Background Two recent randomized clinical trials have shown sublobar resection to be noninferior to lobectomy in node-negative non-small cell lung cancer ≤2 cm. As a result, the use of sublobar resection in early lung cancer patients has significantly increased. Consensus recommendations are needed to guide its appropriate use. Methods The Society of Thoracic Surgeons Workforce on Evidence-Based Surgery assembled a panel of thoracic surgeons with clinical and methodological expertise to review the existing literature on this topic. A modified Delphi method, with boundaries and thresholds determined a priori, was used until 75% agreement on the statements was reached. Results The panel identified 7 key areas of controversy. Three rounds of voting were required to reach >75% agreement on 21 statements to help guide appropriate use of sublobar resection in early-stage lung cancer. Conclusions Despite results of recent randomized clinical trials, several key questions remain regarding sublobar resection for early-stage non-small cell lung cancer. These statements will provide further guidance for clinicians considering the different surgical options.

BACKGROUND:Few germline susceptibility genes have been well established for lung cancer. We aimed to evaluate associations between germline variants in known hereditary cancer genes and lung cancer risk. METHODS:We analyzed subjects of European ancestry from two datasets: 2,272 LC cases and 185,510 controls from the UK Biobank, and 824 LC cases from Rush University Medical Center (RUSH) with 56,878 population controls from the Genome Aggregation Database (gnomAD). Rare pathogenic germline variants in 123 ClinGen-curated hereditary cancer genes were first tested for lung cancer risk in the UK Biobank using gene-based burden testing (robust SKAT-O). Genes with suggestive associations were further evaluated in the RUSH/gnomAD dataset. Meta-analysis of the two datasets was performed to estimate overall evidence and pooled odds ratios. RESULTS:Rare germline variants in ten genes showed nominally significant associations with lung cancer in the UK Biobank (p<0.05), and TP53 showed a borderline signal (p=0.11). These genes were tested in the RUSH/gnomAD dataset, and meta-analysis identified suggestive evidence supporting eight genes associated with increased lung cancer risk (p<0.05), including three previously reported lung cancer genes (ATM, BRCA2, TP53) and five novel genes (RB1, MET, CYLD, PDGFRA, CTNNA1). In the UK Biobank incident lung cancer cohort, aggregated rare pathogenic variants in these eight genes were significantly associated with lung cancer risk and earlier age at lung cancer diagnosis, independent and complementary to smoking history at recruitment. CONCLUSIONS:Suggestive evidence supporting associations between rare germline variants in eight hereditary cancer genes and lung cancer were obtained from two large independent datasets.

With the publication of CALGB 140503, an increase in wedge resections for small, peripheral non-small cell lung cancer is expected; however, a relative paucity of data exists as to what defines a high quality oncologic wedge resection. The Thoracic Surgery Outcomes Research Network (ThORN), through expert discussion, guided by review of what limited data does exist, and through use of a modified Delphi process, provides these consensus statements defining an oncologically sound, high quality wedge resection. The statements are classified into five categories: 1) Preoperative Considerations 2) Technical Aspects 3) Lymph Node Assessment 4) Margin Assessment and 5) Tissue Handling by Pathology.

Supplementary Figures 1-2 from Three-Dimensional Collagen I Promotes Gemcitabine Resistance in Pancreatic Cancer through MT1-MMP–Mediated Expression of HMGA2

Supplementary Data from Crosstalk between Mast Cells and Pancreatic Cancer Cells Contributes to Pancreatic Tumor Progression

Supplementary Figure 3 from Three-Dimensional Collagen I Promotes Gemcitabine Resistance in Pancreatic Cancer through MT1-MMP–Mediated Expression of HMGA2

Published studies on association of germline monogenic genes and lung cancer risk were inconsistent. We systematically reviewed published papers, identified statistically significant genes and performed a confirmation study in 2,050 lung cancer cases and 198,553 controls. We confirmed 3 lung cancer risk-associated genes ( ATM, BRCA2 , and TP53 ). These results offer a tool for identifying high-risk subjects of lung cancer. Introduction/Background: Published studies on association of germline monogenic genes and lung cancer risk were inconsistent. Our objective is to assess the validity of reported candidate monogenic genes for their association with lung cancer. Materials and Methods: A systematic review of published papers prior to August 2022 was performed first to identify all genes where germline mutations were associated with lung cancer risk. We then performed a confirmation study in 2,050 lung cancer cases and 198,553 controls in the UK Biobank (UKB). Germline mutations of these genes were identified from sequencing data and annotated using The American College of Medical Genetics cr iter ia. The robust SKAT-O, a gene-based analysis that properly controls for false positives due to unbalanced case-control ratio, was used for association tests adjusting for age at recruitment, gender, and genetic background. Results: The systematic review identified 12 genes that were statistically significantly associated with lung cancer risk in at least one study ( P When pathogenic/likely pathogenic mutations were aggregated within each gene, the association was confirmed for ATM ( P = 4.47E-4) at the study-wise significance level ( P < .0042, Bonferroni correction for 12 tests). Suggestive evidence of association was found for 2 other genes, BRCA2 ( P = .007) and TP53 ( P = .03). Among these 3 genes, the lung cancer risks range from 1.95 ( BRCA2 ) to 5.28 ( TP53 ). Conclusion: This study provides statistical evidence for association of previously reported genes and lung cancer risk and has clinical utility for risk assessment and genetic counseling.

Supplementary Figure 1 from Mast Cell 5-Lipoxygenase Activity Promotes Intestinal Polyposis in APCΔ468 Mice

We present a case of an advanced squamous cell carcinoma encroaching on a patient's left internal mammary artery bypass graft. Tumor board consensus was to proceed with 2 cycles of neoadjuvant chemotherapy followed by resection. Intraoperatively, the left internal mammary artery bypass could not be safely dissected from the adjacent pleura, but frozen sections were negative for malignant transformation. Final pathologic examination showed a complete pathologic response to neoadjuvant chemotherapy, and surveillance imaging is now negative for recurrence 5 years postoperatively. Although malignant neoplasms invading into adjacent vasculature can post technical challenges during an operation, neoadjuvant therapy can downstage these tumors and make resection feasible without added morbidity.

Pill-induced esophagitis due to calcium supplements is extremely uncommon. We present a 60-year-old female patient with pill-induced esophageal perforation complicated by mediastinal abscess and esophago-pleural fistula following ingestion of a single over-the-counter "bone supplement" tablet containing mainly calcium.

Background: Real-world treatment practices for positive mediastinal nodal disease in non-small cell lung cancer (NSCLC) continues to vary despite guidelines. We aim to assess national trends in the treatment of pathologic-N2 disease, and evaluate the association with clinical nodal staging and timing of systemic therapy. Methods: The National Cancer Database was queried for patients with NSCLC who underwent lobectomy and had pathologic-N2 disease from 2010-2017. NCCN guideline concordance was evaluated. cN2 patients were analyzed based on timing of systemic therapy and response. Multivariable logistic regression evaluated outcomes by type of systemic therapy. Survival analysis utilized Cox proportional hazards regression and Kaplan-Meter method Results: 10,225 patients met inclusion criteria. 54% of patients were understaged prior to surgery as either cN0 or cN1. Of clinically staged N2 patients, 56% received NCCN recommended neoadjuvant therapy. Annual guideline concordance increased until 2016 to a max of 62.9%. Neoadjuvant and adjuvant systemic therapy showed an overall survival benefit compared with no systemic therapy (HR 0.54 & 0.57), but no difference when compared against each other. Complete response after neoadjuvant therapy was associated with improved survival (5-year OS 56.1%, P<0.001), while partial response, no-response, and adjuvant therapy were similar. All systemic treatment strategies improved survival compared with no systemic therapy (5-year OS 24.5%). Conclusions: Guideline concordance for treatment of cN2 disease has been increasing, but still not followed in over 1/3 of patients. Responsiveness to neoadjuvant therapy appears to be a predictor of survival, and may become a prognostic adjunct for determining which patients would benefit from additional systemic therapy.

Objective:To determine the frequency of pathogenic mutations in high-penetrance genes (HPGs) in patients with non-small cell lung cancer (NSCLC) and identify whether such mutations are associated with clinicopathologic outcomes. Methods:Patients with NSCLC who had consented to participate in a linked clinical database and biorepository underwent germline DNA sequencing using a next-generation sequencing panel that included cancer-associated HPGs and cancer risk-associated single nucleotide polymorphisms (SNPs). These data were linked to the clinical database to assess for associations between germline variants and clinical phenotype using Fisher's exact test and multivariable logistic and Cox regression. Results:We analyzed 151 patients, among whom 33% carried any pathogenic HPG mutation and 23% had a genetic risk score (GRS) >1.5. Among the patients without any pathogenic mutation, 31% were at cancer stage II or higher, compared with 55% of those with 2 types of HPG mutations (P = .0293); 40% of patients with both types of HPG mutations had cancer recurrence, compared with 21% of patients without both types (P = .0644). In multivariable analysis, the presence of 2 types of HPG mutations was associated with higher cancer stage (odds ratio [OR], 3.32; P = .0228), increased recurrence of primary tumor (OR, 2.93; P = .0527), shorter time to recurrence (hazard ratio [HR], 3.03; P = .0119), and decreased cancer-specific (HR, 3.53; P = .0039) and overall survival (HR, 2.44; P = .0114). Conclusions:The presence of mutations in HPGs is associated with higher cancer stage, increased risk of recurrence, and worse cancer-specific and overall survival in patients with NSCLC. Further large studies are needed to better delineate the role of HPGs in cancer recurrence and the potential benefit of adjuvant treatment in patients harboring such mutations.

Chronic obstructive pulmonary disease is a challenging disease to treat, and at advanced stages of the disease, procedural interventions become some of the only effective methods for improving quality of life. However, these procedures are often very costly. This article reviews the medical literature on cost-effectiveness of lung volume reduction surgery and bronchoscopic valve placement for lung volume reduction. It discusses the anticipated costs and economic impact in the future as technique is perfected and outcomes are improved.

Central MessageAutomated segmentation of standard computed tomography scans, coupled with an immersive VR environment is technically feasible and may improve our ability to perform complex segmental resections.See Article page 309. Automated segmentation of standard computed tomography scans, coupled with an immersive VR environment is technically feasible and may improve our ability to perform complex segmental resections. See Article page 309. The past decade has brought a significant increase in the performance of pulmonary segmentectomies, including "complex" segmentectomies that involve the division of multiple intersegmental planes.1Servais E.L. Towe C.W. Brown L.M. Broderick S.R. Block M.I. Burfeind W.R. et al.The Society of Thoracic Surgeons General Thoracic Surgery database: 2020 update on outcomes and research.Ann Thorac Surg. 2020; 110: 768-775Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 2Handa Y. Tsutani Y. Mimae T. Miyata Y. Imai K. Ito H. et al.Oncologic outcomes of complex segmentectomy: a multicenter propensity score-matched analysis.Ann Thorac Surg. 2021; 111: 1044-1051Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 3Handa Y. Tsutani Y. Mimae T. Miyata Y. Okada M. Complex segmentectomy in the treatment of stage IA non–small-cell lung cancer.Eur J Cardiothorac Surg. 2020; 57: 114-121Crossref PubMed Scopus (27) Google Scholar, 4Suzuki K. Saji H. Aokage K. Watanabe S.I. Okada M. Mizusawa J. et al.Comparison of pulmonary segmentectomy and lobectomy: safety results of a randomized trial.J Thorac Cardiovasc Surg. 2019; 158: 895-907Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar With increasing use of lung cancer screening, this trend is not likely to abate. Successful completion of these operations can be challenging owing not only to their technical complexity but also to the difficulty in accurately identifying the correct anatomic segment on standard preoperative imaging. In their very interesting article in this issue of JTCVS Techniques, Sadeghi and colleagues5Sadeghi A.H. Maat A.P.W.M. Taverne Y.J.H.J. Cornelissen R. Dingemans A.-M.C. Bogers A.J.J.C. et al.Virtual reality and artificial intelligence for 3-dimensional planning of lung segmentectomies.J Thorac Cardiovasc Surg Tech. 2021; 7: 309-321Scopus (3) Google Scholar describe a novel technique to aid the preoperative planning of these procedures. They have developed a virtual reality (VR)-based tool that uses artificial intelligence to create fully segmented and colorized reconstructions of preoperative computed tomography scans. The use of artificial intelligence allows significant portions of the overall process to be automated, with a final product that can then be manipulated and studied by the surgeon in an immersive VR environment. In this pilot study of 10 patients, the authors focused primarily on technical feasibility and preoperative workflow, along with some preliminary clinical data on the accuracy and impact of the software. They were able to achieve complete segmental maps inclusive of the arteries, veins, and bronchi and were able to manipulate these maps within the VR platform in all 10 patients. After VR evaluation of the 3-dimensional segmental models, the surgical plan was changed in 4 of 10 patients. Intraoperative anatomy corresponded to the VR images in 100% of the patients, though this was based on postprocedural surveys of the operating surgeon and not on any independent assessment. Both surgeons who used the system gave it high ratings for ease of use, overall usefulness, and likelihood of future use. Interestingly, both surgeons saw this as a supplement to conventional methods, not a replacement. Clinical outcomes were limited, but an R0 resection was achieved in all patients. This very exciting study of a promising new technology is not without limitations. It is clearly a pilot study and lacks controls for interrater reliability, does not have a comparison with more standard 3-dimensional reconstruction techniques without segmentation and VR manipulation (or for that matter, with standard imaging techniques), and does not provide any true measure of how this tool impacts clinical outcomes. Future studies will need to compare patients who had more standard evaluation and VR-based segmental evaluation along with providing outcomes such as margin positivity, margin size, total lung segments removed, operative time, air leak, and others. Furthermore, a true blinded assessment of the VR accuracy is also not included in this early work. As utilization of lung cancer screening expands, we will increasingly see small, subcentimeter tumors and a concomitant increase in segmental resection. Such resections will be further facilitated by future technological innovations, including VR simulation, enhanced robotics, augmented reality, and molecular enhanced imaging. Although there remains much work to do, the authors should be commended for helping push our field forward in pursuit of better outcomes for our patients. Virtual reality and artificial intelligence for 3-dimensional planning of lung segmentectomiesJTCVS TechniquesVol. 7PreviewThere has been an increasing trend toward pulmonary segmentectomies to treat early-stage lung cancer, small intrapulmonary metastases, and localized benign pathology. A complete preoperative understanding of pulmonary anatomy is essential for accurate surgical planning and case selection. Identifying intersegmental divisions is extremely difficult when performed on computed tomography. For the preoperative planning of segmentectomies, virtual reality (VR) and artificial intelligence could allow 3-dimensional visualization of the complex anatomy of pulmonary segmental divisions, vascular arborization, and bronchial anatomy. Full-Text PDF Open Access

6080 Background: Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV) types 6 & 11. RRP proliferates in the respiratory tract impacting breathing, swallowing, and voice and carries a 1-4% risk of malignant transformation.There is no curative therapy for RRP. Given the tolerized host immune response against HPV, the safety and efficacy of pembrolizumab (pembro) as an alternative treatment for this patient population was evaluated in a phase II clinical trial. Patient reported outcomes (PROs) were assessed during the trial to capture the patient perspective of pembro as an alternative to surgery or in office procedures, both standard of care (SOC). Methods: RRP patients who had previously undergone >3 procedures in any year, or with known tracheal or pulmonary involvement prior to study entry were treated with pembro 200mg every 3 weeks. The primary endpoint of the trial was best ‘overall response rate’ (ORR) measured by an endoscopic-based disease burden score (lower score reflects better ‘response’) and/or RECIST 1.1, secondary endpoint included PROs. Twenty-one patients were required to assess the primary endpoint. Most of the QoL surveys used Likert scale to assess PROs (‘never, sometimes, often, most of the time, always’). The percentage reporting ’never’ having an issue with symptom or activity at baseline, 6 months, and at time of ORR (nadir disease burden score) is reported here. Results: Twenty-one patients were accrued. Median age (range) was 45 (19-68), 57% (12/21) were male and 67% (14/21) were white. Questionnaire completion rates were 100% at baseline, 90% at 6 months, and 85% at ORR. Improvement in: social interactions (less difficulty with: physical intimacy [38%,56%,65% reporting ‘never’ at baseline, 6 months, and at ORR respectively]), discussing disease diagnosis [19%,21%,39%]); personal feelings (less depression [14%,32%,33%], less anxiety [5%,16%,22%], less embarrassment [19%,37%,50%]), and work-related absences (less frequently fabricating reasons for work absence due to disease-related treatment [57%,78%,56%] and less utilization of family vacation or FMLA for disease treatment [29%,53%,56%]) were reported. At ORR, 72% (13/18) patients reported that IV infusion was not emotionally burdensome and 78% (14/18) reported it as the preferred treatment relative to their perceived experience with SOC surgery or in office procedures. Conclusions: PRO results show consistent benefit in key aspects of the patient experience with pembro over procedure based SOC further supporting its overall clinical benefit in patients with HPV-associated RRP. Clinical trial information: NCT02632344.

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

The extraordinary demands of managing the COVID-19 pandemic has disrupted the world's ability to care for patients with thoracic malignancies. As a hospital's COVID-19 population increases and hospital resources are depleted, the ability to provide surgical care is progressively restricted, forcing surgeons to prioritize among their cancer populations. Representatives from multiple cancer, surgical, and research organizations have come together to provide a guide for triaging patients with thoracic malignancies as the impact of COVID-19 evolves as each hospital.