and reduced CD3 + CD8 + infiltration persisted after adjustment for tumor size, histology, mutational burden, and PD-L1 expression. In 1524 patients, elevated preoperative circulating neutrophil count was independently associated with worse OS (main effect HR 1.82, 95% CI 1.24 to 2.68, p=0.002)., Conclusions: Our findings demonstrate that neutrophil expansion reflects protumorigenic and immunosuppressive processes that manifest as worse OS in patients undergoing NSCLC resection. These results justify further investigation of therapeutic strategies targeting neutrophil-associated immune evasion., Competing Interests: Competing interests: DLG has received research funding from AstraZeneca, Janssen, and Takeda and has participated in advisory boards for AstraZeneca and Sanofi. SGS has participated in advisory committees for Ethicon and for the Peter MacCallum Cancer Center. JVH has received research support from AstraZeneca, Bayer, GlaxoSmithKline, and Spectrum; participated in advisory committees for AstraZeneca, Boehringer Ingelheim, Exelixis, Genentech, GlaxoSmithKline, Guardant Health, Hengrui, Lilly, Novartis, Specrtum, EMD Serono, and Synta; and received royalties and/or licensing fees from Spectrum. TC has received speaker’s fees from the Society for Immunotherapy of Cancer and Bristol-Myers Squibb and research funding to MD Anderson Cancer Center from Boehringer Ingelheim and Bristol-Myers Squibb. JZ served on advisory board for AstraZeneca and Geneplus and received speaker’s fees from BMS, Geneplus, OrigMed, Innovent, grant from Merck, outside the submitted work. BS receives consultation fees from Bristol-Myers Squibb. No potential conflicts of interest are disclosed by the other authors., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Although in-training examinations provide surrogate data on qualifying exam readiness, use of mock oral examinations (MOEs) in cardiothoracic surgery training before the American Board of Thoracic Surgery certifying oral exam is not uniform. Although MOEs are prioritized by some institutions, development and execution of these labor-intensive, time-consuming exams may be a barrier to others. Therefore, we aimed to develop an MOE program and to assess its educational value., Methods: We developed an institutional MOE program that mimicked the certification examination and was serially administered to 10 cardiothoracic surgery trainees from 2014 to 2018. Biannual MOE scores were reviewed, along with certifying examination pass rates. MOE data were available for curriculum development and trainee performance evaluations., Results: MOEs were conducted twice each academic year, with 4 exams administered during each individual's training. MOE program development required significant up-front time commitment, and thereafter each MOE required approximately 24 total faculty hours and 4 administrator hours. The pass rates for sequential MOEs demonstrated gradual improvement, and the corresponding certifying exam pass rate was 100% for these same individuals. MOE data were routinely used for curriculum refinement, as well as individual trainee feedback., Conclusions: Standardized MOEs are useful educational adjuncts to assess trainees' knowledge and readiness for certification exams, but require significant coordination and time to develop an accurate, rigorous simulation mechanism. Although we recognize that improvement in serial MOEs is likely related to exposure as well as expanding funds of knowledge, we believe these results justify use of this assessment tool in training., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)