Does Surgical Removal of the Thymus Have Deleterious Consequences?

The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy. We conclude that for patients with acetylcholine receptor antibody-positive MG and those diagnosed with thymoma, the removal of the thymus offers prominent benefits that well outweigh the potential risks. However, incidental removal of thymic tissue during other thoracic surgeries should be minimized whenever feasible.

Mitochondrial ncRNA LDL-805 declines in alveolar epithelial type 2 cells of chronic obstructive pulmonary disease patients.

Rationale: We showed that levels of a murine mitochondrial noncoding RNA, mito-ncR-LDL805 , increase in alveolar epithelial type 2 cells exposed to extracts from cigarette smoke. The transcripts translocate to the nucleus, upregulating nucleus-encoded mitochondrial genes and mitochondrial bioenergetics. This response is lost after chronic exposure to smoke in a mouse model of chronic obstructive pulmonary disease. Objectives: To determine if mito-ncR-LDL805 plays a role in human disease, this study aimed to (i) identify the human homologue, (ii) test if the smoke-induced response occurs in human cells, (ii) determine causality between the subcellular localization of the transcript and increased mitochondrial bioenergetics, and (iii) analyze mito-ncR-LDL805 transcript levels in samples from patients with chronic obstructive pulmonary disease. Methods: Levels and subcellular localization of the human homologue identified from an RNA transcript library were assessed in human alveolar epithelial type 2 cells exposed to smoke extract. Lipid nanoparticles were used for nucleus-targeted delivery of mito-ncR-LDL805 transcripts. Analyses included in situ hybridization, quantitative PCR, cell growth, and Seahorse mitochondrial bioenergetics assays. Measurements and Main Results: The levels of human homologue transiently increased and the transcripts translocated to the nuclei in human cells exposed to smoke extract. Targeted nuclear delivery of transcripts increased mitochondrial bioenergetics. Alveolar cells from humans with chronic obstructive pulmonary disease had reduced levels of the mito-ncR-LDL805 . Conclusions: mito-ncR-LDL805 mediates mitochondrial bioenergetics in murine and human alveolar epithelial type 2 cells in response to cigarette smoke exposure, but this response is likely lost in diseases associated with chronic smoking, such as chronic obstructive pulmonary disease, due to its diminished levels. Impact: This study describes a novel mechanism by which epithelial cells in the lungs adapt to the mitochondrial stress triggered by exposure to cigarette smoke. We show that a noncoding RNA in mitochondria is upregulated and translocated to the nuclei of alveolar epithelial type 2 cells to trigger expression of genes that restore mitochondrial bioenergetics. Mitochondria function and levels of the noncoding RNA decrease under conditions that lead to chronic obstructive pulmonary disease, suggesting that the mitochondrial noncoding RNA can serve as potential therapeutic target to restore function to halt disease progression.

Dedicated esophageal imaging may be unnecessary in marijuana-associated spontaneous pneumomediastinum: Findings from a retrospective cohort study.

Background: Marijuana use has become more common since its legalization, as have reports of marijuana-associated spontaneous pneumomediastinum. Non-spontaneous causes such as esophageal perforation are often ruled out on presentation due to the severe consequences of untreated disease. Here we seek to characterize the presentation of marijuana-associated spontaneous pneumomediastinum and explore whether esophageal imaging is necessary in the setting of an often benign course and rising healthcare costs. Materials and Methods: Retrospective review was performed for all 18-55 year old patients evaluated at a tertiary care hospital between 1/1/2008 and 12/31/2018 for pneumomediastinum. Iatrogenic and traumatic causes were excluded. Patients were divided into marijuana and control groups. Results: 30 patients met criteria, with 13 patients in the marijuana group. The most common presenting symptoms were chest pain/discomfort and shortness of breath. Other symptoms included neck/throat pain, wheezing, and back pain. Emesis was more common in the control group but cough was equally prevalent. Leukocytosis was present in most patients. Four out of eight of computed tomography esophagarams in the control group showed a leak requiring intervention, while only one out of five in the marijuana group showed even a possible subtle extravasation of contrast but this patient ultimately was managed conservatively given the clinical picture. All standard esophagrams were negative. All marijuana patients were managed without intervention. Discussion: Marijuana-associated spontaneous pneumomediastinum appears to have a more benign clinical course compared to non-spontaneous pneumomediastinum. Esophageal imaging did not change management for any marijuana cases. Perhaps such imaging could be deferred if clinical presentation of pneumomediastinum in the setting of marijuana use is not suggestive of esophageal perforation. Further research into this area is certainly worth pursuing.

Management of malignancy-induced, life-threatening hypoxemic respiratory failure using a self-expanding Y stent.

We present the case of a young woman transferred to our center with acute hypoxic respiratory failure due to an obstructing subcarinal mass. We review the management and rationale of this respiratory failure at different stages of her hospital course. We describe the approach and rationale in both the intensive care unit as well as the bronchoscopy suite. Finally, we discuss how the use of a novel hybrid Y stent effectively palliated her symptoms.

A Synthetic Small RNA Homologous to the D-Loop Transcript of mtDNA Enhances Mitochondrial Bioenergetics.

Mitochondrial malfunction is a hallmark of many diseases, including neurodegenerative disorders, cardiovascular and lung diseases, and cancers. We previously found that alveolar progenitor cells, which are more resistant to cigarette smoke-induced injury than the other cells of the lung parenchyma, upregulate the mtDNA-encoded small non-coding RNA mito-ncR-805 after exposure to smoke. The mito-ncR-805 acts as a retrograde signal between the mitochondria and the nucleus. Here, we identified a region of mito-ncR-805 that is conserved in the mammalian mitochondrial genomes and generated shorter versions of mouse and human transcripts (mmu-CR805 and hsa-LDL1, respectively), which differ in a few nucleotides and which we refer to as the "functional bit". Overexpression of mouse and human functional bits in either the mouse or the human lung epithelial cells led to an increase in the activity of the Krebs cycle and oxidative phosphorylation, stabilized the mitochondrial potential, conferred faster cell division, and lowered the levels of proapoptotic pseudokinase, TRIB3. Both oligos, mmu-CR805 and hsa-LDL1 conferred cross-species beneficial effects. Our data indicate a high degree of evolutionary conservation of retrograde signaling via a functional bit of the D-loop transcript, mito-ncR-805, in the mammals. This emphasizes the importance of the pathway and suggests a potential to develop this functional bit into a therapeutic agent that enhances mitochondrial bioenergetics.

Risk of Each of the Five Lung Lobectomies: A Society of Thoracic Surgeons Database Analysis.

BACKGROUND: The perioperative risk of pulmonary lobectomy as a solitary procedure has been extensively studied, yet the differences in outcomes between lobes, which have unique anatomy and a different amount of lung parenchyma, are entirely unknown. The purpose of this study was to define the risk of each of the 5 lobectomies. METHODS: The Society of Thoracic Surgeons Database was queried for patients undergoing lobectomy between 2008 and 2018. Patient and disease characteristics, operative variables, major morbidity, and 30-day mortality were examined. A multivariable logistic regression model (using the same variables in the current Society of Thoracic Surgeons lobectomy risk model) was developed to assess the contribution of lobectomy site to adverse outcomes. RESULTS: There were 65 006 patients analyzed. Adjusted perioperative mortality rate is lowest for right middle lobe (RML), 0.63%; intermediate for right upper lobe (RUL), left upper lobe (LUL), and left lower lobe (LLL), 1.08 to 1.24%; and highest for right lower lobe (RLL), 1.63%. The adjusted major morbidity rate is lowest for RML, 5.36%; intermediate for LLL and LUL, 7.82% to 8.33%; and highest for RUL and RLL, 8.94% to 9.32%. Adjusted intraoperative transfusion rate is lowest for RML, 1.37%; intermediate for RLL and LLL, 1.81% to 1.94%; and highest for RUL and LUL, 2.47% to 2.72%. CONCLUSIONS: There are clear differences in postoperative outcomes by lobectomy location. Mortality, major morbidity, and transfusion rate are lowest for RML but vary across other lobectomies. These differences should be appreciated in evaluating risk of operation, deciding on best therapy, counseling patients, and comparing outcomes.

Drain Amylase: A Simple and Versatile Method of Detecting Esophageal Anastomotic Leaks.

BACKGROUND: Anastomotic leak after esophagectomy is a significant cause of morbidity. Perianastomotic drain amylase is accurate in detecting leaks, but it is unclear whether its accuracy is affected by comorbid conditions, anastomotic method, or anastomotic location. We hypothesized that drain amylase would accurately discriminate leak in a variety of settings. METHODS: We reviewed 290 consecutive patients undergoing esophagectomy with gastric conduit reconstruction. Patient comorbidities, operative variables, and drain amylase were collected. The diagnosis of a leak was based on the level of intervention required, and was characterized as clinically significant if it required wound opening or endoscopic or surgical intervention. Receiver-operating characteristic curves analysis was performed to determine the accuracy of amylase to detect leak for each patient variable. RESULTS: A total of 53 (18.3%) of 290 esophagectomies had an anastomotic leak, of which 33 (11.4%) of 290 were clinically significant. Drain amylase was a strong predictor of anastomotic leak on postoperative day (POD) 3 to POD 7, regardless of patient comorbidities, location of anastomosis, or technique of anastomosis, but was less accurate in the diagnosis of leak in current smokers (area under the receiver-operating characteristic curve, 0.530 vs 0.752; P = .006). A maximum drain amylase value no higher than 35 on POD 3, POD 4, or POD 5 was 88% sensitive in detecting leak at any point postoperatively. A value greater than or equal to 150 was 88% specific in diagnosing leak. CONCLUSIONS: Drain amylase is a versatile method for early detection of anastomotic leaks. Its accuracy is unaffected by neoadjuvant treatment, location or type of anastomosis, or patient comorbidities but may be less accurate in active smokers.

Surgery following neoadjuvant chemoradiation therapy in clinical N3 esophageal cancer results in improved survival: a propensity-matched analysis.

Esophageal cancer patients with extensive nodal metastases have poor survival, and benefit of surgery in this population is unclear. The aim of this study is to determine if surgery after neoadjuvant chemoradiotherapy (nCRT) improves overall survival (OS) in patients with clinical N3 (cN3) esophageal cancer relative to chemoradiation therapy (CRT) alone. The National Cancer Database was queried for all patients with cN3 esophageal cancer between 2010 and 2016. Patients who met inclusion criteria (received multiagent chemotherapy and radiation dose ≥30 Gy) were divided into two cohorts: CRT alone and nCRT + surgery. 769 patients met inclusion criteria, including 560 patients who received CRT alone, and 209 patients who received nCRT + surgery. The overall 5-year survival was significantly lower in the CRT alone group compared to the nCRT + surgery group (11.8% vs 18.0%, P < 0.001). A 1:1 propensity matched cohort of CRT alone and nCRT + surgery patients also demonstrated improved survival associated with surgery (13.11 mo vs 23.1 mo, P < 0.001). Predictors of survival were analyzed in the surgery cohort, and demonstrated that lymphovascular invasion was associated with worse survival (HR 2.07, P = 0.004). Despite poor outcomes of patients with advanced nodal metastases, nCRT + surgery is associated with improved OS. Of those with cN3 disease, only 27% underwent esophagectomy. Given the improved OS, patients with advanced nodal disease should be considered for surgery. Further investigation is warranted to determine which patients with cN3 disease would benefit most from esophagectomy, as 5-year survival remains low (18.0%).

Robotic minimally invasive esophagectomy provides superior surgical resection.

INTRODUCTION: Robotic minimally invasive esophagectomy (RMIE) and "traditional" minimally invasive esophagectomy techniques (tMIE) have reported superior outcomes relative to open techniques. Differences in the outcomes of these two approaches have not been examined. We hypothesized that short-term outcomes of RMIE would be superior to tMIE. METHODS AND PROCEDURES: The National Cancer Database was used to analyze outcomes of patients undergoing RMIE and tMIE from 2010 to 2016. Patients with clinical metastatic disease were excluded. Trends in the number of procedures performed with each approach were described using linear regression testing. Primary outcome of interest was 90-day mortality rate. Secondary outcomes of interest were positive surgical margin rate, number of lymph nodes (LN) removed, adequate lymphadenectomy (> 15 LNs), length of hospitalization (LOS), readmission rate, and conversion to open rate. Outcomes of RMIE and tMIE were compared using Wilcoxon rank sum test and chi square test as appropriate. Multivariable regression was also performed to reduce the impact of differences in the cohorts of patients receiving RMIE and tMIE. RESULTS: 6661 minimally invasive esophagectomies were performed from 2010 to 2016 (1543/6661 (23.2%) RMIE and 5118/6661 (76.8%) tMIE). Over the study period, the proportion of RMIE increased from 10.4% (64/618) in 2010 to 27.2% (331/1216) in 2016 (p < 0.001) (Fig. 1). The primary outcome of 90-day mortality was similar between RMIE and tMIE (92/1170 (7.4%) vs 305/4148 (7.9%), p = 0.558) (Table 2). RMIE and tMIE also had similar readmission rate (6.3 vs 7%, p = 0.380). There was no difference between the cohorts based on sex, age, race, insurance, and tumor size. The cohorts of patients receiving RMIE and tMIE differed in that RMIE patients had lower rates of elevated Charlson scores, were more likely to be treated at an academic institution, had a higher rate of advanced clinical T-stage and clinical nodal involvement, and had received neoadjuvant therapy. In a univariate analysis, RMIE had a lower rate of positive margin (3.9 vs 6.1%, p = 0.001), more mean lymph nodes evaluated (16.6 ± 9.74 vs 16.1 ± 10.08 p = 0.018), lower conversion to open rate (5.4 vs 11.4%, p < 0.001), and a shorter mean length of stay (12.1 ± 10.39 vs 12.8 ± 11.18 days, p < 0.001). In multivariable analysis, RMIE was associated with lower risk of conversion to open (OR 0.51, 95% CI: 0.37-0.70, p < 0.001) and lower rate of positive margin (OR 0.62, 95% CI: 0.41-0.93, p = 0.021).). Additionally, in a multivariable logistic regression, RMIE demonstrated superior adequate lymphadenectomy (> 15 LNs) (OR 1.18, 95% CI 1.02-1.37, p < 0.032). CONCLUSION: In the National Cancer Database, robotic esophagectomy is associated with superior rate of conversion to open and positive surgical margin status. We speculate enhanced dexterity and visualization of RMIE facilitates intraoperative performance leading to improvement in these outcomes.

Antibiotic Resistance Is Associated With Morbidity and Mortality After Decortication for Empyema.

BACKGROUND: Previous studies of decortication for empyema demonstrated that patient characteristics are associated with mortality, but the relationship of infectious pathogen to outcome has not been described. Our objective was to analyze the association of microbiology and antibiotic resistance with postoperative mortality after decortication for empyema. We hypothesized that bacterial pathogens, antibiotic resistance, and patient characteristics would all contribute to perioperative morbidity and mortality. METHODS: Patients undergoing pulmonary decortication for empyema from January 1, 2010 to October 1, 2017 were reviewed retrospectively. Cases were matched with microbiology cultures. Outcomes of interest were a composite of death, tracheostomy, initial ventilator support greater than 48 hours, or unexpected intensive care unit readmission. Antibiotic resistance was categorized as present or absent, and the number of antibiotics with resistance was counted for each patient. We describe the relationship of patient characteristics, antibiotic resistance, and microbiology to mortality. RESULTS: During the study period, 185 patients underwent decortication, 118 of whom had a diagnosis of primary empyema (63.8%). Positive culture results were present in 79 of 185 patients (43%). The most common isolate was Streptococcus, which was present in 29 of 79 (37%), followed by Staphylococcus in 19 of 79 (24%). Of 79 patients, 11 had fungal infections (13.9%). In addition, 16 of 79 patients had polymicrobial empyema (20%). Of 185 patients, 30 experienced the composite adverse outcome (16.2%). In multivariable regression, the composite adverse outcome was associated with emphysema, Candida in pleural culture, and antibiotic resistance count. CONCLUSIONS: Perioperative mortality and morbidity after decortication for empyema is considerable. In this cohort, infections with increasing antibiotic resistance are associated with morbidity and mortality among patients with empyema.

Factors Associated With Successful Postoperative Day One Discharge After Anatomic Lung Resection.

BACKGROUND: There are no criteria to estimate the risk of early discharge after anatomic lung resection. We hypothesized that demographic, clinical, and surgical variables could be used to predict successful postoperative day 1 (POD1) discharge after anatomic lung resection. METHODS: Patients with POD1 discharge after anatomic lung resection were identified in The Society of Thoracic Surgeons database from 2012 to 2018. Discharges were categorized as successful based on freedom from complications, readmission, or death. A multivariable model identified variables from univariate analysis and was further optimized using stepwise selection. This model was used to create a risk score of success. RESULTS: Among 62,785 patients who underwent anatomic lung resection, 2480 (3.9%) were discharged on POD1. Of the 2480 patients, 2129 (85.8%) had successful discharge and 351 (14.2%) had failed discharge due to postoperative complication (282; 11.3%), readmission (151; 6.1%), or death (9; 0.4%). In univariable analysis, successful POD1 discharge was associated with younger age, female sex, video-assisted thoracic surgery, higher forced expiratory volume in 1 second and diffusion capacity of lung for carbon monoxide, shorter operating room times, and lower rates of comorbidities. A risk model for successful discharge incorporated sex, age, body mass index, operative lobe, Zubrod score, American Society of Anesthesiologists class, coronary artery disease, chronic obstructive pulmonary disease, video-assisted thoracic surgery approach, and operating room time. Using this model, a risk score created, and derived estimated proportion of successful POD1 discharge varied from 75.6% to 92.9%. CONCLUSIONS: Demographic, clinical, and surgical variables are associated with successful POD1 discharge. This analysis suggests that a combination of demographic factors is associated with failed early discharge, and this understanding can be used in conjunction with clinical judgment to facilitate decisions regarding appropriateness of POD1 discharge.

Neoadjuvant Treatment Is Associated With Superior Outcomes in T4 Lung Cancers With Local Extension.

BACKGROUND: Neoadjuvant chemoradiation is associated with improved survival of superior sulcus cancers, but little data exists regarding clinical T4 lung cancers with mediastinal invasion. We hypothesized that neoadjuvant treatment would be associated with improved survival in T4 lung cancer patients with mediastinal invasion. METHODS: Clinical T4-N0/1-M0 non-small cell lung cancers from 2006-2015 were identified in the National Cancer Database. Patients with T4 extension to mediastinal structures undergoing lobectomy, bilobectomy, or pneumonectomy were included. Neoadjuvant treatment was defined as preoperative chemotherapy and/or radiation. Patients receiving surgery >120 days after radiation were excluded. Study endpoints were pathologic margin status and overall survival. To adjust for heterogeneity, a 1:1 propensity match analysis was performed. RESULTS: A total of 1101 patients with cT4N0/1M0 cancers were analyzed; 595 (54.0%) received primary surgery and 506 (46.0%) received neoadjuvant treatment. Neoadjuvant therapy was associated with fewer positive surgical margins (46 of 506 [9.3%] vs 186 of 595 [33.1%], P < .001). Multivariate analysis showed an association of neoadjuvant therapy with a lower rate of positive margin (odds ratio 0.220, P < .001). Overall survival was longer among patients receiving neoadjuvant treatment (65.9 vs 27.5 months, P < .001). Propensity matching identified 331 matched pairs of patients. Among these, positive margins were less likely after receiving neoadjuvant treatment (10.5% vs 31.3%, P < .001). Overall survival among the matched pairs was improved in those receiving neoadjuvant treatment (57.0 vs 27.5 months, P < .001). CONCLUSIONS: In the NCDB, T4N0/1 mediastinal invasion patients who receive neoadjuvant treatment have decreased rates of positive surgical margins and improved overall survival. The use of neoadjuvant treatment should be considered in these patients.

Conventional Computed Tomographic Calcium Scoring vs full chest CTCS for lung cancer screening: a cost-effectiveness analysis.

BACKGROUND: Conventional CTCS images the mid/lower chest for coronary artery disease (CAD). Because many CAD patients are also at risk for lung malignancy, CTCS often discovers incidental pulmonary nodules (IPN). CTCS excludes the upper chest, where malignancy is common. Full-chest CTCS (FCT) may be a cost-effective screening tool for IPN. METHODS: A decision tree was created to compare a FCT to CTCS in a hypothetical patient cohort with suspected CAD. (Figure) The design compares the effects of missed cancers on CTCS with the cost of working up non-malignant nodules on FCT. The model was informed by results of the National Lung Screening Trial and literature review, including the rate of malignancy among patients receiving CTCS and the rate of malignancy in upper vs lower portions of the lung. The analysis outcomes are Quality-Adjusted Life Year (QALY) and incremental cost-effectiveness ratio (ICER), which is generally considered beneficial when <$50,000/QALY. RESULTS: Literature review suggests that rate of IPNs in the upper portion of the lung varied from 47 to 76%. Our model assumed that IPNs occur in upper and lower portions of the lung with equal frequency. The model also assumes an equal malignancy potential in upper lung IPNs despite data that malignancy occurs 61-66% in upper lung fields. In the base case analysis, a FCT will lead to an increase of 0.03 QALYs comparing to conventional CTCS (14.54 vs 14.51 QALY, respectively), which translates into an QALY increase of 16 days. The associated incremental cost for FCT is $278 ($1027 vs $748, FCT vs CTCS respectively. The incremental cost-effectiveness ratio (ICER) is $10,289/QALY, suggesting significant benefit. Sensitivity analysis shows this benefit increases proportional to the rate of malignancy in upper lung fields. CONCLUSION: Conventional CTCS may be a missed opportunity to screen for upper lung field cancers in high risk patients. The ICER of FCT is better than screening for breast cancer screening (mammograms $80 k/QALY) and colon cancer (colonoscopy $6 k/QALY). Prospective studies are appropriate to define protocols for FCT.

Minimally invasive esophagectomy is associated with superior survival, lymphadenectomy and surgical margins: propensity matched analysis of the National Cancer Database.

Despite excellent short-term outcomes of minimally invasive esophagectomy (MIE), there is minimal data on long-term outcomes compared to open esophagectomy. MIE's superior visualization may have improved lymphadenectomy and complete resection rate and therefore improved long-term outcomes. We hypothesized that MIE would have superior long-term survival. Patients undergoing an esophagectomy for cancer between 2010 and 2016 were identified in the National Cancer Database. MIE included laparoscopic/robotic approach, and conversions were categorized as open. A 1:1 propensity match was performed. Lymphadenectomy and margin status were compared between MIE and open using Stuart Maxwell marginal homogeneity and Wilcoxon matched-pair signed-rank test. Survival was compared using log-rank test. 13,083 patients were identified: 8,906 (68%) open and 4,177 (32%) MIE. Propensity matching identified 3,659 'pairs' of MIE and open esophagectomy patients. Among them, MIE was associated with higher number lymph nodes examined (16 vs. 14, P < 0.001) and similar number of positive lymph nodes (0 vs. 0, P = 0.33). MIE had higher rate of negative pathologic margin (95 vs. 93.5%, P < 0.001). MIE was also associated with shorter hospitalization (9 vs. 10 days, P < 0.001). Survival was improved among MIE patients (46.6 vs. 41.4 months for open, P = 0.003) and among pathologic node-negative patients (71.4 vs. 61.5 months, P = 0.005). These data suggest that MIE has improved short-term outcomes (improved lymphadenectomy, pathologic margins, and length of stay) and also associated improved overall survival. The etiology of superior overall survival is likely secondary to many factors related and unrelated to surgical approach.

Mortality After Esophagectomy: Analysis of Individual Complications and Their Association with Mortality.

BACKGROUND: The relationship between individual complications and esophagectomy mortality is unclear. The influence of comorbidities on the impact of complications on operative mortality is also unknown. We sought to assess the impact of individual complications and the effect of coexisting comorbidities on operative mortality following esophagectomy. METHODS: All gastric conduit esophagectomies performed for cancer from 2008 to 2017 in the Society of Thoracic Surgery database were identified. Chi square was utilized to identify postoperative events associated with operative mortality. Multivariable logistic regression analysis was performed, utilizing postoperative events, to determine the risk-adjusted effect on operative mortality for each postoperative event. To assess the effect of preoperative comorbidities, a second logistic regression analysis was performed, incorporating preoperative characteristics. RESULTS: Of 11,943 esophagectomy patients, 63.9% had a postoperative event and 3.3% died, which did not change over the study period. The postoperative events with the highest impact on operative mortality were respiratory distress syndrome (OR 7.48 (95% CI 5.23-10.7)), reintubation (OR 6.55 (4.61-9.30)), and renal failure (OR 5.97 (4.08-8.75)). Anastomotic leak requiring reoperation was associated with increased operative mortality (OR 1.48 (1.03-2.14)), but medically managed leak was not. Incorporating preoperative characteristics into the operative mortality model had little effect on odds ratio for death for individual postoperative events. CONCLUSIONS: In the Society of Thoracic Surgery database, 64% of patients suffer postoperative events and 3.3% die following esophagectomy. The independent association of certain postoperative events with mortality is an objective method of terming a complication "major" and may aid efforts to reduce mortality.

Postoperative day 1 discharge after anatomic lung resection: A Society of Thoracic Surgeons database analysis.

OBJECTIVE: Although minimally invasive techniques have led to shorter hospitalizations, discharge on postoperative day 1 is still uncommon. We hypothesized that day 1 discharge could be performed safely and that there might be significant variation in day 1 discharge rates between hospitals. METHODS: We identified patients with lung cancer who underwent lobectomy and segmentectomy in the Society of Thoracic Surgeons Database from 2012 to 2017. The 10% longest hospital stay outliers were excluded. A multivariable regression model was created to assess for factors associated with day 1 discharge and readmission. RESULTS: A total of 46,325 patients were examined, and 1821 patients (3.9%) were discharged on day 1. This rate increased from 3.4% to 5.3% over the course of the study (P < .0001). In multivariable analysis, factors associated with day 1 discharge included age, Zubrod score, body mass index greater than 25, forced expiration value at 1 second, middle or upper lobectomy, minimally invasive technique, and procedure time. Outpatient 30-day mortality was similar (0.3% vs 0.4%, P = .472). Patients discharged on day 1 were not at increased risk of readmission. Readmission after day 1 discharge was associated with male sex, coronary artery disease, chronic obstructive pulmonary disease, and longer procedure time. There was substantial variation in day 1 discharge rate between institutions, with 11 centers (4.0%) discharging more than 20% of their patients on day 1, whereas 102 centers (36.7%) had no day 1 discharges. CONCLUSIONS: Day 1 discharge after anatomic lung resection is uncommon but is becoming more common. Carefully selected patients may be discharged on day 1 without an increased risk of readmission or death.

Higher Doses of Neoadjuvant Radiation for Esophageal Cancer Do Not Affect the Pathologic Complete Response Rate or Survival: A Propensity-Matched Analysis.

BACKGROUND: Traditional neoadjuvant therapy for esophageal cancer has used chemoradiation doses greater than 45 Gy. This study aimed to examine the dose of preoperative radiation in relation to the pathologic complete response (pCR) rate and overall survival (OS) for patients with resectable esophageal cancer. METHODS: The National Cancer Database was queried for all patients with esophageal or gastroesophageal junction cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy between 2006 and 2015. The radiation doses were divided into four ranges based on Grays (Gy) received: less than 39.6 Gy, 39.60-44.99 Gy, 45-49.99 Gy, and 50 Gy or more. RESULTS: The inclusion criteria were met by 10,293 patients. All patients received neoadjuvant CRT, with 689 patients (6.7%) receiving less than 39.6 Gy, 973 patients (9.5%) receiving 39.6-44.9 Gy, 3837 patients (37.3%) receiving 45-49.9 Gy, and 4794 patients (46.6%) receiving 50 Gy or more. The overall pCR rate was 17.2% (1769/10,293) and was significantly lower for those who received less than 39.6 Gy of radiation than for those who received 39.6 Gy or more (13.9% [96/689] vs. 17.4% [1673/9604]; p = 0.017). The median OS of 37.2 months was significantly better for those who received 39.6 Gy or more than for those who received less than 39.6 Gy (38 vs. 29.6 months (p < 0.0001). The pCR and OS did not differ between the three higher radiation doses (39.6-44.9 vs. 45-49.9 Gy vs. ≥ 50 Gy; pCR [p = 0.1] vs. OS [p = 0.097]). The patients who received 39.6-44.9 Gy were propensity matched with those who received 45 Gy or more of radiation. There remained no difference in pCR (p = 0.375) or OS (p = 0.957). CONCLUSIONS: In the United States, the heterogeneity in neoadjuvant CRT dosing is significant, with 84% of patients receiving more than 45 Gy. The benefit of neoadjuvant CRT in terms of pCR and overall  survival is seen with doses of 39.6 Gy or more, but not with doses higher than 45 Gy.

Desaturation during Six-Minute Walk Testing Predicts Major Morbidity Following Anatomic Lung Resection among Patients with COPD.

BACKGROUND: Pulmonary function testing (PFT) is commonly used to risk-stratify patients prior to lung resection. Guidelines recommend that patients with reduced lung function, due to chronic lung conditions such as Chronic Obstructive Pulmonary Disease (COPD), should receive additional physiologic testing to determine fitness for resection. We reviewed our experience with six-minute walk testing (SMWT) to determine the association of test results and post-operative complications. METHODS: Consecutive adult patients undergoing segmentectomy, lobectomy, bilobectomy or pneumonectomy between 1 January, 2007 and 1 January, 2017 were identified in a prospectively maintained database. Patients with poor lung function, as defined by percent predicted forced expiratory volume in 1 s (FEV1) or diffusion capacity of carbon monoxide (DLCO) ≤60%, had results of SMWT extracted from their chart. Association of test result to post-operative events was performed. RESULTS: 581 patients had anatomic lung resections with predicted post-operative FEV1 or DLCO values ≤60%, consistent with a diagnosis of COPD. Among them, 50 (8.6%) had preoperative SMWT performed. Patients who received SMWT were more likely to have a FEV1 or DLCO less than 40 percent predicted (24/50 (48.0%) vs 166/531 (31.3%), p = 0.016). Post-operatively, patients who had SMWT performed had higher rates of pneumonia, but similar rates of major morbidity. The post-exercise oxygen saturation and the amount of desaturation correlated with the occurrence of major morbidity. In multivariable regression, oxygen desaturation was an independent risk factor for the occurrence of major morbidity, and desaturation was an excellent predictor of major morbidity by receiver operating characteristic curves analsysis. CONCLUSIONS: Among patients with elevated risk, oxygen desaturation during SMWT was independently associated with the occurence of major morbidity in multivariable analysis, while pulmonary function testing was not. SMWT is an important tool for risk-stratification, and may be underutilized.