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BH3 mimetic drugs, which inhibit prosurvival BCL2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL1 inhibitors, we demonstrate that concurrent MEK + MCL1 inhibition induces apoptosis and tumor regression in KRAS-mutant non–small cell lung cancer (NSCLC) models, which respond poorly to MEK inhibition alone. Susceptibility to BH3 mimetics that target either MCL1 or BCL-xL was determined by the differential binding of proapoptotic BCL2 proteins to MCL1 or BCL-xL, respectively. The efficacy of dual MEK + MCL1 blockade was augmented by prior transient exposure to BCL-xL inhibitors, which promotes the binding of proapoptotic BCL2 proteins to MCL1. This suggests a novel strategy for integrating BH3 mimetics that target different BCL2 family proteins for KRAS-mutant NSCLC.Significance:Defining the molecular basis for MCL1 versus BCL-xL dependency will be essential for effective prioritization of BH3 mimetic combination therapies in the clinic. We discover a novel strategy for integrating BCL-xL and MCL1 inhibitors to drive and subsequently exploit apoptotic dependencies of KRAS-mutant NSCLCs treated with MEK inhibitors.See related commentary by Leber et al., p. 1511.This article is highlighted in the In This Issue feature, p. 1494

Supplementary Figure 1-5, Supplementary Tables 1-3

BACKGROUND Airway release (AR) maneuvers performed during airway resection to reduce anastomotic tension have not been thoroughly studied. METHODS This study retrospectively analyzed consecutive resections for postintubation stenosis (PITS) and primary tracheal neoplasms (PTNs) at Massachusetts General Hospital (Boston, MA). Anastomotic complications were defined as stenosis, separation, necrosis, granulation tissue, and air leak. Logistic regression modeling was used to identify factors associated with AR and adverse outcome. RESULTS From 1993 to 2019, 545 patients with PITS (375; 68.8%) and PTNs (170; 31.2%) underwent laryngotracheal, tracheal, or carinal (resections and reconstructions; 5.7% (31 of 545) were reoperations. AR was performed in 11% (60 of 545): in 3.8% of laryngotracheal resections (6 of 157; all laryngeal), in 9.8% of tracheal resections (34 of 347; laryngeal, 12, and hilar, 22), and in 49% of carinal resections (20 of 41; laryngeal, 1, and hilar, 19). Mean resected length was 3.5 cm (range, 1to- 6.3 cm) with AR and 3.0 cm (range, 0.8 to 6.5 cm) without AR (P < .01). Operative mortality was 0.7% (4 of 545); all 4 anastomoses were intact until death. Anastomotic complications were present in 5% of patients who underwent AR (3 of 60) and in 9.3% (45 of 485) of patients who did not. AR was associated with resection length of 4 cm or longer (odds ratio [OR], 6.15; 95% confidence interval [CI], 1.37 to 27.65), PTNs (OR, 7.81; 95% CI, 3.31 to 18.40), younger age (OR, 0.96; 95% CI, 0.94 to 0.98), and lung resection (OR, 6.09; 95% CI, 1.33 to 27.90). Anastomotic complications in patients with tracheal anastomoses were associated with preexisting tracheostomy (OR, 2.68; 95% CI, 1.50 to 4.80), but not release. CONCLUSIONS Tracheal reconstruction succeeds, even when anastomotic tension requires AR. Because intraoperative assessment may underestimate tension, lowering the threshold for AR seems prudent, particularly in patients with diabetes.

Minimally invasive surgical approaches for extended pulmonary resections are becoming increasingly common as more surgeons gain experience in thoracoscopic and robotic technique. Outcome studies demonstrate improved decreased morbidity as compared with an open surgery.

Background The oncologic efficacy of segmentectomy is controversial. We compared long-term survival in clinical stage IA (T1N0) Medicare patients undergoing lobectomy and segmentectomy in The Society of Thoracic Surgeons database. Methods The Society of Thoracic Surgeons General Thoracic Surgery Database was linked to Medicare data in 14,286 lung cancer patients who underwent segmentectomy (n = 1654) or lobectomy (n = 12,632) for clinical stage IA disease from 2002 to 2015. Cox regression was used to create a long-term survival model. Patients were then propensity matched on demographic and clinical variables to derive matched pairs. Results In Cox modeling segmentectomy was associated with survival similar to lobectomy in the entire cohort (hazard ratio, 1.04; 95% confidence interval, 0.89-1.20; P = .64) and in the matched subcohort. A subanalysis restricted to the 2009 to 2015 population (n = 11,811), when T1a tumors were specified and positron emission tomography results and mediastinal staging procedures were accurately recorded in the database, also showed that segmentectomy and lobectomy continue to have similar survival (hazard ratio, 1.00; 95% confidence interval, 0.87-1.16). Subanalysis of the pathologic N0 patients demonstrated the same results. Conclusions Lobectomy and segmentectomy for early-stage lung cancer are equally effective treatments with similar survival. Surgeons from The Society of Thoracic Surgeons database appear to be selecting patients appropriately for sublobar procedures.

Objectives The study objectives were to evaluate the immediate, short-, and medium-term efficacy and safety of pulmonary artery branch sealing using an ultrasonic vessel-sealing device in minimally invasive anatomic lung resection. Methods This study consists of a prospective, phase 2, multicenter, international clinical trial (clinicaltrials.gov: NCT02719717) that enrolled patients planned for video-assisted thoracoscopic surgery/robotic anatomic lung resection in 7 centers (United States, Canada, United Kingdom). Pulmonary artery branches of 7 mm or less were sealed and divided with an ultrasonic energy vessel-sealing device. The remainder of the lobectomy was performed according to surgeon preference. Intraoperative, in-hospital, and 30-day postoperative bleeding and complications were prospectively recorded. Results A total of 150 patients with a minimum of 1 pulmonary artery branch sealed with an ultrasonic vessel-sealing device were prospectively enrolled in the trial. Resections included 139 lobectomies and 11 segmentectomies. A total of 424 pulmonary artery branches were divided: 239 with the ultrasonic vessel-sealing device, 181 with endostaplers, and 4 with endoscopic clips. The mean and median pulmonary artery diameters were 4.7 mm/5.0 mm, 10.3 mm/10.0 mm, and 6.5 mm/6.5 mm for each method, respectively. Three of the pulmonary artery branches divided with the ultrasonic vessel-sealing device (1.3%) and 4 pulmonary artery branches divided with endostaplers (2.2%) bled intraoperatively. Among the patients with seal failures, 1 patient required conversion to thoracotomy. There was no postoperative bleeding from divided pulmonary artery branches with either sealing method. There was no mortality at 30 days. Conclusions Pulmonary artery branch sealing with ultrasonic energy during video-assisted thoracoscopic surgery lobectomy is safe for vessels 7 mm or less. The use of an ultrasonic device is a reasonable sealing method for pulmonary artery branches 7 mm or less.

Minimally invasive surgical approaches for extended pulmonary resections are becoming increasingly common as more surgeons gain experience in thoracoscopic and robotic technique. Outcome studies demonstrate improved decreased morbidity as compared with an open surgery.

Background The practice of overlapping surgery impacts patients, providers, and policy-makers. While several studies have examined the relationship between overlapping surgery and clinical outcomes, a combined analysis of all available data has not been performed. We aimed to evaluate the impact of overlapping surgery on 30-day mortality, morbidity, and length of surgery. Methods A systematic literature review revealed all relevant studies examining outcomes of overlapping versus non-overlapping surgery as of March 2018. A pooled meta-analysis with stratification by study quality grade was performed, and heterogeneity and publication bias were assessed. Results A total of 14 sets of analyses met inclusion and exclusion criteria. Meta-analysis revealed no significant differences in 30-day mortality (OR = 0.84; p = 0.277) or overall morbidity (OR = 0.96; p = 0.632) between patients who underwent overlapping versus non-overlapping surgery. The standardized mean difference for length of surgery between the groups indicated a small statistically significant increase in length of surgery for the overlapping surgery group (SMD = 0.079, p Conclusion While further study is warranted, current literature suggests that overlapping surgery is not associated with increased risk of mortality or morbidity.

The clinical impact of a positive radial margin after esophagectomy for cancer has not been clearly identified. The goal of this study was to identify risk factors for a positive radial margin and determine the impact on recurrence and survival. Retrospective review of 196 patients with pathological T3 N0-3 esophageal adenocarcinoma undergoing esophagectomy between 2002 and 2017. Mortality data was extracted from Electronic Medical Records and Social Security Death Index. Mean age was 63.7 ± 11.4 years, and there were 166 (84.7%) men. Neoadjuvant therapy was given in 141(71.9%) patients. We identified 29(14.8%) patients with a positive radial margin. Factors significantly associated with a positive radial margin include not receiving neoadjuvant therapy and presence of lymphatic, vascular, or perineural invasion. Overall, there were 94(48%) recurrences during a mean follow-up of 24.7 months. Involvement of the radial margin was not significantly associated with recurrence-free survival (HR 1.24, CI 95% 0.73–2.12, p = 0.425). Overall survival for the entire cohort was 41.6% and 28.9% at 3 and 5 years, respectively. Involvement of the radial margin did not have a significant impact on overall survival (HR 1.23, CI 95% 0.68–2.22, p = 0.493). The likelihood of encountering a positive margin is associated with lack of neoadjuvant treatment and the presence of lymphatic, vascular, or perineural invasion in the esophagectomy specimen. An involved radial margin after esophagectomy for locally advanced cancer was not associated with tumor recurrence or overall survival in our cohort, and other factors such as lymph node involvement are stronger in determining outcome.

The purpose of this study was to quantify the cost impact of complications of esophagectomy and identify opportunities for reducing costs while optimizing outcomes. Patients undergoing esophagectomy at a single institution between 2002 and 2017 were included. Complications were tabulated from clinical data. Direct hospital costs were determined for all encounters between the day of surgery and postoperative day 90. Risk factors were assessed using logistic regression. The relative incremental cost of complications was assessed using multivariable linear regression. A total of 761 patients were included in this study. 428 patients (56%) experienced at least 1 complication. Factors associated with increased likelihood of complications included age (P0.001), female sex (P = 0.005), pack-years (P = 0.006), cerebrovascular disease (P = 0.021), and diabetes (P = 0.052). The most common complications were atrial arrhythmia (18%), transfusion (15%), and atelectasis requiring bronchoscopy (8%). The complications incurring the greatest incremental cost per event were anastomotic complications requiring surgical treatment (200%, P0.001) or those treated nonoperatively (96%, P0.001), and renal failure (178%, P0.001). Pneumonia increased costs by 40% (P0.001) and other major pulmonary complications increased costs by 75% (P0.001). Though the cost of complications was unaffected by surgical approach (minimally invasive esophagectomy vs open), MIE was associated with decreased cost vis-à-vis a lower complication rate (41% vs 60%, P0.001). Complications accounted for 28% of the aggregate 90-day direct hospital cost for all patients. Pulmonary complications accounted for 35% of all complication-attributable costs, while anastomotic complications accounted for 17%. Anastomotic and pulmonary complications after esophagectomy with gastric conduit reconstruction represent high-yield targets for cost reduction and quality improvement.

Background Post-esophagectomy tracheo-bronchial-esophageal fistula (PETEF) most often develops after anastomotic disruption or gastric conduit necrosis. Ideal surgical management and outcomes for this complication are uncertain. Methods A retrospective review of 11 patients undergoing surgical repair of PETEF was performed. Results The median time between esophagectomy and surgical repair of PETEF was 61 days (range, 7 days to 28 years). Anastomotic leak or gastric conduit necrosis was responsible for PETEF in 6 patients (54.5%), whereas other causes were erosion of a tracheal appliance (n = 2), gastric conduit staple line erosion (n = 1), anastomotic stricture dilation (n = 1), and recurrent esophageal cancer (n = 1). Membranous airway defects were repaired primarily and buttressed with muscle or omental flaps in 8 patients (72.7%), whereas two (18.2%) were repaired with bio-prosthetic patches and one (9.1%) was repaired with a sleeve resection of the bronchus. Anastomotic and neo-esophageal conduit defects were repaired primarily in 3 patients (27.3%), whereas 7 patients (63.6%) underwent conduit take-down and esophageal or pharyngeal diversion, and 1 patient (9.1%) underwent simultaneous fistula repair and colon interposition. Two patients (18.2%) had recurrent fistulas, with 1 patient dying after second fistula closure and the other was discharged with no further attempt at repair. Three patients (27.3%) died postoperatively. Only 3 patients (27.3%) resumed an oral diet after fistula repair. Conclusions Surgical treatment is effective for most patients undergoing operative repair of PETEF, notwithstanding a considerable risk of postoperative morbidity and death. Although fistula repair is life saving and prevents further respiratory deterioration, return to oral alimentation is not ensured.

BH3 mimetic drugs, which inhibit prosurvival BCL2 family proteins, have limited single-agent activity in solid tumor models. The potential of BH3 mimetics for these cancers may depend on their ability to potentiate the apoptotic response to chemotherapy and targeted therapies. Using a novel class of potent and selective MCL1 inhibitors, we demonstrate that concurrent MEK + MCL1 inhibition induces apoptosis and tumor regression in KRAS-mutant non–small cell lung cancer (NSCLC) models, which respond poorly to MEK inhibition alone. Susceptibility to BH3 mimetics that target either MCL1 or BCL-xL was determined by the differential binding of proapoptotic BCL2 proteins to MCL1 or BCL-xL, respectively. The efficacy of dual MEK + MCL1 blockade was augmented by prior transient exposure to BCL-xL inhibitors, which promotes the binding of proapoptotic BCL2 proteins to MCL1. This suggests a novel strategy for integrating BH3 mimetics that target different BCL2 family proteins for KRAS-mutant NSCLC. Significance: Defining the molecular basis for MCL1 versus BCL-xL dependency will be essential for effective prioritization of BH3 mimetic combination therapies in the clinic. We discover a novel strategy for integrating BCL-xL and MCL1 inhibitors to drive and subsequently exploit apoptotic dependencies of KRAS-mutant NSCLCs treated with MEK inhibitors. See related commentary by Leber et al., p. 1511. This article is highlighted in the In This Issue feature, p. 1494

Rationale: Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. High-resolution computed tomography has limited resolution, and surgical lung biopsy (SLB) carries risks of morbidity and mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis. Objectives: We performed a prospective diagnostic accuracy study of EB-OCT in patients with ILD with a low-confidence diagnosis undergoing SLB. The primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern. Methods: EB-OCT was performed immediately before SLB. The resulting EB-OCT images and histopathology were interpreted by blinded, independent pathologists. Clinical diagnosis was obtained from the treating pulmonologists after SLB, blinded to EB-OCT. Measurements and Main Results: We enrolled 31 patients, and 4 were excluded because of inconclusive histopathology or lack of EB-OCT data. Twenty-seven patients were included in the analysis (16 men, average age: 65.0 yr): 12 were diagnosed with UIP and 15 with non-UIP ILD. Average FVC and Dl(CO) were 75.3% (SD, 18.5) and 53.5% (SD, 16.4), respectively. Sensitivity and specificity of EB-OCT was 100% (95% confidence interval, 75.8–100.0%) and 100% (79.6–100%), respectively, for both histopathologic UIP and clinical diagnosis of IPF. There was high agreement between EB-OCT and histopathology for diagnosis of ILD fibrosis pattern (weighted κ: 0.87 [0.72–1.0]). Conclusions: EB-OCT is a safe, accurate method for microscopic ILD diagnosis, as a complement to high-resolution computed tomography and an alternative to SLB.

Summary Background Esophageal perforation is a morbid condition and remains a therapeutic challenge. We report the outcomes of a large institutional experience with esophageal perforation and identify risk factors for morbidity and mortality. Methods A retrospective analysis was conducted on 142 patients who presented with a thoracic or gastroesophageal junction esophageal perforation from 1995 to 2020. Baseline characteristics, operative or interventional strategies, and outcomes were analyzed by etiology of the perforation and management approach. Multivariable cox and logistic regression models were constructed to identify predictors of mortality and morbidity. Results Overall, 109 (77%) patients underwent operative intervention, including 80 primary reinforced repairs and 21 esophagectomies and 33 (23%) underwent esophageal stenting. Stenting was more common in iatrogenic (27%) and malignant (64%) perforations. Patients who presented with a postemetic or iatrogenic perforation had similar 90-day mortality (16% and 16%) and composite morbidity (51% and 45%), whereas patients who presented with a malignant perforation had a 45% 90-day mortality and 45% composite morbidity. Risk factors for mortality included age >65 years (hazard ratio [HR] 1.89 [1.02–3.26], P = 0.044) and a malignant perforation (HR 4.80 [1.31–17.48], P = 0.017). Risk factors for composite morbidity included pleural contamination (odds ratio [OR] 2.06 [1.39–4.43], P = 0.046) and sepsis (OR 3.26 [1.44–7.36], P = 0.005). Of the 33 patients who underwent stent placement, 67% were successfully managed with stenting alone and 30% required stent repositioning. Conclusions Risk factors for morbidity and mortality after esophageal perforation include advanced age, pleural contamination, septic physiology, and malignant perforation. Primary reinforced repair remains a reasonable strategy for patients with an esophageal perforation from a benign etiology.

Early, accurate diagnosis of interstitial lung disease (ILD) is critical for clinical management and therapeutic decision-making, especially distinguishing idiopathic pulmonary fibrosis (IPF) from non-IPF ILD. Unfortunately, current diagnostic imaging methods are limited in resolution and surgical biopsy methods are invasive. In this study, we evaluate the accuracy of endobronchial optical coherence tomography (EB-OCT) as a low-risk method for in vivo ILD diagnosis in patients undergoing surgical biopsy. EB-OCT was able to distinguish diagnostic microanatomical features of IPF from non-IPF ILDs, independently compared against surgical biopsy. These findings support the potential of OCT as a minimally-invasive method for IPF diagnosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal form of fibrotic interstitial lung disease (ILD). Early diagnosis of IPF is essential, but often requires invasive surgery. We conduct a prospective study evaluating the diagnostic accuracy of endobronchial optical coherence tomography (EB-OCT) for IPF diagnosis as compared to concurrent surgical lung biopsy (SLB) and clinical follow-up diagnosis. EB-OCT was performed immediately prior to SLB in 27 ILD patients. EB-OCT was 100% sensitive and 100% specific for both histologic and clinical follow up diagnosis of IPF. The results demonstrate the potential of EB-OCT as minimally-invasive, low-risk in vivo method for microscopic IPF diagnosis.

Indications for exploring the mediastinum in the setting of thyroid and parathyroid disease include benign substernal goiter, thyroid malignancy, metastatic lymph nodes arising from thyroid malignancy, and mediastinal parathyroid adenoma. Although these mediastinal pathologies can often be resected through a transcervical approach, a thoracic approach to the mediastinum may be required for complete exposure and resection depending on the lesion’s size, location, and relationship to adjacent structures. These thoracic approaches can include full sternotomy, partial sternotomy, trapdoor incision, and thoracotomy as well as minimally invasive approaches such as mediastinoscopy, thoracoscopy, and robot-assisted thoracoscopic surgery. In cases where a thoracic approach may be required, preoperative consultation and intraoperative collaboration with a cardiothoracic surgeon can facilitate an optimal approach for resection of these intrathoracic mediastinal pathologies.

Approximately 10% to 15% of patients with solitary fibrous tumors of the pleura (SFTP) have recurrence after resection. Many are not candidates for reresection and lack effective treatments. We explored the expression of programmed death ligand 1 (PD-L1) as a biomarker for candidacy for treatment with immune checkpoint inhibitors.We reviewed the medical records of 52 patients with primary SFTP and 5 with recurrent SFTP. We performed immunohistochemistry on tumor tissue to determine the expression of PD-L1 and infiltration by cluster of differentiation 8 (CD8)-positive immune cells.Any PD-L1 expression was observed in 11 primary SFTP (21.2%). Overall, PD-L1 expression level was less than 1% in 10 patients (19.2%) and greater than 1% in 1 (1.9%). Tumor infiltration by CD8-positive immune cells was absent or rare in 13 patients (25%), less than 5% in 31 (59.6%), and 5% to 25% in 8 (15.4%). There were no associations between PD-L1 expression or immune cell infiltrates and known risk factors for recurrence or a prognostic risk score classification. Time to recurrence was strongly associated with the risk score classification (P.001), but it was not associated with PD-L1 expression (P = .296) or immune cell infiltrates (P = .619). In recurrent SFTP, PD-L1 was expressed in 4 of 10 tumors (40%; all1% expression). There was no correlation in PD-L1 expression between primary and recurrent SFTP samples.A small subset of SFTP express PD-L1 at low levels (1%) but exhibit colocalization of CD8-positive immune cells suggesting an inducible expression mechanism. The role of PD-L1 merits exploration in the clinical setting in patients with advanced SFTP when alternative treatments or clinical trials are considered.

Background Costs related to care of patients who undergo lobectomy for lung cancer may vary depending on patient, disease, and treating facility characteristics. We aimed to identify underlying case mix factors that contribute to variability of 90-day costs of lobectomy for early-stage lung cancer. Methods The Society of Thoracic Surgeons General Thoracic Surgery Database was queried for lobectomy for clinical stage I lung cancer (2008-2013). Demographics, clinical outcomes, and 90-day episode-of-care costs across all care settings were analyzed for patients successfully linked to Medicare data. Hospital costs were estimated from charges using cost-to-charge ratios. Comprehensive regression models were created to identify impact of preoperative patient factors and hospital characteristics on costs, and to delineate additive costs due to perioperative outcomes and complications. Results The mean 90-day cost for lobectomy was $45,080 ± $38,239. Variables associated with significant additive costs were age greater than or equal to 75 years, American Society of Anesthesiologists classification III or IV, forced expiratory volume in 1 second less than 80% predicted, body mass index less than 18.5 or greater than 35, current or past smoker, cerebrovascular disease, chronic kidney disease, impaired functional status, open thoracotomy, prolonged operative time, government hospitals, metropolitan setting, and geographic location. Patients with 1 or more postoperative complication resulted in an overall mean added cost of $27,259. Added costs increased with the number of complications; isolated recurrent laryngeal nerve paresis ($3,911) and respiratory failure ($35,011) were associated with the least and most additive cost, respectively. Conclusions Lobectomy is associated with substantial variability of episode-of-care costs. Variability is driven by patient demographic and clinical factors, hospital characteristics, and the occurrence and severity of complications.

OBJECTIVES Idiopathic laryngotracheal stenosis (ILTS) is an uncommon problem arising mostly in women. In some, it arises during or is exacerbated by pregnancy. Experience with management of patients with this rare association is limited. This study seeks to evaluate the management of patients with pregnancy-associated ILTS and compare outcomes to cases not associated with pregnancy. METHODS Retrospective review of 15 patients undergoing surgical treatment of pregnancy-associated ILTS from 1971 to 2013. Variables of interest and airway outcomes were compared to patients with non-pregnancy-associated ILTS. RESULTS Pregnancy-associated ILTS was observed in 15/263 (5.7%) patients. Symptoms developed during their first pregnancy. When compared to non-pregnancy patients, these patients were younger (37 vs 47 years; P = 0.0003), had more prior tracheostomies (26.7% vs 10.9%; P = 0.085) and had more preoperative airway dilatations (86.7% vs 57.7%; P = 0.030). All patients completed pregnancy without complications and ultimately underwent laryngotracheal resection. The expression of hormonal receptors in the surgical specimens was similar in both groups (oestrogen receptors: 100% vs 75% and progesterone receptors: 71.4% vs 72.1%, in pregnancy and non-pregnancy patients, respectively). Airway outcomes were good/excellent in 13 (86.7%) patients with pregnancy-associated ILTS and 225 (90.7%) patients without pregnancy association (P = 0.642), and did not change when adjusting for other risk factors. CONCLUSIONS Pregnancy-associated ILTS is rare. The pathophysiology is unclear, but appearance of symptoms during pregnancy may suggest hormonal factors. To minimize foetal risk, dilatation during pregnancy followed by laryngotracheal resection after delivery is the preferred treatment. Pregnancy association does not seem to affect outcomes with expected satisfactory results in most patients.

Background The longitudinal cost of treating patients with non-small cell lung cancer (NSCLC) undergoing surgical resection has not been evaluated. We describe initial and 4-year resource use and cost for NSCLC patients aged 65 years of age or greater who were treated surgically between 2008 and 2013. Methods Using clinical data for NSCLC resections from The Society of Thoracic Surgeons General Thoracic Surgery Database linked to Medicare claims, resource use and cost of preoperative staging, surgery, and subsequent care through 4 years were examined ($2017). Cost of hospital-based care was estimated using cost-to-charge ratios; professional services and care in other settings were valued using reimbursements. Inverse probability weighting was used to account for administrative censoring. Outcomes were stratified by pathologic stage and by surgical approach for stage I lobectomy patients. Results Resection hospitalizations averaged 6 days and cost $31,900. In the first 90 days, costs increased with stage ($12,430 for stage I to $26,350 for stage IV). Costs then declined toward quarterly means more similar among stages. Cumulative costs ranged from $131,032 (stage I) to $205,368 (stage IV). In the stage I lobectomy cohort, patients selected for minimally invasive procedures had lower 4-year costs than did thoracotomy patients ($120,346 versus $136,250). Conclusions The 4-year cost of surgical resection for NSCLC was substantial and increased with pathologic stage. Among stage I lobectomy patients, those selected for minimally invasive surgery had lower costs, particularly through 90 days. Potential avenues for improving the value of surgical resection include judicious use of postoperative intensive care and earlier detection and treatment of disease.

Context.—Lesion localization during intraoperative frozen section of lung resection specimens can be challenging. Imaging could aid lesion localization while enabling 3-dimensional specimen analysis.Objective.—To assess the feasibility of integrating micro–computed tomography (micro-CT) into the perioperative evaluation of fresh surgical lung resection specimens.Design.—Fresh lung specimens from patients with a presumptive diagnosis of lung cancer were imaged with micro-CT prior to routine histopathologic and molecular analysis. Micro-CT images were assessed to determine image quality, lesion size, and distance from lesion to the nearest surgical margin. Micro-CT measurements were compared to pathologic measurements using Bland-Altman analysis.Results.—A total of 22 specimens from 21 patients were analyzed (mean image acquisition time, 13 ± 6 minutes). Histologic quality of imaged specimens was indistinguishable from a control group of nonimaged lung specimens. Artifacts, most commonly from specimen deflation (n = 8), obscured fine detail on micro-CT images of 10 specimens. Micro-CT could successfully localize the target lesion in the other 12 specimens. Distance to the nearest surgical margin was determined in 10 specimens. Agreement of micro-CT with final pathology was good, with a mean difference of −2.8% (limits of agreement −14.5% to 20.0%) for lesion size and −0.5 mm (limits of agreement −4.4 to 3.4 mm) for distance to nearest surgical margin.Conclusions.—Micro-CT of fresh surgical lung specimens is feasible and has the potential to evaluate the size and location of lesions within resection specimens, as well as distance to the nearest surgical margin, all without compromising specimen integrity.

Purpose The prevalence of minimally invasive lung cancer surgery using video-assisted thoracic surgery (VATS) has increased dramatically over the past decade, yet recent studies have suggested that the lymph node evaluation during VATS lobectomy is inadequate. We hypothesized that the minimally invasive approach to lobectomy for stage I lung cancer resulted in a longitudinal outcome that was not inferior to thoracotomy. Patients and Methods Patients > 65 years of age who had undergone lobectomy for stage I lung cancer between 2002 and 2013 were analyzed within the Society of Thoracic Surgeons General Thoracic Surgery Database, which had been linked to Medicare data, as part of a retrospective-cohort, noninferiority study. Results A total of 10,597 patients with clinical stage I lung cancer who underwent lobectomy were evaluated (4,448 patients underwent thoracotomy, and 6,149 underwent VATS). VATS patients had a more favorable distribution of all health-related variables, including pulmonary function (59% of VATS patients had intact spirometry v 51% of thoracotomy patients; P < .001). Cox proportional hazards models were performed over two eras to account for an evolving practice standard. The mortality risk associated with the VATS approach was not greater than thoracotomy in either the earlier era (2002 to 2008; hazard ratio, 0.97; 95% CI, 0.87 to 1.09; P = .62) or the more recent era (2009 to 2013; hazard ratio, 0.84; 95% CI, 0.75 to 0.93; P < .001). Kaplan-Meier survival estimates of 2,901 propensity-matched VATS-thoracotomy pairs demonstrated that the 4-year survival associated with VATS (68.6%) was modestly superior to thoracotomy (64.8%; P = .003). The analyses detailed above were replicated in a separate cohort of pathologic stage I patients with similar findings. Conclusion The long-term efficacy of lobectomy for stage I lung cancer performed using the VATS approach by board-certified thoracic surgeons does not seem to be inferior to that of thoracotomy.

Tracheobronchomalacia is an uncommon acquired disorder of the central airways. Common symptoms include dyspnea, constant coughing, inability to raise secretions, and recurrent respiratory infections. Evaluation includes an inspiratory-expiratory chest CT (dynamic CT), an awake functional bronchoscopy, and pulmonary function studies. Patients with significant associated symptoms and severe collapse on CT and bronchoscopy are offered membranous wall plication. Tracheobronchoplasty is performed through a right thoracotomy. The posterior airway is exposed after the azygous vein is ligated. Patients report generally good results with improvement of their symptoms. Quality of life is usually improved, whereas pulmonary function tests usually are not improved.

Modern thoracic surgery requires knowledge and skill in advanced bronchoscopic techniques. Rigid bronchoscopy remains a workhorse for the management of central airway obstruction. Dilation of tracheal strictures is now much simpler with the advent of the balloon dilator, which can be passed through a therapeutic bronchoscope. Numerous adjuncts, such as laser, argon beam coagulation, electrocautery, and cryotherapy, can be used to improve airway patency. There are now numerous stenting options for strictures that require stenting to maintain airway patency.

For nearly 15 years The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) has provided participating institutions with risk-adjusted feedback reports that allow outcome comparisons relative to national benchmarks. With more than 300 contributing centers across North America, the STS GTSD now includes more than 530,000 cases. In 2017 the STS GTSD Task Force revised the data collection form with the goal of collecting more detailed and accurate information for the most important thoracic surgical cases without increasing the workload of registrars. In addition, the learning curve for thoracoscopic lobectomy was examined, online public reporting was initiated, institutional feedback reports were made more user-friendly, and collaboration with the European Society of Thoracic Surgery continued. The STS GTSD Task Force continues to work to improve the quality of care and support research initiatives in general thoracic surgery. This report summarizes current aggregate national outcomes in general thoracic surgery and reviews related activities in the areas of quality measurement, performance improvement, and transparency from the STS GTSD during the past 12 months.

Background Prior risk models using the STS General Thoracic Surgery database (STS-GTSD) have been limited to 30-day outcomes. We have now linked STS data to Medicare data and sought to create a risk prediction model for long-term mortality after lung cancer resection in patients older than 65 years. Methods The STS-GTSD was linked to Medicare data for lung cancer resections from 2002 to 2013 as previously reported. Successful linkage was performed in 29,899 lung cancer resection patients. Cox proportional hazards modeling was used to create a long-term survival model. Variable selection was performed using statistically significant univariate factors and known clinical predictors of outcome. Calibration was assessed by dividing the cohort into deciles of predicted survival and discrimination assessed with a C-statistic corrected for optimism via 1,000 bootstrap replications. Results Median age was 73 years (interquartile range, 68 to 78 years), and 48% of the patients were male. Of the 29,094 patients with nonmissing pathologic stage, 69% were stage I, 18% stage II, 11% stage III, and 2% stage IV. Procedure performed was lobectomy in 69%, bilobectomy in 3%, pneumonectomy in 3%, segmentectomy in 7%, sleeve lobectomy in 1%, and wedge resection in 17%. Thoracoscopic approach was performed in 47% of resections. The final Cox model reveals that stage and age are the strongest predictors of long-term survival. Even after controlling for stage, wedge resection, segmentectomy, bilobectomy, and pneumonectomy are all associated with increased hazard of death in comparison with lobectomy. Thoracoscopic approach is associated with improved long-term survival in comparison with thoracotomy. Other modifiable predictive factors include smoking and low body mass index. Calibration of the model demonstrates excellent performance across all survival deciles and a C-statistic of 0.694. Conclusions The STS-GTSD-Medicare long-term risk model includes several novel factors associated with mortality. Although medical factors predict long-term survival, age and stage are the strong predictors. Despite this, procedure choice and thoracoscopic/open approach are potentially modifiable predictors of long-term survival after lung cancer resection.

Background Epiphrenic esophageal diverticula are infrequent. Although surgical treatment is generally recommended, technique varies widely and optimal management remains controversial. This study evaluated a single-institution experience for surgical treatment of epiphrenic diverticula. Methods A retrospective review was made of medical records of 31 patients undergoing surgical treatment for epiphrenic diverticula from 1974 to 2016. Results There were 17 men (55%); median age was 65 years. Dysphagia (87%) and regurgitation (71%) were the most common symptoms. Three patients (10%) presented acutely: 2 with ruptured diverticula and 1 with hematemesis. All patients underwent an open transthoracic approach. Diverticulectomy was performed in 28 patients (90%), myotomy in 28 (90%), and a concomitant antireflux procedure in 6 (19%). A total of 22 patients (71%) underwent diverticulectomy and myotomy, 4 (13%) underwent diverticulectomy with myotomy and antireflux procedure, 2 (6%) had myotomy and antireflux, 2 had diverticulectomy alone, and 1 patient had imbrication of the diverticulum after myotomy. Overall, morbidity occurred in 11 patients (35.5%), with major morbidity in 6 (19.4%). There was one postoperative esophageal leak (3%). Ninety-day mortality was zero. Mean follow-up was 30 ± 43 months in 28 patients. Additional procedures (ie, reoperation, balloon dilation) were needed in 7 patients (25%). An excellent outcome (ie, absence of symptoms) was accomplished in 21 patients (75%). Acute presentation was associated with need for further procedures ( p = 0.011) and symptoms at follow-up ( p = 0.011). Conclusions A tailored transthoracic approach to the surgical management of epiphrenic diverticula can provide excellent results. The need for a concomitant antireflux procedure remains controversial and may not be routinely necessary. Acute presentation is associated with poor functional outcome.

Straight back syndrome is a rare condition usually associated with mitral valve prolapse and "pseudo-heart disease" caused by a very narrow anterior-posterior chest due to the loss of the normal dorsal curvature of the thoracic spine. More rarely, the narrowed upper chest may compress the trachea causing extrinsic tracheal obstruction. If severe enough, this requires operative repair by effectively opening up the upper chest by a variety of techniques to allow the trachea enough room to avoid compression.

Background The Society of Thoracic Surgeons (STS) has developed composite quality measures for cardiac surgical procedures and lobectomy for lung cancer. This study sought to develop a composite measure for esophagectomy for esophageal cancer. Methods The STS esophagectomy composite score is derived from two risk-adjusted outcomes: mortality and major complications. General Thoracic Surgery Database data were included from 2012 to 2014, and 95% Bayesian credible intervals were established to determine "star" ratings. STS participants were compared with the National Inpatient Sample as a national benchmark (including non-STS participants). Results The study population included 4,321 patients who underwent esophagectomy from 167 participating centers. The operative mortality rate was 3.1% (N = 135), and the major complication rate was 33.1% (N = 1,429). Of the 167 participants, 70 reported an average yearly volume of five or more esophagectomies during the study period. With this threshold, reliability for the composite score was 0.58 (95% credible interval, 0.41 to 0.72). Of these 70 participants, 5 (7.1%) were three star, 63 (90.0%) were two star, and 2 (2.9%) were one star. A majority of STS participants, 58.1% (N = 97), did not have sufficient volume to receive a reliable composite score. Benchmarked to the 2012 National Inpatient Sample cohort, STS General Thoracic Surgery Database participants have comparable discharge mortality rates and shorter postoperative lengths of stay. Conclusions STS has developed a quality measure for esophageal cancer surgical procedures based on a composite score of risk-adjusted operative mortality rates and major complications. The composite rating for esophagectomy has good reliability for programs performing an average of five procedures annually, although almost 60% of participants are not eligible for a star rating because of lower procedure volumes.

The art and science of outcomes analysis, quality improvement, and patient safety continue to evolve, and cardiothoracic surgery leads many of these advances. The Society of Thoracic Surgeons (STS) National Database is one of the principal reasons for this leadership role, as it provides a platform for the generation of knowledge in all of these domains. Understanding these topics is a professional responsibility of all cardiothoracic surgeons. Therefore, beginning in January 2016, The Annals of Thoracic Surgery began publishing a monthly series of scholarly articles on outcomes analysis, quality improvement, and patient safety. This article provides a summary of the status of the STS National Database as of October 2016 and summarizes the articles about the STS National Database that appeared in The Annals of Thoracic Surgery 2016 series, "Outcomes Analysis, Quality Improvement, and Patient Safety."

OBJECTIVES Failure of anastomotic healing is a morbid complication after airway or oesophageal surgery. Hyperbaric oxygen therapy (HBOT) has been used extensively in the management of complex wound-healing problems. We demonstrate the use of HBOT to rescue at-risk anastomoses or manage anastomotic failures in thoracic surgery. METHODS Retrospective review of 25 patients who received HBOT as part of the management of tracheal or oesophageal anastomotic problems during 2007–2018. HBOT was delivered at 2 atm with 100% oxygen in 90-min sessions. RESULTS Twenty-three patients underwent airway resection and reconstruction while 2 patients underwent oesophagectomy. There were 16 (70%) laryngotracheal and 7 (30%) tracheal resections. Necrosis at the airway anastomosis was found in 13 (57%) patients, partial dehiscence in 2 (9%) patients and both in 6 (26%) patients. HBOT was prophylactic in 2 (9%) patients. Patients received a median of 9.5 HBOT sessions (interquartile range 5–19 sessions) over a median course of 8 days. The airway anastomosis healed in 20 of 23 (87%) patients. Overall, a satisfactory long-term airway outcome was achieved in 19 (83%) patients; 4 patients failed and required reoperation (2 tracheostomies and 1 T-tube). HBOT was used in 2 patients after oesophagectomy to manage focal necrosis or ischaemia at the anastomosis, with success in 1 patient. Complications from HBOT were infrequent and mild (e.g. ear discomfort). CONCLUSIONS HBOT should be considered as an adjunct in the management of anastomotic problems after airway surgery. It may also play a role after oesophagectomy. Possible mechanisms of action are rapid granulation, early re-epithelialization and angiogenesis.

Background Surgeons are prone to feelings of sadness, guilt, and anxiety when involved in major adverse events. We aimed to create and evaluate a second victim peer support program for surgeons and surgical trainees. Study Design The second victim peer support program was an intervention performed in the Department of Surgery at a tertiary care academic medical center. Surgical attendings and trainees participated as peer supporters or affected peers. In this article, we describe the design of the program and its 1-year impact, which was evaluated through the number of interventions attempted and realized and feedback received from all participants using an anonymous qualitative and quantitative survey. Results The program was established using the following 5 steps: creation of a conceptual framework, choice of peer supporters, training of peer supporters, multifaceted identification of major adverse events, and design of a systematic intervention plan. In 1 year, the program had 47 interventions distributed evenly between attendings and trainees; 19% of affected peers opted out of receiving support. Most participants expressed satisfaction with the program's confidentiality, the safe/trusting environment it provided, and the timeliness of the intervention (89%, 73%, and 83%, respectively); 81% suggested that the program had a positive impact on the department's “safety and support” culture and would recommend the program to a colleague. Several areas for improvement were identified, including the need to improve identification of events requiring outreach, and the desire for increased awareness of the program throughout the department. Conclusions We successfully designed, implemented, and assessed the impact of the first surgery-specific peer support program in the US. Our 1-year experience suggests that the program is highly used and well received, albeit with opportunities for improvement.

INTRODUCTION Diversion of excess prescription opioids contributes to the opioid epidemic. We sought to describe and study the impact of a comprehensive departmental initiative to decrease opioid prescribing in surgery. METHODS A multispecialty multidisciplinary initiative was designed to change the culture of postoperative opioid prescribing, including: consensus-built opioid guidelines for 42 procedures from 11 specialties, provider-focused posters displayed in all surgical units, patient opioid/pain brochures setting expectations, and educational seminars to residents, advanced practice providers, residents and nurses. Pre- (April 2016-March 2017) versu post-initiative (April 2017-May 2018) analyses of opioid prescribing at discharge [median oral morphine equivalent (OME)] were performed at the specialty, prescriber, patient, and procedure levels. Refill prescriptions within 3 months were also studied. RESULTS A total of 23,298 patients were included (11,983 pre-; 11,315 post-initiative). Post-initiative, the median OME significantly decreased for 10 specialties (all P values < 0.001), the percentage of patients discharged without opioids increased from 35.7% to 52.5% (P < 0.001), and there was no change in opioids refills (0.07% vs 0.08%, P = 0.9). Similar significant decreases in OME were observed when the analyses were performed at the provider and individual procedure levels. Patient-level analyses showed that the preinitiative race/sex disparities in opioid-prescribing disappeared post-initiative. CONCLUSION We describe a comprehensive multi-specialty intervention that successfully reduced prescribed opioids without increase in refills and decreased sex/race prescription disparities.

Previous "high-stakes" examinations by the American Board of Thoracic Surgery (ABTS) required remote testing, were noneducational, and were not tailored to individual practices. Given the ABTS mission of public safety and diplomate education, the ABTS Maintenance of Certification (MOC) examination was revised in 2015 to improve the educational experience and validate knowledge acquired.The ABTS-MOC Committee developed a web-based, secure examination tailored to the specialty-specific practice profile (cardiac, general thoracic, cardiothoracic, congenital) of the individual surgeon. After an initial answer to each question, an educational critique was reviewed before returning to the initial question and logging a second (final) response. Intraexam learning was assessed by comparing scores before and after reading the critique. Diplomate feedback was obtained.A total of 988 diplomates completed the 10-year MOC examination between 2015 and 2017. Substantive learning was demonstrated with an 18%, 17%, 20%, and 9% improvement in cardiac, general thoracic, cardiothoracic, and congenital final scores, respectively. This improvement was most notable among diplomates with the lowest initial scores. Fewer diplomates failed the new exam (1% vs 2.3%). Diplomate postexam survey highlighted marked improvements in clinical relevance (35% vs 78%), convenience (37% vs 78%), and learning (15% vs 45%). Over 80% acknowledged educational value, and 97% preferred the new format.The new MOC process demonstrates increased knowledge acquisition through a convenient, secure, web-based practice-focused examination. This approach provides feedback, identifies baseline knowledge gaps for individual diplomates, and validates new knowledge attained.

Background To evaluate the management, complications of treatment, and outcomes of postintubation tracheal stenosis. Methods A retrospective review was performed of records from a prospective database of all patients undergoing tracheal or laryngotracheal resection from 1993 to 2017 for postintubation tracheal stenosis. Redo operations after failure of initial resection and reconstruction for postintubation tracheal stenosis were included. Results There were 392 patients whose ages ranged from 3 months to more than 84 years. A tracheostomy was performed in 275 as part of their care before surgery (present at time of resection in 123), dilations in 201, laser treatment in 82, T tubes in 66, and stents in 44 patients. Median length of resection was 3 cm. Laryngeal release was required in 15 of 392 (3.8%). Operative mortality was 0.8% (3 of 392); T tubes, tracheostomy present at resection, requirement for postoperative tracheostomy, and laryngeal involvement adversely impacted outcomes. Patients having tracheal resection and reconstruction had good or satisfactory outcomes in 96% (289 of 301) compared with 85% (77 of 91) having laryngotracheal resection. Complications within 30 days and at more than 30 days occurred in 116 patients and 14 patients, respectively. There were 96 anastomotic complications—68% minor (65 of 96), and 32% major (31 of 96). Necrosis of cartilage occurred in 12 patients and dehiscence in 14 patients. Conclusions Despite advances in care postintubation tracheal stenosis remains a challenging problem. Laryngotracheal resection and tracheostomy lead to worse outcomes. Excellent surgical results can be obtained for postintubation tracheal stenosis. Good results require careful evaluation, management of comorbid conditions, meticulous technique, minimizing tension, and preservation of blood supply.

Chronic thromboembolic pulmonary hypertension is an uncommon but increasingly recognized surgically treatable cause of pulmonary hypertension. Diagnosis is often delayed when patients present with unexplained exertional dyspnea in the absence of obvious cardiopulmonary disease. The standard evaluation process includes an echocardiogram, a ventilation perfusion scan, chest computed tomography angiography, and a right heart catheterization with a pulmonary angiogram. Most patients have surgically accessible disease when evaluated by an experienced hypertension team. The operation is standardized and performed through a median sternotomy, with standard bicaval and aortic cannulation. Hypothermic circulatory arrest is used to ensure a bloodless field. The key to the operation is selecting the proper dissection plane between the intima and the media, which allows the surgeon to dissect the specimen far out into the segmental and subsegmental pulmonary artery vessels. Anticoagulation is started early postoperatively as soon as mediastinal chest tube output is minimal. Most patients have a good result and operative mortality is now under 5% in most centers.