Identifying Molecular Pathophysiology and Potential Therapeutic Options in Iatrogenic Tracheal Stenosis.

INTRODUCTION: While most patients with iatrogenic tracheal stenosis (ITS) respond to endoscopic ablative procedures, approximately 15% experience a recalcitrant, recurring disease course that is resistant to conventional management. We aimed to explore genetic profiles of patients with recalcitrant ITS to understand underlying pathophysiology and identify novel therapeutic options. METHODS: We collected 11 samples of granulation tissue from patients with ITS and performed RNA sequencing. We identified the top 10 most highly up- and down-regulated genes and cellular processes that these genes corresponded to. For the most highly dysregulated genes, we identified potential therapeutic options that favorably regulate their expression. RESULTS: The dysregulations in gene expression corresponded to hyperkeratinization (upregulation of genes involved in keratin production and keratinocyte differentiation) and cellular proliferation (downregulation of cell cycle regulating and pro-apoptotic genes). Genes involved in retinoic acid (RA) metabolism and signaling were dysregulated in a pattern suggesting local cellular RA deficiency. Consequently, RA also emerged as the most promising potential therapeutic option for ITS, as it favorably regulated seven of the ten most highly dysregulated genes. CONCLUSION: This is the first study to characterize the role of hyperkeratinization and dysregulations in RA metabolism and signaling in the disease pathophysiology. Given the ability of RA to favorably regulate key genes involved in ITS, future studies must explore its efficacy as a potential therapeutic option for patients with recalcitrant ITS.

Gene expression profiles in COVID-19-associated tracheal stenosis indicate persistent anti-viral response and dysregulated retinol metabolism.

INTRODUCTION: Coronavirus disease 2019 (COVID-19)-associated tracheal stenosis (COATS) may occur as a result of prolonged intubation during COVID-19 infection. We aimed to investigate patterns of gene expression in the tracheal granulation tissue of patients with COATS, leverage gene expression data to identify dysregulated cellular pathways and processes, and discuss potential therapeutic options based on the identified gene expression profiles. METHODS: Adult patients (age ≥ 18 years) presenting to clinics for management of severe, recalcitrant COATS were included in this study. RNA sequencing and differential gene expression analysis was performed with transcriptomic data for normal tracheal tissue being used as a control. The top ten most highly upregulated and downregulated genes were identified. For each of these pathologically dysregulated genes, we identified key cellular pathways and processes they are involved in using Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) applied via Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: Two women, aged 36 years and 37 years, were included. The profile of dysregulated genes indicated a cellular response consistent with viral infection (CXCL11, PI15, CCL8, DEFB103A, IFI6, ACOD1, and DEFB4A) and hyperproliferation/hypergranulation (MMP3, CASP14 and HAS1), while downregulated pathways included retinol metabolism (ALDH1A2, RBP1, RBP4, CRABP1 and CRABP2). CONCLUSION: Gene expression changes consistent with persistent viral infection and dysregulated retinol metabolism may promote tracheal hypergranulation and hyperproliferation leading to COATS. Given the presence of existing literature highlighting retinoic acid's ability to favorably regulate these genes, improve cell-cell adhesion, and decrease overall disease severity in COVID-19, future studies must evaluate its utility for adjunctive management of COATS in animal models and clinical settings.

Novel Journal Metrics in Cardiothoracic Surgery: How Different Are Contemporary Metrics From the Impact Factor?

OBJECTIVE: Despite shortcomings, impact factor (IF) remains the "gold standard" metric for journal quality. However, novel metrics including the h-index, g-index, and Altmetric Attention Score (AAS; mentions in mainstream/social media) are gaining traction. We assessed correlations between these metrics among cardiothoracic surgery journals. METHODS: For all cardiothoracic surgery journals with a 2021 Clarivate IF (N = 20), the 2-year IF (2019 to 2020) and 5-year IF (2016 to 2020), h-index, and g-index were obtained. Two-year journal-level AAS (2019 to 2020) was also calculated. Journal Twitter presence and activity was sourced from Twitter and the Twitter application programming interface. Correlations were assessed using Spearman correlation, and coefficients of determination were calculated. RESULTS: IF demonstrated a moderate-strong positive correlation with the h-index (rs = 0.48 to 0.77) and g-index (rs = 0.49 to 0.79) and a moderate correlation with AAS (rs = 0.53 to 0.58). The 2-year IF accounted for 25% to 49% of variability in the h-index, 27% to 55% of variability in the g-index, and 32% of variability in the AAS. Among journals with a Twitter account (N = 10), IF was strongly correlated with Twitter following (rs = 0.81 to 0.86), which was in turn strongly correlated with journal AAS (rs = 0.79). Article-level AAS was moderately correlated with citation count (rs = 0.47). CONCLUSIONS: IF accounted for only between 25% and 55% of variability in the h-index and g-index, indicating that these newer metrics measure unique dimensions of citation-based impact. Thus, the academic community must familiarize itself with these newer journal metrics. Social media attention may be associated with scholarly impact, although further work is needed to understand these relationships.

Factors associated with safe and successful postoperative day 1 discharge after lung operations: a systematic review and meta-analysis.

BACKGROUND: A shorter length of stay (LOS) is associated with fewer hospital-acquired adverse conditions and decreased utilization of hospital resources. While modern perioperative care protocols have enabled some ambitious surgical teams to achieve discharge as early as within postoperative day 1 (POD1), most other teams remain cautious about such an approach due to the perceived risk of missing postoperative complications and increased readmission rates. We aimed to identify factors that would help guide surgical teams aiming for safe and successful POD1 discharge after lung resection. METHODS: We searched the PubMed, Embase, Scopus, Web of Science and CENTRAL databases for articles comparing perioperative characteristics in patients discharged within POD1 (DWPOD1) and after POD1 (DAPOD1) following lung resection. Meta-analysis was performed using a random-effects model. RESULTS: We included eight retrospective cohort studies with a total of 216,887 patients, of which 22,250 (10.3%) patients were DWPOD1. Our meta-analysis showed that younger patients, those without cardiovascular and respiratory comorbidities, and those with better preoperative pulmonary function are more likely to qualify for DWPOD1. Certain operative factors, such as a minimally invasive approach, shorter operations, and sublobar resections, also favor DWPOD1. DWPOD1 appears to be safe, with comparable 30-day mortality and readmission rates, and significantly less postoperative morbidity than DAPOD1. CONCLUSIONS: In select patients with a favorable preoperative profile, DWPOD1 after lung resection can be achieved successfully and without increased risk of adverse outcomes such as postoperative morbidity, mortality, or readmissions.

Neoadjuvant vs Adjuvant Chemoimmunotherapy for Stage II-IIIB Non-Small Cell Lung Cancer.

BACKGROUND: In patients with resectable non-small cell lung cancer (NSCLC), recent trials demonstrate survival benefit of chemoimmunotherapy over chemotherapy alone in both the neoadjuvant and adjuvant settings. To date, there is no direct comparison between neoadjuvant and adjuvant protocols. We compared neoadjuvant vs adjuvant chemoimmunotherapy for resectable stage II-IIIB NSCLC. METHODS: We queried the National Cancer Database for patients who had undergone an operation for stage II-IIIB NSCLC and who had received neoadjuvant or adjuvant chemoimmunotherapy between 2015 and 2020. We used inverse probability weighting to adjust for confounding variables and used Kaplan-Meier survival curves and Cox regression to explore the relationship between treatment groups and overall survival (OS) at 3 years postoperatively. RESULTS: The inverse probability-weighted cohort represented 2119 weighted patient cases (neoadjuvant, 1034; adjuvant, 1085). Kaplan-Meier analysis demonstrated a significant OS benefit for neoadjuvant chemoimmunotherapy compared with adjuvant chemoimmunotherapy in the weighted cohort (3-year OS: 77% [95% CI, 71%-83%] vs 68% [95% CI, 64%-72%]; P = .035). On adjusted Cox regression, neoadjuvant chemoimmunotherapy was associated with a significant OS benefit (hazard ratio, 0.70; 95% CI, 0.50-0.96; P = .027). Among patients for whom pathologic stage data were available, 25% of patients receiving neoadjuvant chemoimmunotherapy had a pathologic complete response, with an additional 32.5% being downstaged. CONCLUSIONS: Neoadjuvant chemoimmunotherapy confers a significant OS benefit over adjuvant chemoimmunotherapy for patients with resectable stage II-IIIB NSCLC. Although randomized trials are needed to confirm our findings, strong consideration should be given to administering neoadjuvant chemoimmunotherapy to patients who are predetermined to receive systemic treatment.

Impact of facility type and volume in locally advanced esophageal cancer.

BACKGROUND: We hypothesized that academic facilities and high-volume facilities would be independently associated with improved survival and a greater propensity for performing surgery in locally advanced esophageal cancer. METHODS: We identified patients diagnosed with stage IB-III esophageal cancer during 2004-2016 from the National Cancer Database. Facility type was categorized as academic or community, and facility volume was based on the number of times a facility's unique identification code appeared in the dataset. Each facility type was dichotomized into high- and low-volume subgroups using the cutoff of 20 esophageal cancers treated/year. We fitted multivariable regression models in order to assess differences in surgery selection and survival between facilities according to type and volume. RESULTS: Compared to patients treated at high-volume community hospitals, those at high-volume academic facilities were more likely to undergo surgery (odds ratio: 1.865, p < 0.001) and were associated with lower odds of death (odds ratio: 0.784, p = 0.004). For both academic and community hospitals, patients at high-volume facilities were more likely to undergo surgery compared to those at low-volume facilities, p < 0.05. For patients treated at academic facilities, high-volume facilities were associated with lower odds of death (odds ratio: 0.858, p = 0.02) compared to low-volume facilities, while there was no significant difference in the odds of death between high- and low-volume community hospitals (odds ratio: 1.018, p = 0.87). CONCLUSIONS: Both facility type and case volume impact surgery selection and survival in locally advanced esophageal cancer. Compared to community hospitals, academic facilities were more likely to perform surgery and were associated with improved survival.

From emissions to incisions and beyond: the repercussions of climate change on surgical disease in low- and-middle-income countries.

Climate change has far-reaching repercussions for surgical healthcare in low- and middle-income countries. Natural disasters cause injuries and infrastructural damage, while air pollution and global warming may increase surgical disease and predispose to worse outcomes. Socioeconomic ramifications further strain healthcare systems, highlighting the need for integrated climate and healthcare policies.

Anastomotic stenosis of bioengineered trachea grafts is driven by transforming growth factor ß1-induced signaling, proinflammatory macrophages, and delayed epithelialization.

Objective: Anastomotic stenosis caused by hypertrophic granulation tissue often develops in response to orthotopically implanted bioengineered tracheal grafts. To determine mechanisms responsible for the development and persistence of this granulation tissue, we looked for changes in gene expression from tissue specimens from the graft-native interface. Methods: RNA was isolated from paraffin-embedded tissue samples of the anastomotic sites of orthotopically implanted bioengineered tracheal grafts of 9 animals. Tissue samples were binned into 3 groups based on degree of stenosis: no stenosis (<5%), mild stenosis (25%-50%), and moderate and severe stenosis (≥75%). Sections of healthy trachea tissue were used as control. The expression levels of ∼200 genes related to wound healing, plus several endogenous controls, were measured with a pathway-focused predesigned primer array. Results: Expression of ARG2, IL4, RPL13 A, TGFBR3, and EGFR decreased, whereas expression of RUNX2 was increased in stenotic wounds compared with nonstenotic tissue. Based on the cell types present in the trachea and wound healing, this expression profile indicates a lack of M2 anti-inflammatory macrophages, absent epithelial cells, and transforming growth factor ß1-induced signaling. Conclusions: These findings represent a significant step for tracheal tissue engineering by identifying several key mechanisms present in stenotic granulation tissue. Further research must be conducted to determine what modifications of the graft substrate and which coadministered therapeutics can be used to prevent the development of hypertrophic granulation tissue.

Lobectomy Demonstrates Superior Survival Than Segmentectomy for High-Grade Non-Small Cell Lung Cancer: The National Cancer Database Analysis.

BACKGROUND: Current recommendations for segmentectomy for non-small cell lung cancer (NSCLC) include size ≤2 cm, margins ≥ 2 cm, and no nodal involvement. This study further stratifies the selection criteria for segmentectomy using the National Cancer Database (NCDB). METHODS: The NCDB was queried for patients with high-grade (poorly/undifferentiated) T1a/b peripheral NSCLC (tumor size ≤2 cm), who underwent either lobectomy or segmentectomy. Patients with pathologic node-positive disease or who received neoadjuvant/adjuvant treatments were excluded. Propensity score analysis was used to adjust for differences in pretreatment characteristics. RESULTS: 11 091 patients were included with 10 413 patients (93.9%) treated with lobectomy and 678 patients (6.1%) underwent segmentectomy. In a propensity matched pair analysis of 1282 patients, lobectomy showed significantly improved median survival of 88.48 months vs 68.30 months for segmentectomy, P = .004. On multivariate Cox regression, lobectomy was associated with significantly improved survival (hazard ratio (HR): .81, 95% CI .72-.92, P = .001). Subgroup analysis of propensity score matched patients with a Charlson-Deyo comorbidity score (CDCC) of 0 also demonstrated a trend of improved survival with lobectomy. DISCUSSION: Lobectomy may confer significant survival advantage over segmentectomy for high-grade NSCLC (≤2 cm). More work is needed to further stratify various NSCLC histologies with their respective grades allowing more comprehensive selection criteria for segmentectomy.

Increasing Time-to-Treatment for Lung Cancer: Are We Going Backward?

BACKGROUND: Treatment delays in lung cancer care in the United States may be attributable to a diverse range of patient, provider, and institutional factors, the precise contributions of which remain unclear. The objective of our study was to use the National Cancer Database to investigate specific predictors of increased time-to-treatment initiation. METHODS: We identified 567 783 patients undergoing treatment for stage I to stage IV non-small cell lung cancer during 2010 to 2018. Time-to-treatment initiation was defined as the number of days from radiologic diagnosis to initiation of first treatment. We used mixed effect negative binomial regression to determine predictors of time-to-treatment initiation. RESULTS: We noted a steady rise in the overall mean time-to-treatment initiation interval from 33 days (2010) to 39 days (2018; P < .01). Black race, a later year at diagnosis, nonprivate insurance, and diagnosis and treatment at different facilities were independent predictors of increased time-to-treatment initiation, irrespective of disease stage. Compared with White race, Black race corresponded to a 15% to 20% increase in time-to-treatment initiation, depending on disease stage (P < .01). For stages I and II, radiation as first course of therapy corresponded with a 69% and 33% increase in time-to-treatment initiation, respectively, compared with surgery (P < .01). CONCLUSIONS: Lung cancer treatment initiation times have seen an upward trajectory in recent years. Black patients encountered significantly longer treatment initiation times, regardless of treatment modality or disease stage. Prolonged initiation times appear to contribute to existing health care disparities by disproportionately affecting medically underserved communities.

The Scan, the Needle, or the Knife? National Trends in Diagnosing Stage I Lung Cancer.

OBJECTIVE: Indeterminate lung nodules have been increasingly discovered since the expansion of lung cancer screening programs. The diagnostic approach for suspicious nodules varies based on institutional resources and preferences. The aim of this study is to analyze factors associated with diagnostic modalities used for early-stage non-small cell lung cancer (NSCLC). METHODS: The National Cancer Database was queried for all patients with stage I NSCLC from 2004 to 2015. Four diagnostic modalities were identified, including clinical radiography alone (CRA), bronchial cytology (BC), procedural biopsy (PB), and surgical biopsy (SB). A multivariable multinomial logistic regression was used to assess associations of patient demographics, cancer characteristics, and facility characteristics with these modalities. RESULTS: Of 250,614 patients, 4,233 (1.7%) had CRA, 5,226 (2.1%) had BC, 147,621 (59.9%) had PB, and 93,534 (37.3%) had SB. Older patients were more likely to receive CRA (adjusted odds ratio [ORadj] = 5.3) and less likely to receive SB (ORadj = 0.73). Black patients were less likely to receive SB (ORadj = 0.83) and more likely to receive BC (ORadj = 1.31). Private insurance was associated with SB (ORadj = 1.11), whereas Medicaid was associated with BC (ORadj = 1.21). Patients more than 50 miles from the facility were more likely to undergo SB (ORadj = 1.25 vs PB; ORadj = 1.30 vs CRA; ORadj = 1.38 vs BC). Patients receiving SB had shorter days from diagnosis to treatment (23.0 vs 53.5 to 64.7 for other modalities, P < 0.001). CONCLUSIONS: Diagnostic SB to confirm early-stage NSCLC was associated with younger age, greater travel distance, and shorter time to treatment in comparison with other modalities. Black race and non-private insurance were less likely to be associated with SB.

Treatment quality and outcomes vary with hospital burden of uninsured and Medicaid patients with cancer in early non-small cell lung cancer.

Objectives: Safety-net hospitals deliver a significant level of care to uninsured patients, Medicaid-enrolled patients, and other vulnerable patients. Little is known about the impact of safety-net hospital status on outcomes in non-small cell lung cancer. We aimed to compare treatment characteristics and outcomes between hospitals categorized according to their relative burden of uninsured or Medicaid-enrolled patients with non-small cell lung cancer. Methods: We queried the National Cancer Database for patients with clinical stage I and II non-small cell lung cancer presenting from 2004 to 2018. We categorized hospitals on the basis of their relative burden of uninsured or Medicaid-enrolled patients with non-small cell lung cancer into low-burden (<8.2%), medium-burden (8.2%-12.0%), high-burden (12.1%-16.8%), and highest burden (>16.8%) quartiles. We investigated the impact of care at these hospitals on outcomes while controlling for sociodemographic, clinical, and facility characteristics. Results: We identified 204,189 patients treated at 1286 facilities. There were 592 low-burden, 297 medium-burden, 219 high-burden, and 178 highest burden hospitals. Patients at highest burden hospitals were more likely to be younger, male, Black, and Hispanic (P < .01), and to reside in rural, low-income, and low-educated regions (P < .01). Patients at these facilities had a greater likelihood of not receiving surgery, undergoing an open procedure, undergoing a regional lymph node examination involving less than 10 lymph nodes, having a length of stay more than 4 days, and not receiving treatment (P < .05). Conclusions: Our results indicate reduced treatment quality and higher mortality in patients undergoing surgery for early non-small cell lung cancer at hospitals with an increased burden of uninsured or Medicaid-enrolled patients with non-small cell lung cancer. There is a need to raise the standard of care to improve outcomes in vulnerable populations.

Robotic-assisted thoracoscopic surgery demonstrates a lower rate of conversion to thoracotomy than video-assisted thoracoscopic surgery for complex lobectomies.

OBJECTIVES: Locally advanced lung cancers present a significant challenge to minimally invasive thoracic surgeons. An increasing number of centres have adopted robotic-assisted thoracoscopic surgeries for these complex operations. In this study, we compare surgical margins achieved, conversion rates to thoracotomy, perioperative mortality and 30-day readmission rates for robotic and video-assisted thoracoscopic surgery (VATS) lobectomy for locally advanced lung cancers. METHODS: Using the National Cancer Database, we identified patients with non-small-cell lung cancer who received neoadjuvant chemotherapy/radiotherapy, had clinical N1/N2 disease or in the absence of these 2 features had a tumour >5 cm treated with either robotic or VATS lobectomy between 2010 and 2016. Perioperative outcomes and conversion rates were compared between robotic and VATS lobectomy. RESULTS: A total of 9512 patients met our inclusion criteria with 2123 (22.3%) treated with robotic lobectomy and 7389 (77.7%) treated with VATS lobectomy. Comparable R0 resections, 30- and 90-day mortality and 30-day readmission rates were observed for robotic and VATS lobectomy while a higher rate of conversion to thoracotomy was observed for VATS (aOR = 1.99, 95% confidence interval = 1.65, 2.39, P < 0.001). CONCLUSIONS: Our analysis of the National Cancer Database suggests that robotic lobectomy for complex lung resections achieves similar perioperative outcomes and R0 resections as VATS lobectomy with the exception of a lower rate of conversion to thoracotomy.

Conversion to Thoracotomy in Non-Small Cell Lung Cancer: Risk Factors and Perioperative Outcomes.

Objective: We aimed to identify predictors of conversion to thoracotomy and test the hypothesis that conversion is associated with inferior perioperative outcomes in non-small cell lung cancer (NSCLC). Methods: We queried the National Cancer Database for patients with stage I to III NSCLC undergoing minimally invasive surgery (MIS) during 2010 to 2016. We compared clinicopathologic factors between patients undergoing MIS with and without conversion. We fitted multivariable regression models to identify independent predictors of conversion and compare perioperative outcomes between the 2 groups. Results: A rising trend in the use of MIS was accompanied by a declining trend in the rate of conversion to thoracotomy. A total of 11.3% of the 83,219 cases were converted. Conversion was associated with a higher Charlson-Deyo score, squamous histology, nodal involvement, high tumor grade, tumor size ≥5 cm, and a higher T stage (P < 0.05). Successful MIS without conversion was predicted by advanced age, sublobar resection, robotic approach, and treatment at an academic high-volume facility (P < 0.05). Conversion was linked to longer hospital stays, higher 30-day and 90-day mortality, and unplanned readmission (P < 0.05), irrespective of the type of MIS approach. Conclusions: Conversion rates for video-assisted and robot-assisted thoracoscopic surgery have seen a decline in recent years. Irrespective of the type of MIS approach, conversion was associated with inferior perioperative outcomes. The robotic approach and treatment at an academic high-volume facility were associated with a lower likelihood of conversion. Early recognition of the individual risk factors for conversion may help to counsel patients about the likelihood of, and detriments associated with, conversion and ultimately reduce conversion rates.

Social determinants and facility type impact adherence to best practices in operable IIIAN2 lung cancer.

OBJECTIVES: We aimed to identify patient- and facility-specific predictors of collective adherence to 4 recommended best treatment practices in operable IIIAN2 non-small-cell lung cancer (NSCLC) and test the hypothesis that collective adherence is associated with superior survival. METHODS: We queried the National Cancer Database for clinical stage IIIAN2 NSCLC patients undergoing surgery during 2010-2015. The following best practices were examined: performance of an anatomic resection, performance of an R0 resection, examination of regional lymph nodes and administration of induction therapy. Multivariable regression models were fitted to identify independent predictors of guideline-concordance. RESULTS: We identified 7371 patients undergoing surgical resection for IIIAN2 lung cancer, of whom 90.8% underwent an anatomic resection, 88.2% received an R0 resection, 92.5% underwent a regional lymph node examination, 41.6% received induction therapy and 33.7% received all 4 best practices. Higher income, private insurance and treatment at an academic facility were independently associated with adherence to all 4 best practices (P < 0.01). A lower level of education and residence in a rural county were associated with a lack of adherence (P < 0.05). Adherence to all 4 practices correlated with improved survival (P < 0.01). CONCLUSIONS: National adherence to best treatment practices in operable IIIAN2 lung cancer was variable as evidenced by the majority of patients not receiving recommended induction therapy. Socioeconomic factors and facility type are important determinants of guideline-concordance. Future efforts to improve outcomes should take this into account since guideline concordance, in the form of collective adherence to all 4 best practices, was associated with improved survival.

Travelling to a High-Volume Center Confers Improved Survival in Stage I Non-small Cell Lung Cancer.

BACKGROUND: The association of hospital volume with outcomes has been assessed previously for patients with non-small cell lung cancer (NSCLC), but there are limited data on the cumulative effect of travel burden and hospital volume on treatment decisions and survival outcomes. We used the National Cancer Database to evaluate this relationship in early-stage NSCLC. METHODS: Outcomes of interest were compared between 2 propensity-matched groups with stage I NSCLC: patients in the bottom quartile of distance travelled who underwent surgery at low-volume centers (Local) and those in the top quartile of distance travelled who received surgery at high-volume centers (Distant). Outcomes included type of resection (anatomic or nonanatomic), time to resection (< or ≥8 weeks), number of lymph nodes examined (< or ≥10 nodes) and R0 resection. RESULTS: We identified 3325 Local patients who travelled 2.3 miles (interquartile range [IQR]: 1.4-3.3 miles) to centers that treated 10.5 (IQR: 6.5-16.5) stage I NSCLCs/year and 3361 Distant patients who travelled 40.0 miles (IQR: 29.1-63.4 miles) to centers treating 56.9 (IQR: 40.1-84.7) stage I NSCLCs/year. Local patients were less likely to receive surgery <8 weeks post-diagnosis, have ≥10 lymph nodes examined during surgery, and undergo an R0 resection (all P < .01). Distant patients had shorter hospital stays and superior median survival, both P < .01. CONCLUSIONS: Patients travelling longer distances to high-volume centers receive better and more timely surgical care, leading to shorter hospital stays and improved survival outcomes. Regionalization of lung cancer care by improving travel support to larger treatment facilities may help improve early-stage NSCLC outcomes.

Invasive thymoma - Which patients benefit from post-operative radiotherapy?

BACKGROUND: The aim of this study is to identify patients with thymoma who should receive post-operative radiotherapy. METHODS: The Surveillance, Epidemiology, and End Results database was queried for stage IIB-IV thymoma patients diagnosed during 1988-2015. We analyzed the prognostic implications of various clinical-pathological factors by comparing the outcomes of those who received surgery with and without post-operative radiotherapy. RESULTS: A total of 1120 patients were identified; 62% received post-operative radiotherapy and 38% underwent surgery alone. In a propensity-matched cohort of 812 patients, no survival difference was seen in World Health Organization A, AB, B1, B2, or B3 tumors with the addition of post-operative radiotherapy to surgery (p>0.05). Post-operative radiotherapy also did not improve survival over surgery alone for tumors ≥ or < less than the 4 cm, 7 cm, 10 cm, and 13 cm cutoffs, all p>0.05. Post-operative radiotherapy was an independent, positive prognostic indicator only in the subgroup with stage III disease and in those receiving chemotherapy in addition to post-operative radiotherapy, both p<0.05. CONCLUSIONS: Patients with stage III thymoma are most likely to benefit from the addition of post-operative radiotherapy to surgical treatments. Tumor size or World Health Organization histology alone should not be criteria for determining the need for post-operative radiotherapy in locally advanced thymoma. Masaoka-Koga stage, which has traditionally been used to help make such decisions, appears to be the most reliable determinant of the use of post-operative radiotherapy.

Novel composite trachea grafts using 3-dimensional printing.

Objective: Porcine-derived small intestine submucosa (SIS) extracellular matrix (ECM) surgical patches claim to have greater regenerative properties compared with dermal extracellular matrices. We hypothesized that using SIS-ECM in a bioengineered composite tracheal graft would allow better incorporation into the native tissue. Methods: Two types of size-matched polycaprolactone support scaffolds were designed: rigid and flexible. The SIS-ECM was wrapped around the polycaprolactone supports lining the inside and outside of the graft. The grafts were implanted in 4 Yorkshire pigs, replacing an ∼2 cm segment of native trachea. Airway patency was evaluated with computed tomography scans and explanted grafts were examined grossly and histologically. Results: All animals survived through the immediate postoperative period. Generally, extraluminal examination showed a smooth transition between native and graft without significant volumetric loss. Animals that received the flexible design survived ∼10 days longer than those that received the rigid design; however, severe perianastomotic intraluminal granulation tissue was observed. The rigid design had less significant intraluminal granulation tissue development at the distal anastomosis, but partial dehiscence had occurred at the proximal anastomosis interrupting graft incorporation. Conclusions: The generally good extraluminal graft incorporation in our composite tracheal graft highlights some increased regenerative capabilities of SIS-ECM. However, the presence of intraluminal granulation tissue indicates that its use as an off-the-shelf, unaltered substrate in an airway graft is still not ideal. Further research must be conducted to determine whether a modification of the substrate is possible to enhance luminal airway incorporation and to exert control over the mechanisms responsible for granulation tissue development.

Anatomic resection has superior long-term survival compared with wedge resection for second primary lung cancer after prior lobectomy.

OBJECTIVES: The extent of surgical resection for early-stage second primary lung cancer (SPLC) in patients with a previous lobectomy is unclear. We sought to compare anatomic lung resections (lobectomy and segmentectomy) and wedge resections for small peripheral SPLC using a population-based database. METHODS: The Surveillance, Epidemiology and End Results database was queried for all patients with ≤2 cm peripheral SPLC diagnosed between 2004 and 2015 who underwent prior lobectomy for the first primary and surgical resection only for the SPLC. American College of Chest Physicians guidelines were used to classify SPLC. Kaplan-Meier analysis and multivariable Cox regression were used to compare overall survival. RESULTS: A total of 356 patients met the inclusion criteria with 203 (57%) treated with wedge resection and 153 (43%) treated with anatomic resection. Significantly better median survival was observed with anatomic resection than with wedge resection using a Kaplan-Meier analysis (124 vs 63 months; P < 0.001). With multivariable Cox regression, improved long-term survival was observed for anatomic resection (hazard ratio: 0.44, confidence interval: 0.27-0.70; P = 0.001). Improvement in survival was demonstrated with wedge resection when lymph node sampling was done. Lastly, we calculated the average treatment effect on the treated with inverse probability weighting for a subgroup of patients and found that those with wedge resection and lymph node sampling had shorter long-term survival times. CONCLUSIONS: Anatomic resections may provide better long-term survival than wedge resections for patients with early-stage peripheral SPLC after prior lobectomy. Significant improvement in survival was observed with wedge resection for SPLC when adequate lymph node dissection was performed.