Effect of nutrient metabolism on cartilaginous tissue formation.

A major shortcoming in cartilage tissue engineering is the low biosynthetic response of chondrocytes. While different strategies have been investigated, a novel approach may be to control nutrient metabolism. Although known for their anaerobic metabolism, chondrocytes are more synthetically active under conditions that elicit mixed aerobic-anaerobic metabolism. Here, we postulate this metabolic switch induces HIF-1α signaling resulting in improved growth. Transition to different metabolic states can result in the pooling of metabolites, several of which can stabilize HIF-1α by interfering with PHD2. Chondrocytes cultured under increased media availability accelerated tissue deposition with the greatest effect occurring at 2 ml/106 cells. Under higher media availability, metabolism switched from anaerobic to mixed aerobic-anaerobic. Around this transition, maximal changes in PHD2 activity, HIF-1α expression, and HIF-1 target gene expression were observed. Loss-of-function studies using YC-1 confirmed the involvement of HIF-1. Lastly, targeted metabolomic studies revealed that intracellular lactate and succinate correlated with PHD2 activity. This study demonstrates that cartilaginous tissue formation can be regulated by nutrient metabolism and that this response is mediated through changes in HIF-1α signaling. By harnessing this newly identified metabolic switch, engineered cartilage implants may be developed without the need for sophisticated methods which could aid translation to the clinic.

Surgical Advances in the Management of the Silent Sinus Syndrome: Our Experience and Review of the Literature.

Silent sinus syndrome is a rare disorder characterized by ipsilateral enophthalmos and hypoglobus caused by collapse of the orbital floor in the presence of asymptomatic long-term maxillary sinusitis. The basic principles in the management are to address the diseased sinus and reconstruct the orbit concurrently or separately. Failure to accurately restore the orbit volume can have significant consequences on the patient. In this article, we provide an update on current practices and highlight our experience of using computer-assisted planning and patient-specific implant in managing this syndrome.

Interaction of carbohydrate-binding modules with poly(ethylene terephthalate).

Poly(ethylene terephthalate) (PET) is one of the most widely applied synthetic polymers, but its hydrophobicity is challenging for many industrial applications. Biotechnological modification of PET surface can be achieved by PET hydrolyzing cutinases. In order to increase the adsorption towards their unnatural substrate, the enzymes are fused to carbohydrate-binding modules (CBMs) leading to enhanced activity. In this study, we identified novel PET binding CBMs and characterized the CBM-PET interplay. We developed a semi-quantitative method to detect CBMs bound to PET films. Screening of eight CBMs from diverse families for PET binding revealed one CBM that possesses a high affinity towards PET. Molecular dynamics (MD) simulations of the CBM-PET interface revealed tryptophan residues forming an aromatic triad on the peptide surface. Their interaction with phenyl rings of PET is stabilized by additional hydrogen bonds formed between amino acids close to the aromatic triad. Furthermore, the ratio of hydrophobic to polar contacts at the interface was identified as an important feature determining the strength of PET binding of CBMs. The interaction of CBM tryptophan residues with PET was confirmed experimentally by tryptophan quenching measurements after addition of PET nanoparticles to CBM. Our findings are useful for engineering PET hydrolyzing enzymes and may also find applications in functionalization of PET.

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.

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.

Passaged Articular Chondrocytes From the Superficial Zone and Deep Zone Can Regain Zone-Specific Properties After Redifferentiation.

BACKGROUND: Bioengineered cartilage is a developing therapeutic to repair cartilage defects. The matrix must be rich in collagen type II and aggrecan and mechanically competent, withstanding compressive and shearing loads. Biomechanical properties in native articular cartilage depend on the zonal architecture consisting of 3 zones: superficial, middle, and deep. The superficial zone chondrocytes produce lubricating proteoglycan-4, whereas the deep zone chondrocytes produce collagen type X, which allows for integration into the subchondral bone. Zonal and chondrogenic expression is lost after cell number expansion. Current cell-based therapies have limited capacity to regenerate the zonal structure of native cartilage. HYPOTHESIS: Both passaged superficial and deep zone chondrocytes at high density can form bioengineered cartilage that is rich in collagen type II and aggrecan; however, only passaged superficial zone-derived chondrocytes will express superficial zone-specific proteoglycan-4, and only passaged deep zone-derived chondrocytes will express deep zone-specific collagen type X. STUDY DESIGN: Controlled laboratory study. METHODS: Superficial and deep zone chondrocytes were isolated from bovine joints, and zonal subpopulations were separately expanded in 2-dimensional culture. At passage 2, superficial and deep zone chondrocytes were seeded, separately, in scaffold-free 3-dimensional culture within agarose wells and cultured in redifferentiation media. RESULTS: Monolayer expansion resulted in loss of expression for proteoglycan-4 and collagen type X in passaged superficial and deep zone chondrocytes, respectively. By passage 2, superficial and deep zone chondrocytes had similar expression for dedifferentiated molecules collagen type I and tenascin C. Redifferentiation of both superficial and deep zone chondrocytes led to the expression of collagen type II and aggrecan in both passaged chondrocyte populations. However, only redifferentiated deep zone chondrocytes expressed collagen type X, and only redifferentiated superficial zone chondrocytes expressed and secreted proteoglycan-4. Additionally, redifferentiated deep zone chondrocytes produced a thicker and more robust tissue compared with superficial zone chondrocytes. CONCLUSION: The recapitulation of the primary phenotype from passaged zonal chondrocytes introduces a novel method of functional bioengineering of cartilage that resembles the zone-specific biological properties of native cartilage. CLINICAL RELEVANCE: The recapitulation of the primary phenotype in zonal chondrocytes could be a possible method to tailor bioengineered cartilage to have zone-specific expression.

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.

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.

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.

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.

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.

Patient-specific 3-dimensional lung modelling: next-generation imaging helps guide precise surgical resection.

Recent strides have allowed the consolidation of routine imaging modalities with highly accurate reconstruction software to aid the operating surgeon generate patient-specific three-dimensional models. In this preliminary report, we describe our initial experience using a patient-specific reconstruction software to guide surgical resection for 2 patients with non-small-cell lung cancer. Digital imaging and communications in medicine data from patient chest CT scans was configured into IQQA BodyImaging Lung software to generate highly accurate maps of airways, vessels and segments as well as estimates of lung volumes. Models generated aided us in planning appropriate lung cancer resection procedures.

Successes and Failures in Tracheal Bioengineering: Lessons Learned.

BACKGROUND: Controversy in tracheal reconstruction using grafts and bioengineered constructs highlights the importance of animal studies before human application. Small animal models help to refine designs but do not adequately model sizes relevant to human anatomy. We have conducted extensive large animal studies and summarize our findings in 26 consecutive transplants. METHODS: We pooled 26 large animal studies together to investigate common elements related to successes and failures. In general the engineered tracheal graft consisted of a decellularized extracellular matrix surgical patch supported by a 3-dimensional-printed plastic polymer scaffold. Circumferential graft coverage ranged from 50% to 100%, spanning the length of 4 to 6 tracheal rings. Some grafts included embedded stem cells. Control grafts were fabricated without the support scaffold. At death grafts were harvested and examined grossly and through histology. RESULTS: The support scaffold prevented graft malacia and collapse. Luminal epithelialization was most extensive in grafts with smaller circumferential coverage. Smaller circumferential coverage was also associated with longest animal survival. Chondrogenesis was only observed in grafts with embedded stem cells. Survival time was shortest in 100% circumferential grafts. Granulation tissue was an issue for all graft designs. CONCLUSIONS: Large animal models capture challenges and complexities relevant to human anatomy. Development of granulation tissue remains a challenge, especially in circumferential grafts. Significant additional research is needed to investigate granulation tissue formation and to provide actionable insight into its management.

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.

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.

Lobectomy is superior to segmentectomy for peripheral high grade non-small cell lung cancer ≤2 cm.

BACKGROUND: Current practice guidelines recommend the following criteria for segmentectomy for non-small cell lung cancer (NSCLC): size ≤2 cm, margins ≥2 cm and no lymph node involvement. We sought to further stratify the selection criteria for segmentectomy for small peripheral high-grade tumors. METHODS: This retrospective database study was conducted using the Surveillance, Epidemiology and End Results (SEER) database. We queried for patients with high-grade (poorly differentiated/undifferentiated) pathological (p)T1a/b peripheral NSCLC (tumor size ≤2 cm), who underwent either lobectomy or segmentectomy between 2004 and 2015. Patients with node-positive disease or those who received any form of induction or adjuvant treatments were excluded. RESULTS: A total of 4,332 patients met the inclusion criteria, with 3,977 patients (91.8%) treated with lobectomy and 355 patients (8.2%) who underwent segmentectomy. In a propensity matched pair analysis of 640 patients, lobectomy (n=320) showed significantly improved 5-year survival of 45.9% vs. 33.8% for segmentectomy (n=320), P<0.01. In a multivariate Cox regression analysis, lobectomy was associated with significantly improved survival (HR: 0.84, 95% CI: 0.714-0.989, P=0.036). Interestingly, married status, adenocarcinoma histology, number of lymph nodes sampled were associated with better survival (P<0.05), while advanced age and male gender had worse survival outcomes (P<0.05). CONCLUSIONS: For small peripheral NSCLC ≤2 cm and high grades of tumor differentiation, lobectomy is associated with better long-term survival outcomes as compared to segmentectomy. Additional data is needed to further stratify various NSCLC histologies with their respective grades to allow for better selection for segmentectomy.