Longitudinal Follow-up of Medicare Patients after Esophageal Cancer Resection in the STS Database.

BACKGROUND: Understanding characteristics associated with survival following esophagectomy for cancer is critical to preoperative risk stratification. This study sought to define predictors for long-term survival following esophagectomy for cancer in Medicare patients. METHODS: The STS GTSD was queried for patients age>65 who underwent esophagectomy for cancer between 2012-2020 and linked to CMS data using a deterministic matching algorithm. Patient, hospital, and treatment variables were assessed using a multivariable Cox proportional hazards model to evaluate characteristics associated with long-term mortality and readmission. Kaplan-Meier and cumulative incidence curves were generated and differences evaluated using the Log-rank test and Gray's test respectively. RESULTS: After CMS linkage, 4,798 patients were included. 30-day and 90-day mortality in the study group was 3.84% and 7.45%, respectively. In the multivariable model, ASA>3, BMI>35, and diabetes were associated with increased mortality <90 days post-surgery, while pN/pT upstaging was associated with increased mortality >90 days post-surgery. Patients upstaged to pN(+) had a 147% increased mortality risk (aHR 2.47;95%CI2.02-3.02) and those that remained pN(+) a 75% increased mortality risk (aHR 1.75;95%CI1.57-1.95) compared to down-staged patients. Patients who were pT upstaged had a 109% (aHR 2.09;95%CI1.73-2.53) increased mortality risk compared to pT downstaged patients. Risk for readmission was independent of procedure type or approach and was higher in cStage>2, ASA>4, and pN+. CONCLUSIONS: Medicare patients undergoing esophagectomy for cancer have identifiable patient-specific predictors for short-term mortality and tumor-specific predictors for long-term mortality and readmission. In the absence of pathologic T and N downstaging, risk for long-term mortality and readmission are increased.

Minimally Invasive Pneumonectomy vs Open Pneumonectomy: Outcomes and Predictors of Conversion.

BACKGROUND: In the modern era, it is unknown if minimally invasive pneumonectomy for non-small cell lung cancer (NSCLC) provides a survival advantage over open pneumonectomy. METHODS: Patients who underwent pneumonectomy for NSCLC between 2015 and 2020 were queried from the National Cancer Database. Surgical approach was categorized as robot-assisted (RATS), video-assisted thoracoscopic (VATS), or open pneumonectomy on an intention-to-treat basis. Propensity score matching was performed to balance patient cohorts. Univariate and multivariate regression analyses were used to examine the association between surgical approach and 30 and 90-day mortality, and a Cox proportional hazards model was used to assess overall survival. RESULTS: Overall, 3784 patients were identified, including 73% open (n=2776), 19% VATS (n=725), and 8% RATS (n=283). The overall conversion rate from minimally invasive to open was 29.5% (n=298). After propensity matching 212 patients per cohort, there were no differences between open, VATS, and RATS 30-day (9.4% vs 8.5% vs 7.5%, p=0.807, respectively) or 90-day mortality (14.2% vs 12.3% vs 10.4%, p=0.516, respectively). Median overall survival was similar among open (48 months, 95% CI 35.6-64.1), VATS (51.0 months, 95% CI 34.9-72.3), and RATS approaches (50 months, 95% CI 42.6-NA, p=0.560). On multivariate analysis of the matched cohort, there was no association between approach and overall survival. RATS (OR 0.67, 95% CI 0.47-0.94, p=0.020) and neoadjuvant chemotherapy (OR 0.52, 95% CI 0.27-0.98, p=0.045) were found to be protective against conversion to open. CONCLUSIONS: Minimally-invasive pneumonectomy can be performed with short-term and long-term survival that are equivalent to open pneumonectomy.

Examination of Firefighting as an Occupational Exposure Criteria for Lung Cancer Screening.

PURPOSE: Firefighting is known to be carcinogenic to humans. However, current lung cancer screening guidelines do not account for occupational exposure. We hypothesize that firefighting is an independent risk factor associated with the development of high-risk lung nodules on low-dose CT (LDCT). METHODS: Members of a firefighter's union underwent LDCT at a single institution between April 2022 and June 2023 within a lung cancer screening program. Results were interpreted by designated chest radiologists and reported using the Lung-RADS scoring system. Demographic and radiographic data were recorded, and summary statistics are reported. RESULTS: 1347 individuals underwent lung cancer screening, with a median age of 51 years (IQR 42-58), including 56 (4.2%) females. Overall, 899 (66.7%) were never smokers, 345 (25.6%) were former smokers, and 103 (7.7%) were current smokers. There were 41 firefighters (3.0%) who had high-risk (Lung-RADS 3 or 4) nodules requiring intervention or surveillance, of which 21 (1.5%) were Lung-RADS 3 and 20 (1.5%) that were Lung-RADS 4. Of the firefighters with high-risk nodules, only 6 (14.6%) were eligible for LDCT based on current screening guidelines. There were 7 high-risk nodules (0.5%) that required procedural intervention, 6 (85.7%) of which were from the non-screening eligible cohort. There were also 20 never-smoking firefighters (57.1%) with high-risk nodules that were non-screening eligible. CONCLUSION: Firefighting, even in the absence of smoking history, may be associated with the development of high-risk lung nodules on LDCT. Carefully selected occupational exposures should be considered in the development of future lung cancer screening guidelines.

Women are Underrepresented in Non-small Cell Lung Cancer Clinical Trials: A Systematic Review.

PURPOSE: To perform a systematic review of clinical trials examining non-small cell lung cancer (NSCLC) to better understand the equity afforded to women in the study of lung cancer. METHODS: An electronic search was conducted for all NSCLC clinical trials published between 2010 and 2020 with included words "carcinoma, non-small cell, lung" and "non-small cell lung cancer." Studies from PubMed, Cochrane, and SCOPUS were included and were uploaded into Covidence to assist with systematic review. All articles were screened by two separate individuals and reviewed for location, study type, cancer stage, field of study of the research team, and percentage of females included. Student's t-test was used to compare the means of males and females. RESULTS: Across the 269 studies that met inclusion criteria, fewer females than males were enrolled (38.7% vs. 61.1%; p < 0.0001). Compared with studies from 2010 to 2015, those from 2016 to 2020 had greater representation of females (36.7% vs. 41.4%, p = 0.0091, respectively). Both nonsurgical and surgical studies enrolled fewer female than male patients (38.1% vs. 61.7%, p < 0.0001; 43.1% vs. 57.2%, p = 0.0002, respectively). Clinical trials from the USA had the least difference between sexes with an average of 46.7% females enrolled. Less females compared with males were enrolled in early-stage NSCLC (37.6% female vs. 62.6% male, p < 0.0001) and late-stage NSCLC trials (37.6% female vs. 62.0% male, p < 0.0001). CONCLUSIONS: Despite recent improvement, there continues to be significant underrepresentation of females compared with males in NSCLC clinical trials.

2024 Update of The Society of Thoracic Surgeons Short-term Esophagectomy Risk Model: More Inclusive and Improved Calibration.

BACKGROUND: The Society of Thoracic Surgeons General Thoracic Surgery Database (STS-GTSD) previously reported short-term risk models for esophagectomy for esophageal cancer. We sought to update existing models using more inclusive contemporary cohorts, with consideration of additional risk factors based on clinical evidence. METHODS: The study population consisted of adult patients in the STS-GTSD who underwent esophagectomy for esophageal cancer between January 2015 and December 2022. Separate esophagectomy risk models were derived for 3 primary end points: operative mortality, major morbidity, and composite morbidity or mortality. Logistic regression with backward selection was used, with predictors retained in models if P < .10. All derived models were validated using 9-fold cross-validation. Model discrimination and calibration were assessed for the overall cohort and specified subgroups. RESULTS: A total of 18,503 patients from 254 centers underwent esophagectomy for esophageal cancer. Operative mortality, morbidity, and composite morbidity or mortality rates were 3.4%, 30.5%, and 30.9%, respectively. Novel predictors of short-term outcomes in the updated models included body surface area and insurance payor type. Overall discrimination was similar or superior to previous STS-GTSD models for operative mortality (C statistic = 0.72) and for composite morbidity or mortality (C statistic = 0.62), Model discrimination was comparable across procedure- and demographic-specific subcohorts. Model calibration was excellent in all patient subgroups. CONCLUSIONS: The newly derived esophagectomy risk models showed similar or superior performance compared with previous models, with broader applicability and clinical face validity. These models provide robust preoperative risk estimation and can be used for shared decision making, assessment of provider performance, and quality improvement.

The Society of Thoracic Surgeons General Thoracic Surgery Database: 2023 Update on Outcomes and Research.

The Society of Thoracic Surgeons General Thoracic Surgery Database (GTSD) continues its trajectory of growth and enhancement, solidifying its stature as a premier global thoracic surgical database. The past year witnessed a notable expansion with the inclusion of 10 additional participating sites, now totaling 287, augmenting the database's repository to more than 800,000 procedures. A significant stride was made in refining the data audit process, thereby elevating the accuracy and completeness metrics, a testament to the relentless pursuit of data integrity. The GTSD further broadened its research apparatus, with 15 scholarly publications, a 50% uptick from the preceding year. These publications underscore the database's instrumental role in advancing thoracic surgical knowledge. In a concerted effort to alleviate data entry exigencies, the GTSD Task Force also instituted streamlined data submission protocols, a move lauded by participant sites. This report delineates the recent advancements, volume trajectories, and outcome metrics and encapsulates the prolific research output emanating from the GTSD, reflecting a year of substantial progress and academic fecundity.

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.

Baseline Electrocardiographic Abnormalities in Pre-Treatment Cancer Compared With Non-Cancer Patients: A Propensity Score Analysis.

Background: Most studies have compared post-treatment electrocardiogram (ECG) abnormalities in cancer patients to the general population. To assess baseline cardiovascular (CV) risk, we compared pre-treatment ECG abnormalities in cancer patients with a non-cancer surgical population. Methods: We conducted a combined prospective (n = 30) and retrospective (n = 229) cohort study of patients aged 18 - 80 years with diagnosis of hematologic or solid malignancy, compared with 267 pre-surgical, non-cancer, age- and sex-matched controls. Computerized ECG interpretations were obtained, and one-third of the ECGs underwent blinded interpretation by a board-certified cardiologist (agreement r = 0.94). We performed contingency table analyses using likelihood ratio Chi-square statistics, with calculated odds ratios. Data were analyzed after propensity score matching. Results: The mean age of cases was 60.97 ± 13.86; and 59.44 ± 11.83 years for controls. Pre-treatment cancer patients had higher likelihood of abnormal ECG (odds ratio (OR): 1.55; 95% confidence interval (CI): 1.05 to 2.30), and more ECG abnormalities (χ2 = 4.0502; P = 0.04) compared with non-cancer patients. ECG abnormalities were higher in black compared to non-black patients (P = 0.001). In addition, baseline ECGs among cancer patients prior to cancer therapy demonstrated less QT prolongation and intra-ventricular conduction defect (P = 0.04); but showed more arrhythmias (P < 0.01) and atrial fibrillation (AF) (P = 0.01) compared with the general patient population. Conclusions: Based on these findings, we recommend that all cancer patients receive an ECG, a low-cost and widely available tool, as part of their CV baseline screening, prior to cancer treatment.

Development of a Novel Circulating Autoantibody Biomarker Panel for the Identification of Patients with 'Actionable' Pulmonary Nodules.

Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology's Lung Imaging and Reporting Data System (Lung-RADS) 80-90% of patients screened will have clinically "non-actionable" nodules (Lung-RADS 1 or 2), and those harboring larger, clinically "actionable" nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations.

The Society of Thoracic Surgeons General Thoracic Surgery Database: 2022 Update on Outcomes and Research.

The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) remains the largest and most robust thoracic surgical database in the world. Participating sites receive risk-adjusted performance reports for benchmarking and quality improvement initiatives. The GTSD also provides several mechanisms for high-quality clinical research using data from 274 participant sites and 781,000 procedures since its inception in 2002. Participant sites are audited at random annually for completeness and accuracy. Over the last year and a half, the GTSD Task Force continued to refine the data collection process, implementing an updated data collection form in July 2021, ensuring high data fidelity while minimizing data entry burden. In addition, the STS Workforce on National Databases has supported a robust GTSD-based research program, which led to eight scholarly publications in 2021. This report provides an update on volume trends, outcomes, and database initiatives as well as a summary of research productivity resulting from the GTSD over the preceding year.

Predicting Non-home Discharge After Lung Surgery: Analysis of the General Thoracic Surgery Database.

BACKGROUND: Anticipating the need for non-home discharge (NHD) enables improved patient counseling and expedites placement, potentially reducing length of stay and hospital readmission. The objective of this study was to create a simple, preoperative, clinical prediction tool for NHD using The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD). METHODS: The STS GTSD was queried for patients who underwent elective anatomic lung cancer resection between 2009 and 2019. Exclusion criteria included age <18 years, percentage predicted diffusion capacity of the lung for carbon monoxide <20% or >150%, N3 or M1 disease, incomplete datasets, and mortality. The primary outcome was defined as discharge to an extended care, transitional care, rehabilitation center, or another hospital. Multivariable logistic regression was used to select risk factors and a nomogram for predicting risk of NHD was developed. The approach was cross-validated in 100 replications of a training set consisting of randomly selected two-thirds of the cohort and a validation set of remaining patients. RESULTS: A total of 35 948 patients from the STS GTSD met inclusion criteria. Final model variables used to derive the nomogram for NHD risk prediction included age (P < .001), percentage predicted diffusion capacity of the lung for carbon monoxide (P < .001), open surgery (P < .001), cerebrovascular history (P < .001), and Zubrod score (P < .001). The receiver operating characteristic curve, using sensitivities and specificities of the model, yielded area under the curve of 0.74. In 100 replicated cross-validations, out-of-sample area under the curve ranged from 0.72-0.76. CONCLUSIONS: Using readily available preoperative variables, our nomogram prognosticates the risk of NHD after anatomic lung resection with good discriminatory ability. Such risk stratification can enable improved patient counseling and facilitate better planning of patients' postoperative needs.

Conditional survival analysis of patients with resected non-small cell lung cancer.

Background: Conditional survival (CS) analyses provide an estimate of survival accounting for years already survived after treatment. We aim to evaluate the difference between actuarial and conditional survival in patients following lung resection for non-small cell lung cancer (NSCLC). In addition, CS analyses are used to examine whether prognosticators of survival change over time following surgery. Methods: Patients who underwent anatomic lung resection at a single institution for pathologic stage I-IIIA NSCLC between 2010 and 2021 were identified; those who underwent wedge resection for node-negative tumors ≤2 cm were also included. CS estimates were calculated as the probability of remaining disease-free after x years of nonrecurrence (CSx). Kaplan-Meier, log-rank, and Cox proportional hazard methods for examining CS were used for subgroup comparisons and assessing associations with baseline covariates. Results: Overall, 863 patients met the study inclusion criteria, with a median follow-up of 44.1 months. Conditional overall survival (OS) and disease-free survival (DFS) were greater than actuarial rates at all time points after surgery. At the time of resection, male sex (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.03 to 1.72; P = .032), tumor size >3 cm (HR, 1.17; 95% CI, 1.11-1.23; P < .001), node positivity (HR, 3.31; 95% CI, 2.52-4.33; P < .001), and American Joint Committee on Cancer stage (P < .001) were associated with DFS. However, if a patient lived 3 years without recurrence (CS3), these factors were no longer prognostic of DFS. Conclusions: Conditional survival analyses provide dynamic assessments of OS and DFS after NSCLC resection. After 3 years without recurrence, certain characteristics associated with DFS at the time of surgery no longer prognosticate recurrence.

The association between thoracic sarcopenia and survival is gender specific in early-stage lung cancer.

Background: Sarcopenia, as measured at the 3rd lumbar (L3) level, has been shown to prognosticate survival in cancer patients. However, many patients with early-stage non-small cell lung cancer (NSCLC) do not undergo abdominal imaging. We hypothesized that preoperative thoracic sarcopenia is associated with survival in patients undergoing lung resection for early-stage NSCLC. Methods: Patients who underwent anatomic resection for NSCLC between 2010-2019 were retrospectively identified. Exclusion criteria included induction therapy, less than 90 days of follow-up, and absence of computed tomography (CT) imaging. Cross sectional skeletal muscle area was calculated at the fifth thoracic vertebra (T5), twelfth thoracic vertebra (T12), and L3 level. Gender-specific lowest quartile values and previously defined values were used to define sarcopenia. Overall survival and disease-free survival were assessed using the Kaplan-Meier method. Results: Overall, 221 patients met inclusion criteria with a median body mass index (BMI) of 26.5 kg/m2 [interquartile range (IQR), 23.3-29.9 kg/m2], age of 69 years (IQR, 62.4-74.9 years), and follow-up of 46.9 months (IQR, 25.0-70.7 months). At the T5 level, sarcopenic males demonstrated worse overall survival [median 41.0 (IQR, 13.8-53.7) vs. 42.0 (IQR, 23.1-55.1) months, P=0.023] and disease-free survival [median 15.8 (IQR, 8.4-30.78) vs. 34.8 (IQR, 20.1-50.5) months, P=0.007] when compared to non-sarcopenic males. There was no difference in survival between sarcopenic and non-sarcopenic females when assessed at T5. Sarcopenia at T12 or L3 was associated with worse overall survival (P<0.05). Conclusions: Sarcopenia at T5 is associated with worse survival in males, but not females. When using upper thoracic vertebral levels to assess for sarcopenia, it is necessary to account for gender.

The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition.

There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.

Safety and efficacy of vagus nerve preservation technique during minimally invasive esophagectomy.

Background: This study aimed to assess the feasibility, efficacy and safety of McKeown surgery with vagal-sparing using minimally invasive esophagectomy (MIE). Methods: McKeown surgery with vagal-sparing technique using MIE was adopted on patients diagnosed with resectable esophageal cancer. From June 2020 to January 2021, a total of 20 patients from the Department of Thoracic Surgery of the National Clinical Research Center for Cancer were enrolled. Results: The study group included 17 (85%) males and 3 (15%) females, with an average age of 62.6 (±7.1) years. The most common tumor location was lower thoracic esophagus (n=9, 45%), followed by middle thoracic esophagus (n=8, 40%) and upper thoracic esophagus (n=3, 15%). Nine (45%) patients had T1b disease, followed by T2 (n=8, 40%), T1a (n=2, 10%), and Tis (n=1, 5%). The average operation time was 221.5 (±61.2) minutes. Postoperative complications were as follow: 2 (10%) with hoarseness, 2 (10%) with pulmonary infection, 1 (5%) with arrhythmia, 1 (5%) with anastomotic leakage, 1 (5%) with delayed gastric emptying, 1 (5%) with pleural effusion, and 1 (5%) with diarrhea. Dumping syndrome, cholestasis, and chylothorax were not observed, and there was no perioperative death. Conclusions: MIE with vagus nerve preservation is a feasible and safe technique, with the possibility to be an alternative for esophageal carcinoma. Further study is needed to explore the functional outcome of preserving vagus nerve.