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Long-term survival of lung transplants lags behind other solid organs due to early onset of a fibrotic form of chronic rejection known as chronic lung allograft dysfunction (CLAD). Preventing CLAD is difficult as multiple immunologic and physiologic insults contribute to its development. Targeting fibroblast activation, which is the final common pathway leading to CLAD, offers the opportunity to ameliorate fibrosis irrespective of the initiating insult. Thy-1 is a surface glycoprotein that controls fibroblast differentiation and activation.To study the role of Thy-1 in CLAD, we utilized the minor antigen mismatched C57BL/6 (B6More severe CLAD was evident in B6Our findings suggest that the loss of Thy-1 on fibroblasts is a previously unrecognized cause of CLAD and its replacement may offer therapeutic applications for amelioration of this disease post-transplantation in the setting of infectious stress responses.

Objective On November 24, 2017, Organ Procurement and Transplantation Network implemented a change to lung allocation replacing donor service area with a 250 nautical mile radius around donor hospitals. We sought to evaluate the experience of a small to medium size center following implementation. Methods Patients (47 pre and 54 post) undergoing lung transplantation were identified from institutional database from January 2016 to October 2019. Detailed chart review and analysis of institutional cost data was performed. Univariate analysis was performed to compare eras. Results Similar short-term mortality and primary graft dysfunction were observed between groups. Decreased local donation (68% vs 6%, p < 0.001), increased travel distance (145 vs 235 miles, p = 0.004), travel cost ($8,626 vs $14,482, p < 0.001), and total procurement cost ($60,852 vs. $69,052, p = 0.001) were observed post implementation. We also document an increase in waitlist mortality post-implementation (6.9 vs 31.6 per 100 patient years, p < 0.001). Conclusions Following implementation of the new allocation policy in a small to medium size center, several changes were in accordance with policy intention. However, concerning shifts emerged including increased waitlist mortality and resource utilization. Continued close monitoring of transplant centers stratified by size and location are paramount to maintaining global availability of lung transplantation to all Americans regardless of geographic residence or socioeconomic status. (Word Count: 219/250)

Innate immune pathways early after pulmonary transplantation have been shown to cause primary graft dysfunction (PGD) and also predispose to late graft failure. Recent studies in animal models have elucidated critical mechanisms governing such innate immune responses. Here, we discuss pathways of inflammatory cell death, triggers for sterile and infectious inflammation, and signaling cascades that mediate lung injury early after transplantation. These studies highlight potential avenues for lung-specific therapies early following lung transplantation to dampen innate immune responses and improve outcomes.

Postpneumonectomy bronchopleural fistula with empyema is a rare complication with devastating consequences that can occur at any time after pneumonectomy. Over the years multiple methods have been developed to treat this morbid condition. The most frequently utilized procedure to manage a bronchopleural fistula is a repeat thoracotomy with fistula repair and muscular flap coverage. However, this necessitates operating in densely fibrotic tissue planes, does not allow thorough dissection of the fistula, and has a high rate of recurrence. A less utilized technique, the transsternal transpericardial approach, allows the surgeon not only to enter the chest anteriorly and dissect in fresh tissue planes but also affords excellent exposure of the carina and fistula. This is an important approach with which all thoracic surgeons should be familiar as it offers an excellent option for large and recalcitrant postpneumonectomy bronchopleural fistulas.

OBJECTIVES The American Association for Thoracic Surgery, through its annual meeting, pilot grant funding, Scientific Affairs and Government Relations Committee activity, and academic development programs (Grant Writing Workshop, Clinical Trials Course, Innovation Summit), has aimed to develop the research careers of cardiothoracic surgeons. We hypothesized that American Association for Thoracic Surgery activities have helped increase National Institutes of Health grants awarded to cardiothoracic surgeons. METHODS A database of 1869 academic cardiothoracic surgeons in the United States was created in December 2020. National Institutes of Health grant records from 1985 to 2020 were obtained for each surgeon using National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results. Analyses were normalized to the number of active surgeons per year, based on the year of each surgeon's earliest research publication on Scopus. RESULTS A total of 346 cardiothoracic surgeons have received 696 National Institutes of Health grants totaling more than $1.5 billion in funding, with 48 surgeons actively serving as principal investigator of 66 R01 grants in 2020. The prevalence of research grants (7.4 vs 5.6 grants per 100 active surgeons, P

Background Complex cryptoglandular fistulas (CCF) arise from infected anal glands and are often associated with substantial morbidity and healthcare utilization. Standarized patient-reported outcome measures (PROMs) for CCF are lacking. Thus, we aimed to develop a disease-specific PROM to assess the burden of symptoms and their impact on daily life in patients with CCF. Methods To develop a conceptual model, a targeted literature review was conducted to identify symptoms and impacts on daily life associated with CCF. Existing PROMs relating to anal fistulas were also sought. Semi-structured interviews with colorectal surgeons (n=5) assessed clinical perspectives on patient experience of CCF. A draft item pool was developed based on the refined conceptual model and using the Quality of Life in Patients with Anal Fistula Questionnaire as a reference. The tool was refined through concept elicitation interviews on the symptoms and impacts of CCF, and cognitive debriefing on the interpretation, understanding and response to each item. Interviews were conducted until concept saturation was achieved and patient feedback suggested no further refinements were required. Results The literature review identified discharge, pain, faecal incontinence and bleeding as the most prevalent symptoms, and embarrassment as the most prevalent impact on daily life. Results from surgeon interviews were then used to revise the initial conceptual model. Twenty US adults (60% female; mean age, 49 years) with clinically confirmed CCF participated in interviews (four waves of n=5). Patients identified 10 salient symptoms and 11 salient impacts on daily life (salient defined as mention by ≥50% of patients and mean disturbance rating ≥5 on a 10-point scale). The final conceptual model included the main symptoms and treatment-related effects, and impacts on daily life. The draft item pool was refined, resulting in a final PROM consisting of 14 items (covering frequency and severity) relating to symptom domains – discharge, incontinence, pain, irritation, odour, abscess – and 6 items relating to health-related quality of life domains – functional, physical, psychological, social health. The PROM features a 7-day recall period, with responses mostly given on a 5-point verbal rating scale. Cognitive debriefing confirmed that the PROM was clear, easy to understand and relevant to patients’ experiences. Conclusion The 20-item CCF questionnaire (CCFQ-20) is a new PROM that has been developed and tested for content validity, following expert guidance and regulatory best practices. It addresses a comprehensive set of salient symptoms and impacts experienced by patients with CCF. Psychometric testing is required to fully evaluate this PROM. Sponsor: Takeda Pharmaceuticals USA, Inc.

Purpose Multiple immunologic and physiologic insults can contribute to chronic lung allograft dysfunction (CLAD). Thy-1 is a surface glycoprotein that can downregulate fibroblast differentiation to myofibroblasts and fibroblast activation. The role of Thy-1 in CLAD has not been explored. Methods We utilized the minor antigen mismatched C57BL/6 (B6)→C57BL/10 (B10) model of murine lung transplantation. To mimic bacterial infection some mice received LPS (5μg in 50μl PBS/dose) intratracheally every 4 days until sacrifice on postoperative day 30 while some mice were treated with saline. We transplanted either wild type B6 or Thy-1 deficient grafts to B10 recipient mice (B6wt→B10 vs. B6Thy1-/−→B10). Grafts were assessed based on histological grading for obliterative bronchiolitis (OB) and parenchymal fibrosis. To assess the role of LPS on fibroblast-specific Thy-1 expression, we utilized primary cell cultures of murine lung fibroblasts isolated from B6 mice, using media containing 1μg/ml of LPS. Results LPS treatment resulted in CLAD which was more severe in B6Thy1-/- donors(Figure A).More importantly immunohistochemical evaluation demonstrated that that all OB and fibrotic lesion, even in wild-type donors consisted of Thy-1 negative fibroblast. In vitro administration of LPS significantly downregulated Thy-1 in wild-type fibroblast through the downregulation of protein-specific mRNA (P Conclusion We for the first time demonstrate the link between the downregulation of Thy-1 and CLAD. We also demonstrate that LPS results in loss of Thy-1 on stromal cells thus contributing to proliferative airway lesions and parenchymal fibrosis. Our findings suggest that Thy-1 replacement may serve as a therapeutic option to prevent chronic rejection.

Objective Severe postesophagectomy gastric conduit dysfunction refractory to standard endoscopic intervention is rare, with few published reports discussing timing, technique, or results of reoperation. This case series examines assessment and management of severe conduit dysfunction and details techniques for conduit revision. Methods We retrospectively reviewed patients who underwent esophagectomy between September 2008 and October 2015 and studied patients who underwent conduit revision. Results More than 400 patients underwent Ivor Lewis or transhiatal esophagectomies during this 7-year period. Eight patients underwent reoperation for conduit revision. The strategy for initial anastomosis and management of the pylorus were variable. Symptoms included dysphagia, delayed emptying, aspiration, and weight loss. Evaluation and management included esophagram, computed tomography, repeated esophagoscopy with pyloric intervention, and selective anastomotic dilation. Two patients also had associated paraconduit hiatal hernias. Average time to reoperation was 3.8 years (range 2 weeks to 6.5 years). All revisions were performed through a thoracotomy with either laparoscopy or laparotomy. Revisions were completed in 7 patients. Average length of stay was 9.9 days (range 4-21). Average follow up was 10.1 months (range 1-36). The completed revisions led to restoration of a regular diet with improved patient satisfaction. Conclusions Severe gastric conduit dysfunction after esophagectomy is rare. Symptoms, esophagram findings, and response to interventional esophagoscopy guide the decision to revise the conduit. Principles of conduit revision include reducing paraconduit hernias, reducing redundant conduit, tubularizing a dilated conduit, and ensuring adequate gastric drainage. Selective revision was performed with minimal morbidity and durable improvement in subjective symptoms of dysphagia and reflux.

Background Delayed chest closure is an increasingly used approach in the management of bleeding and hemodynamic instability after lung transplantation. We sought to evaluate the impact of delayed chest closure on surgical site infection. Methods We performed a single-center retrospective cohort study and included adult patients who received a lung transplant at our center between January 1, 2010, and July 31, 2014. We defined surgical site infection as a thoracotomy incision wound or pleural space infection. Follow-up was complete through 6 months after transplantation. We used logistic regression models to examine the impact of delayed chest closure on surgical site infection and to identify other potential risk factors. Results During the study period, 67 of the 232 transplant procedures (29%) required delayed chest closure, and surgical site infection developed in 22 recipients (9%). Among the patients with surgical site infection, 18 experienced a wound infection, and 8 experienced a pleural space infection; 4 experienced concomitant wound and pleural space infection. Among the 67 who underwent delayed chest closure, 13 patients (19%) experienced a surgical site infection compared with 9 of the 165 patients (5%) who underwent primary closure ( p = 0.001). In multivariate analysis, delayed chest closure was an independent risk factor for surgical site infection. Conclusions Although delayed chest closure may have an important role in the immediate management of recipients of a lung transplant, it is an independent risk factor for surgical site infection, and this is associated with increased morbidity.

BACKGROUND Currently, there are no clinically approved treatments for ischemia-reperfusion injury after lung transplantation. Pre-clinical animal models have demonstrated a promising efficacy of adenosine 2A receptor (A2AR) agonists as a treatment option for reducing ischemia-reperfusion injury. The purpose of this human study, is to conduct a Phase I clinical trial for evaluating the safety of continuous infusion of an A2AR agonist in lung transplant recipients. METHODS An adaptive, two-stage continual reassessment trial was designed to evaluate the safety of regadenoson (A2AR agonist) in the setting of lung transplantation. Continuous infusion of regadenoson was administered to lung transplant recipients that was started at the time of skin incision. Adverse events and dose-limiting toxicities, as pre-determined by a study team and assessed by a clinical team and an independent safety monitor, were the primary end-points for safety in this trial. RESULTS Between January 2018 and March 2019, 14 recipients were enrolled in the trial. Of these, 10 received the maximum infused dose of 1.44 µg/kg/min for 12 hours. No dose-limiting toxicities were observed. The steady-state plasma regadenoson levels sampled before the reperfusion of the first lung were 0.98 ± 0.46 ng/ml. There were no mortalities within 30 days. CONCLUSIONS Regadenoson, an A2AR agonist, can be safely infused in the setting of lung transplantation with no dose-limiting toxicities or drug-related mortality. Although not powered for the evaluation of secondary end-points, the results of this trial and the outcome of pre-clinical studies warrant further investigation with a Phase II randomized controlled trial.

Pain after thoracic surgery remains the Achilles heel of our discipline. Many techniques have been developed over the years to address postoperative pain to varying degrees of success. It is with this in mind that we reviewed the study by Raveglia et al . (1) with great interest. The authors present a single-institution prospective randomized trial comparing use of a wound protector to the standard rigid trocar for the camera port during video-assisted thoracic surgery (VATS) lung resections. This novel technique was first published by the authors in 2016 (2) and is now common practice at their institution. The main study outcome was postoperative pain measured by both visual analog scale as well as morphine consumption.

Background With the growing number of treatment options for metastatic breast cancer, patient (pt) perspective on treatment and treatment satisfaction is increasingly important to assess. A literature search was conducted to identify commonly utilized measures of pt preference. The Treatment Satisfaction Questionnaire for Medication (TSQM) was identified as the most comprehensive measure to assess patient-reported treatment effectiveness, side effects, convenience, and overall satisfaction with medication for a wide variety of medical conditions. The broad nature of the TSQM allows for assessment of treatment satisfaction across indications; however it has not been evaluated for specific use in populations of cancer patients. We assessed the content validity of the TSQM v1.4® with previously treated breast cancer (BC) patients to determine if any modifications were necessary to ensure relevance in this population. Methods This non-interventional, cross-sectional qualitative study used individual semi-structured cognitive interviews to: (1) assess content of the TSQM and relevance for BC, and (2) identify necessary modifications as based on patient interviews. 15 BC pts with a mix of receptor types [hormone receptor positive (HR+), HER2+, triple negative (TNBC)], age > 18 yrs and currently receiving or recently completed first-, second-, or third-line therapy for Stage IIIA to IV were included to ensure applicability across BC. Pts meeting inclusion/exclusion criteria were identified through database review and recruited. Interviews were conducted in three waves of five pts and necessary modifications were made to the TSQM after each wave. Interviews were audio recorded and transcribed. Results Mean age of participants was 53 years; 6 patients were HR+/HER2+, 2 patients were HR+/HER2-, 2 patients were HR-/HER2+, 5 patients were TNBC. Pts reported that the three items comprising the effectiveness scale were not relevant in BC and are difficult to answer. Specifically, pts felt the first item ('ability of medication to treat/prevent condition') would be highly dependent on scan results, and indicated that the term 'prevent' is not relevant to the experience of BC pts with a metastatic diagnosis. With the second item ('relieves symptoms'), most pts reported that they did not experience symptoms related to their cancer and thus were unsure how to respond. Pts were confused by the term 'symptoms' and interpreted it as 'side effects from treatment' rather than disease-related. For the third item ('time it takes medication to start working'), pts noted the only way to definitively know if a cancer medication has started working is with scan results, and they would not be able to assess this. Pts found the remaining TSQM items to be relevant, clear, and easy to understand, and offered a few suggestions for improvement that can be evaluated in future research. Conclusion BC pts did not find the TSQM effectiveness scale items relevant to the assessment of their treatment experience, and as a result these items were eliminated in the modified TSQM for Breast Cancer (TSQM-BC). The TSQM-BC is content valid for use in breast cancer studies. Psychometric performance of this version of the TSQM-BC will be evaluated in future research. Citation Format: DeBusk KPA, Maddux LM, Turner-Bowker DM, Krupnick RN, Skolas KL, Patel SL, Petersen JA. Content validation and modification of the treatment satisfaction questionnaire for medication (TSQM) for breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-14.

Background The value of adjuvant chemotherapy for patients with positive lymph nodes (+LNs) after induction therapy and resection of esophageal cancer is controversial. This study assesses survival benefit of adjuvant chemotherapy in this cohort. Methods We analyzed our single-institution database for patients with +LNs after induction therapy and resection of primary esophageal cancer between 2000 and 2013. Factors associated with survival were analyzed using a Cox proportional hazards model. Results A total of 101 of 764 esophagectomy patients received induction and had +LNs on final pathologic examination. Forty-five also received adjuvant therapy: 37 of 45 (82%) received chemotherapy alone, 1 of 45 (2%) received radiation alone, and 7 of 45 (16%) received both. Pathologic stage was IIB in 21 (47%), IIIA in 19 (42%), and IIIB in 5 (11%). In 56 node-positive patients with induction but not adjuvant therapy, pathologic stage was IIB in 28 (50%), IIIA in 18 (32%), IIIB in 7 (13%), and IIIC in 3 (5%). Neither age nor comorbidity score differed between cohorts. Adjuvant patients experienced a shorter hospital length of stay (mean, 10 days [range, 6 to 33 days] versus 11 days [range, 7 to 67 days]; p = 0.03]. Median survival favored the adjuvant group: 24.0 months (95% confidence interval, 16.6 to 32.2 months) versus 18.0 months (95% confidence interval, 11.1 to 25.0 months); p = 0.033). Multivariate Cox regression identified adjuvant therapy, length of stay, and number of +LNs as influential for survival. Conclusions Optimal management of node-positive patients after induction therapy and esophagectomy remains unclear, but in this series, adjuvant therapy, length of stay, and number of +LNs impacted survival. A prospective trial may reduce potential bias and guide the evaluation of adjuvant therapy in this patient population.

A substantial proportion of patients with clinical stage I non-small cell lung cancer (NSCLC) have more advanced disease on final pathologic review. We studied potentially modifiable factors that may predict pathologic upstaging.Data of patients with clinical stage I NSCLC undergoing resection were obtained from the National Cancer Database. Univariate and multivariate analyses were performed to identify variables that predict upstaging.From 1998 to 2010, 55,653 patients with clinical stage I NSCLC underwent resection; of these, 9,530 (17%) had more advanced disease on final pathologic review. Of the 9,530 upstaged patients, 27% had T3 or T4 tumors, 74% had positive lymph nodes (n0), and 4% were found to have metastatic disease (M1). Patients with larger tumors (38 mm vs 29 mm, p0.001) and a delay greater than 8 weeks from diagnosis to resection were more likely to be upstaged. Upstaged patients also had more lymph nodes examined (10.9 vs 8.2, p0.001) and were more likely to have positive resection margins (10% vs 2%, p0.001). Median survival was lower in upstaged patients (39 months vs 73 months). Predictors of upstaging in multivariate regression analysis included larger tumor size, delay in resection greater 8 weeks, positive resection margins, and number of lymph nodes examined. There was a linear relationship between the number of lymph nodes examined and the odds of upstaging (1 to 3 nodes, odds ratio [OR] 2.01;18 nodes OR 6.14).Pathologic upstaging is a common finding with implications for treatment and outcomes in clinical stage I NSCLC. A thorough analysis of regional lymph nodes is critical to identify patients with more advanced disease.

Introduction The relative roles of surgery and stereotactic body radiation therapy in stage I non–small-cell lung cancer (NSCLC) are evolving particularly for marginally operable patients. Because there is limited prospective comparative data for these treatment modalities, we evaluated their relative use and outcomes at the population level using a national database. Methods Patient variables and treatment-related outcomes were abstracted for patients with clinical stage I NSCLC from the National Cancer Database. Patients receiving surgery were compared with those undergoing stereotactic body radiation therapy (SBRT) in exploratory unmatched and subsequent propensity matched analyses. Results Between 1998 and 2010, 117,618 patients underwent surgery or SBRT for clinical stage I NSCLC. Of these, 111,731 (95%) received surgery, whereas 5887 (5%) underwent SBRT. Patients in the surgery group were younger, more likely to be males, and had higher Charlson comorbidity scores. SBRT patients were more likely to have T1 (versus T2) tumors and receive treatment at academic centers. Thirty-day surgical mortality was 2596 of 109,485 (2.4%). Median overall survival favored the surgery group in both unmatched (68.4 versus 33.3 months, p p Conclusion In a propensity matched comparison, patients selected for surgery have improved survival compared with SBRT. In the absence of information on cause of death and with limited variables to characterize comorbidity, it is not possible to assess the relative contribution of patient selection or better cancer control toward the improved survival. Rigorous prospective studies are needed to optimize patient selection for SBRT in the high-risk surgical population.

Background This study evaluated the cost-effectiveness of combination chemotherapy, radiotherapy, and surgical intervention (CRS) vs definitive chemotherapy and radiotherapy (CR) in clinical stage IIIA non-small cell lung cancer (NSCLC) patients at academic and nonacademic centers. Methods Patients with clinical stage IIIA NSCLC receiving CR or CRS from 1998 to 2010 were identified in the National Cancer Data Base. Propensity score matching on patient, tumor, and treatment characteristics was performed. Medicare allowable charges were used for treatment costs. The incremental cost-effectiveness ratio (ICER) was based on probabilistic 5-year survival and calculated as cost per life-year gained. Results We identified 5,265 CR and CRS matched patient pairs. Surgical resection imparted an increased effectiveness of 0.83 life-years, with an ICER of $17,618. Among nonacademic centers, 1,634 matched CR and CRS patients demonstrated a benefit with surgical resection of 0.86 life-years gained, for an ICER of $17,124. At academic centers, 3,201 matched CR and CRS patients had increased survival of 0.81 life-years with surgical resection, for an ICER of $18,144. Finally, 3,713 CRS patients were matched between academic and nonacademic centers. Academic center surgical patients had an increased effectiveness of 1.5 months gained and dominated the model with lower surgical cost estimates associated with lower 30-day mortality rates. Conclusions In stage IIIA NSCLC, the selective addition of surgical resection to CR is cost-effective compared with definitive chemoradiation therapy at nonacademic and academic centers. These conclusions are valid over a range of clinically meaningful variations in cost and treatment outcomes.

Purpose Our aim was to determine the association between the development of post-transplant neutropenia and subsequent antibody-mediated rejection (AMR) in a population of adult lung transplant recipients. Methods We performed a single center retrospective cohort study of adult lung transplant recipients between 2008 and 2013. Neutropenia was defined as an absolute neutrophil count (ANC) Results The cohort included 228 lung transplant recipients, 101 (42.1%) of whom developed neutropenia. Of those patients who developed neutropenia, 42 had mild neutropenia, 34 had moderate neutropenia and 25 had severe neutropenia. Patients with Neutropenia had a significant increased risk of subsequent AMR (OR 3.16, 95% CI 1.37-7.28, p=0.005). Additionally, patients who developed neutropenia had decreased AMR-free survival (HR for death 2.90, 95% CI 1.32-6.37, p=0.008). This relationship appeared to correlate with degree of neutropenia. Patients with severe moderate and severe neutropenia had lower AMR-free survival than patients with mild or no neutropenia. Conclusion The development of neutropenia is associated with an increased risk of subsequent AMR in lung transplant recipients. Further investigation into the underlying mechanism of this association is warranted.

Background Lung transplantation outcomes are heavily scrutinized, given the high stakes of these operations, yet the Center for Medicare and Medicaid Services (CMS) method of using Scientific Registry of Transplant Recipients (SRTR) risk-adjusted outcomes to identify underperforming centers is controversial. We hypothesized that CMS flagging results in conservative behavior for recipient and organ selection, resulting in fewer patients added to the waitlist and fewer transplantations performed. Methods SRTR reports from July 2012 through July 2017 were included. Center characteristics were compared, stratified by number of flagging events. The impact of flagging for underperformance on risk aversion outcomes was analyzed using a mixed-effects regression model. Results A total of 72 centers had reported SRTR data during the study period. Of these, 21 centers (29%) met flagging criteria a median of 2 times (interquartile range, 1 to 4 times) for a total of 53 events. Flagging had no statistically significant impact on waitlist or transplantation volume and patient selection by mixed-effects modeling. Despite similar average expected 1-year survival (86.6% versus 87.7%, p = 0.27), centers that were flagged only once added more patients per year to the waitlist (16.3 patients versus 7.8 patients, p = 0.01) and performed more transplantations per year (28.4 transplantations versus 11.1 transplantations, p = 0.01). Conclusions This analysis defines center-level trends in lung transplantation after CMS flagging. Contrary to our primary hypothesis, flagging did not result in temporal center-level changes. However, programs on prolonged probation demonstrated reduced activity, which likely indicates a shift to higher performing centers.

Purpose Despite the growing experience in lung transplantation a significant number of patients rapidly succumb to chronic rejection in the form of bronchiolitis obliterans (OB). The reasons for such discrepancies are unknown but have been suspected to relate to individual variability in gut and lung microbiome. Methods To study the role of the microbiome in controlling lung immunology we transplanted C57BL/10 lungs to C57BL/6 recipients from either Jackson Lab, Maine or Envigo facilities in Maryland vs Indiana. Histological grading of acute and chronic rejection, in the form of OB was performed on days 7 and 21 respectively with flow cytometric analysis of the lungs in parallel. Results Recipients from the Maine facility rapidly rejected lung grafts with high ISHLT rejection grades (2.8±0.37) by day 7 while Maryland recipients were rejection-free (0.25±0.25). Delayed histologic evaluation on day 21 post-engraftment revealed evidence of OB in 40% of Indiana recipients while 0% in Maine or Maryland mice(Fig.1A). Flow cytometric analysis revealed a high prevalence of CD4+Foxp3+ Tregs in Maryland recipients (29.56±2.32%) but lower in Maine and Indiana mice while T cell IL-17 levels were also different between them. Systemic different TGF-β levels were also observed. Treatment of Maryland recipients with broad-spectrum antibiotics affected TGF-β levels, decreased the Treg proportion (14.24±1.47%, p Conclusion Our data demonstrate that mice from different origins mount different lung allograft-specific microbiome-related immune responses. Furthermore it suggests that microbiome-dependent TGF beta levels may contribute to the generation of protective Tregs and ameliorate both acute and chronic rejection. Such data puts into question the notion that TGF-β contributes to lung fibrosis and opens up therapeutic avenues of microbiome manipulation to augment the TGF-β -Treg axis.

BACKGROUND: The association of body mass index (BMI) with survival after lung transplantation remains controversial, owing to conflicting evidence in the literature. Previous reports have used traditional BMI categories, included patients who underwent transplantation before implementation of the lung allocation score (LAS), or were limited by single-center experiences. Here we evaluated the association of individual BMI units with short-term and long-term mortality in a large national database following implementation of the LAS. METHODS: The Scientific Registry of Transplant Recipients database was used to collect data for 17,233 adult lung transplantations performed between May 2005 and June 2016. The primary outcome was all-cause mortality at 90 days and 1 year posttransplantation. Logistic regression modeling was used to independently predict mortality per BMI unit, adjusting for donor and recipient factors. RESULTS: BMI was an independent predictor of mortality at both 90 days and 1 year. At 90 days, a BMI of 25 was associated with the lowest predicted probability of death (0.053; 95% confidence interval [CI], 0.047-0.049), with increased odds of mortality at BMI ≤20 and ≥28. At 1 year, a BMI of 26 was associated with the lowest predicted probability of death (0.12; 95% CI, 0.110.13), with increased odds of mortality at BMI ≤24 and ≥28. CONCLUSIONS: Each individual BMI unit has a quantifiable effect on posttransplantation survival, and the patterns of effect do not fit into the predefined BMI categories. The mortality risk associated with BMI should be considered by transplant centers when making listing decisions and by regulatory bodies for estimating expected outcomes. (J Thorac Cardiovasc Surg 2018;155:1871-9)

Improved survival of patients with early-stage non-small cell lung cancer (NSCLC) undergoing resection at high-volume centers has been reported. However, the effect of institution is unclear in stage IIIA NSCLC, where a variety of neoadjuvant and adjuvant therapies are used.Treatment and outcomes data of clinical stage IIIA NSCLC patients undergoing resection as part of multimodality therapy was obtained from the National Cancer Database. Multivariable regression models were fitted to evaluate variables influencing 30-day mortality and overall survival.From 1998 to 2010, 11,492 clinical stage IIIA patients underwent resection at community centers, and 7,743 patients received resection at academic centers. Academic center patients were more likely to be younger, female, non-Caucasian, have a lower Charlson-Deyo comorbidity score, and to receive neoadjuvant chemotherapy (49.6% vs 40.6%; all p0.001). Higher 30-day mortality was associated with increasing age, male gender, preoperative radiotherapy, and pneumonectomy. Patients undergoing operations at academic centers experienced lower 30-day mortality (3.3% vs 4.5%; odds ratio, 0.75; 95% confidence interval [CI], 0.60 to 0.93; p0.001). Decreased long-term survival was associated with increasing age, male gender, higher Charlson-Deyo comorbidity score, and larger tumors. Neoadjuvant chemotherapy (hazard ratio, 0.66; 95% CI, 0.62 to 0.70), surgical intervention at an academic center (hazard ratio, 0.92; 95% CI, 0.88 to 0.97), and lobectomy (hazard ratio, 0.72; 95% CI, 0.67 to 0.77) were associated with improved overall survival.Stage IIIA NSCLC patients undergoing resection at academic centers had lower 30-day mortality and increased overall survival compared with patients treated at community centers, possibly due to higher patient volume and an increased rate of neoadjuvant chemotherapy.

Conflicting evidence currently exists regarding the causes and effects of delay of care in non-small cell lung cancer (NSCLC). We hypothesized that delayed surgery in early-stage NSCLC is associated with worse short-term and long-term outcomes.Treatment data of clinical stage I NSCLC patients undergoing surgical resection were obtained from the National Cancer Data Base (NCDB). Treatment delay was defined as resection 8 weeks or more after diagnosis. Propensity score matching for patient and tumor characteristics was performed to create comparable groups of patients receiving early (less than 8 weeks from diagnosis) and delayed surgery. Multivariable regression models were fitted to evaluate variables influencing delay of surgery.From 1998 to 2010, 39,995 patients with clinical stage I NSCLC received early surgery, while 15,658 patients received delayed surgery. Of these, 27,022 propensity-matched patients were identified. Those with a delay in care were more likely to be pathologically upstaged (18.3% stage 2 or higher versus 16.6%, p0.001), have an increased 30-day mortality (2.9% vs 2.4%, p = 0.01), and have decreased median survival (57.7 ± 1.0 months versus 69.2 ± 1.3 months, p0.001). Delay in surgery was associated with increasing age, non-white race, treatment at an academic center, urban location, income less than $35,000, and increasing Charlson comorbidity score (p0.0001 for all). Delayed patients were more likely to receive a sublobar resection (17.2% vs 13.1%, p0.001).Patients receiving delayed resection for clinical stage I NSCLC have higher comorbidity scores that may affect ability to perform lobectomy and result in higher perioperative mortality. However, delay in resection is independently associated with increased rates of upstaging and decreased median survival. Strategies to minimize delay while medically optimizing higher risk patients are needed.

To minimize the stress of operations, improve the patient experience, reduce variability, and optimize resource utilization, we implemented a thoracic enhanced recovery after surgery (ERAS) protocol and evaluated progress after 1 year.Two protocols were developed: video-assisted thoracic surgery (ERAS-VATS) and thoracotomy (ERAS-T). Each incorporated preoperative patient education, carbohydrate loading, opioid-sparing analgesia, conservative fluid management, and early ambulation. Patient outcomes, length of stay, pain scores, opioid use, fluid administration, and cost for ERAS patients were compared with historic controls from the year before program initiation.Historic VATS (n = 162) were compared with 81 ERAS-VATS patients. Median postoperative morphine equivalents (86 versus 22 mg, p0.0001), total fluid balance (1279 versus 227 mL, p0.0001), and mean inflation adjusted hospital costs ($20,169 versus $14,870, p = 0.0003) all decreased significantly. Historic thoracotomy patients (n = 62) were compared with 58 ERAS-T patients. Median postoperative morphine equivalents (130 versus 54 mg, p 0.0001), total fluid balance (788 versus -489 mL, p = 0.012), length of stay (6.0 versus 4.0 days, p = 0.009), and mean inflation adjusted hospital costs ($41,950 versus $26,089, p0.00001) all decreased significantly.Implementation of thoracic ERAS is a dynamic process with potential to improve outcomes in thoracic surgical procedures. In the first year we shortened length of stay, decreased opioid usage, minimized fluid overload, and decreased hospital costs.

Background Controversy remains regarding the role of pyloric drainage procedures after esophagectomy with gastric conduit reconstruction. We aimed to compare the effect of pyloric drainage strategies upon subsequent risk of complications suggestive of conduit distention, including aspiration and anastomotic leak. Methods A retrospective study was conducted reviewing patients undergoing esophagectomy between January 2007 and April 2012. Prospectively collected data included baseline comorbidities, operative details, hospital course, and complications. Statistical comparisons were performed using analysis of variance for continuous variables and χ 2 testing for categorical variables. Results There were 361 esophagectomies performed during the study period; 68 were excluded from analysis (for prior esophagogastric surgery or benign disease or both). Among 293 esophagectomies included, emptying procedures were performed as follows: 44 (15%), no drainage procedure; 197 (67%), pyloromyotomy/pyloroplasty; 8 (3%), dilation alone; 44 (15%), dilation plus onabotulinumtoxinA. Aspiration occurred more frequently when no pyloric intervention was performed (5 of 44 [11.4%] versus 6 of 249 [2.4%], p = 0.030). The incidences of anastomotic leak (18 [6.1%]) and gastric outlet obstruction (5 [1.7%]) were statistically similar among groups. Subgroup analysis demonstrated persistence of these findings when limiting the comparison to transthoracic esophagectomies. Major complications directly related to pyloroplasty/pyloromyotomy occurred in 2 patients (0.6%), including 1 death (0.3%). Conclusions These data suggest that omission of pyloric intervention at the index operation results in more frequent aspiration events. The combination of dilation plus onabotulinumtoxinA provided for a similar complication profile compared with surgical drainage. Future prospective comparisons are needed to evaluate these short-term effects of pyloric intervention as well as long-term sequelae such as dumping syndrome and bile reflux.

Introduction:The role of surgery in addition to chemotherapy and radiation for stage IIIA non–small-cell lung cancer (NSCLC) remains controversial. Because there are limited data on the benefit from surgery in this setting, we evaluated the use of combined modality therapy nationally and explored the outcomes with and without the addition of surgery.Methods:Patient variables and treatment-related outcomes were abstracted for patients with clinical stage IIIA NSCLC from the National Cancer Database. Patients receiving chemotherapy and radiation were compared with those undergoing chemotherapy, radiation, and surgery (CRS) in any sequence.Results:Between 1998 and 2010, 61,339 patients underwent combined modality treatment for clinical stage IIIA NSCLC. Of these, 51,979 (84.7%) received chemotherapy and radiation while 9360 (15.3%) underwent CRS. Patients in the CRS group were younger, more likely female patients and Caucasians, and had smaller tumors and lower Charlson comorbidity scores. The 30-day surgical mortality was 200 of 8993 (2.2%). The median overall survival favored the CRS group in both unmatched (32.4 months versus 15.7 months, p < 0.001) and matched analysis based on patient characteristics (34.3 versus 18.4 months, p < 0.001).Conclusions:There is significant heterogeneity in the treatment of stage IIIA NSCLC in the United States. Patients selected for surgery in addition to chemoradiation therapy seem to have better long-term survival.

The American College of Surgery Oncology Group (ACOSOG) trials z4032 and z4033 prospectively characterized lung cancer patients as "high-risk" for surgical intervention, and these results have appeared frequently in the literature. We hypothesized that many patients who meet the objective enrollment criteria for these trials ("high-risk") have similar perioperative outcomes as "normal-risk" patients.We reviewed a prospective institutional database and classified patients undergoing resection for clinical stage I lung cancer as "high-risk" and "normal-risk" by ACOSOG major criteria.From 2000 to 2010, 1,066 patients underwent resection for clinical stage I lung cancer. Of these, 194 (18%) met ACOSOG major criteria for risk (preoperative forced expiratory volume in 1 second or diffusion capacity of the lung for carbon monoxide≤50% predicted). "High-risk" patients were older (66.4 vs 64.6 years, p=0.02) but similar to controls in sex, prevalence of hypertension, diabetes, and coronary artery disease. "High-risk" patients were less likely than "normal-risk" patients to undergo a lobectomy (117 of 194 [60%] vs 665 of 872 [76%], p0.001). "High-risk" and control patients experienced similar morbidity (any complication: 55 of 194 [28%] vs 230 of 872 [26%], p=0.59) and 30-day mortality (2 of 194 [1%] vs 14 of 872 [ 2%], p=0.75). A regression analysis showed age (hazard risk, 1.04; 95% confidence interval, 1.02 to 1.06) and coronary artery disease (hazard risk, 1.58; 95% confidence interval, 1.05 to 2.40) were associated with an elevated risk of complications in those undergoing lobectomy, whereas female sex (hazard ratio, 0.63; 95% confidence interval, 0.44 to 0.91) was protective. ACOSOG "high-risk" status was not associated with perioperative morbidity.There are no important differences in early postsurgical outcomes between lung cancer patients characterized as "high-risk" and "normal-risk" by ACOSOG trial enrollment criteria, despite a significant proportion of "high-risk" patients undergoing lobectomy.

Purpose Intragraft tertiary lymphoid organs (TLOs) are generally associated with the generation of deleterious immune responses. In contrast, we have shown that Foxp3+ cells residing within bronchus-associated lymphoid tissue (BALT), a pulmonary TLO, are required for maintenance of allograft tolerance. Here, we set out to define the cellular and molecular mechanisms that mediate the induction of BALT in tolerant lung allografts. Methods Balb/c lungs were transplanted into B6 wild-type (WT), RORγt-Cre AHR flox (Group 3 innate lymphoid cells (ILC3)-deficient), TCRδ−/− (γδ T cell-deficient), anti-IL23 antibody-treated mice and IL-22 KO mice (n≥4/group). Recipients received anti-CD40L (day 0) and CTLA4-Ig (day 2) to induce tolerance. 7 or 30 days after transplantation grafts were evaluated by histology, flow cytometry and RT-PCR. Results 30 days after transplantation into WT hosts BALT was present in all lung allografts, characterized by expression of PNAd, a marker of high endothelial venules, and lymphoid follicles rich in B cells and Foxp3+ cells (Fig. 1). Graft expression of IL-22 and IL-23 (p Conclusion IL-22 regulates the formation of BALT within tolerant lungs through a process mediated by graft-infiltrating ILC3s and γδ T cells. This is in contrast to previous findings that induction of TLOs is dependent on lymphotoxin or IL-17 signaling. Thus, our findings have important implications for strategies to induce lung transplant tolerance.

Study Objective To determine whether patients receiving perioperative glycopyrrolate during midurethral sling surgery had more acute but temporary postoperative urinary retention. Design Retrospective cohort from 2006 to 2011. Setting Northern Virginia community urology practice. Measurements To minimize variability in surgical technique and postoperative care, all cases were from a single fellowship-trained urologist who performed most of the female incontinence procedures. Inclusion criteria were charts of women, 18 years of age or older, who had a primary preoperative diagnosis of stress urinary incontinence (SUI) and who underwent a midurethral sling procedure. Of 151 patients charts, 135 met study eligibility: 57 (42.2%) patients received glycopyrrolate; 78 (57.8%) did not. The postoperative course of those who did and did not receive glycopyrrolate was compared and formed the basis of group allocation. Data collected included age, body mass index, incontinence type, smoking status, diabetes mellitus, surgery performed, anesthesia type, estimated blood loss, intraoperative fluids, surgery end time to void, and postoperative urinary retention. Main Results No differences existed between the groups in baseline or surgical data. Seven patients (5.2%) had acute temporary postoperative retention, two of whom received glycopyrrolate and 5 did not (3.51% vs 6.41%; relative risk [RR] 0.55, 95% CI 0.11 -2.72, P = 0.70). Excluding those with continued persistent voiding dysfunction beyond 48 hours from surgery, only 3 patients (2.22%) had acute temporary postoperative urinary retention: one received glycopyrrolate and two did not (1.75% vs 2.56%; RR 0.68, 95% CI 0.064 - 7.36; P = 0.99). Conclusion Acute temporary postoperative urinary retention is rare after midurethral slings. Glycopyrrolate during anesthesia induction does not appear significantly to increase this rate.

Objective The need for esophageal lengthening (EL) as part of hiatal hernia (HH) repair is perceived to elevate perioperative risk and provide functionally inferior outcomes. Our objectives were to determine the risk factors of undergoing EL and to compare outcomes between operations with and without EL. We hypothesized that operative and functional outcomes for HH repair were similar in patients whether they required EL or not. Methods We reviewed institutional experience with EL as part of HH repair. The patients underwent symptom evaluation before and after surgery using a validated tool. Results Between 1999 and 2009, a total of 375 patients underwent HH repair. The operative approach was thoracotomy, 153 (41%); laparotomy, 18 (5%); laparoscopy, 167 (44%); or combined, 37 (10%). Of these, 168 (45%) required EL. There was a higher need for thoracotomy in the patients undergoing EL (79/168 vs 74/207, χ2 = 4.88, P = 0.034). The incidence of perioperative complications (leak, pneumonia, ileus, respiratory failure, and bleeding) was similar between the groups. Sixty-five selected patients undergoing EL were compared with 63 patients with comparable demographics not requiring EL. In a well-validated questionnaire that assessed symptoms before and after surgery, the patients undergoing EL showed significant improvement in their heartburn (76.8%), dysphagia (67.6%), regurgitation (71.7%), chest pain (91.9%), and nausea (86.5%) ( P < 0.05). The patients not undergoing EL also showed significant improvement in their heartburn (81.1%), dysphagia (71.1%), regurgitation (64.4%), chest pain (64.1%), and nausea (61.0%) ( P < 0.05). Improvement in symptoms, the continued use of antacid medications, and overall surgery satisfaction score were statistically similar between the two groups. Conclusions Operative and functional outcomes for HH repair with or without EL are acceptable and comparable. Thoracic surgeons should use EL without reservations for appropriate indications.

Background Past series have identified completion pneumonectomy (CP) as a high-risk operation. We evaluated factors affecting outcomes of CP with a selective approach to offering this operation. Methods We analyzed a prospective institutional database and abstracted information on patients undergoing pneumonectomy. Patients undergoing CP were compared with those undergoing primary pneumonectomy (PP). Results Between January 2000 and February 2011, 211 patients underwent pneumonectomy, of which 35 (17%) were CPs. Ten of 35 (29%) CPs were for benign disease and 25 of 35 (71%) for cancer. Major perioperative morbidity was seen in 21 of 35 (60%) with 4 (11%) perioperative deaths. In univariate analysis, postoperative bronchopleural fistula ( p = 0.05) and benign diagnosis ( p = 0.07) tended to be associated with perioperative mortality. All 10 patients undergoing CP for benign disease developed a major complication compared with 11 of 25 (44%) with malignancy, p = 0.002. A bronchopleural fistula (4 of 35, 11%) was more likely to occur in patients undergoing CP shortly after the primary operation (interval between lobectomy and CP; 0.28 vs 4.5 years; p = 0.018) with a trend toward a benign indication for operation ( p = 0.07). Median survival after CP for benign and malignant indications was 24.3 months and 36.5 months, respectively. Comparing CP patients to those undergoing PP (n = 176), CP patients were more likely to undergo an operation for benign disease (10 of 35, 29% vs 14 of 176, 8%, p = 0.001). Perioperative mortality for PP was 10 of 176 (5.7%), and was statistically similar to CP (11%). Conclusions Despite a selective approach, CP remains a morbid operation, particularly for benign indications. Rigorous preoperative optimization, ruling out contraindications to operation and attention to technical detail, are recommended.

Background National organizations have recommended quality measures for operations in early-stage non-small cell lung cancer (NSCLC). The outcomes of adherence to these guidelines are unknown. Methods Information about patients who underwent an operation for clinical stage I NSCLC was abstracted from the National Cancer Database. After reviewing current guidelines, the following quality measures were selected: anatomic resection, operation within 8 weeks of diagnosis, achievement of negative surgical margins, and sampling of 10 or more lymph nodes. Multivariate models identified variables independently associated with receiving quality measures and a Cox model created to evaluate overall survival. Results Between 2004 and 2013, 133,026 of 133,366 (99.7%), 126,598 of 133,366 (94.9%), 91,472 of 133,366 (68.6%), and 30,041 of 133,366 (22.5%) patients met one, two, three, or four measures. Income of at least $38,000/year (odds ratio [OR] 1.20, 95% CI: 1.15 to 1.24), insurance type (private insurance: OR 1.22, 95% CI: 1.09 to 1.36; Medicare: OR 1.16, 95% CI:1.04 to 1.30), centers with at least 38 cases/year (OR 1.18, 95% CI: 1.14 to 1.22), academic institutions (OR 1.31, 95% CI: 1.27 to 1.35), and clinical stage IB patients (OR 1.50, 95% CI: 1.40 to 1.60) were more likely to meet all four measures; whereas increasing age (OR 0.99, 95% CI: 0.99 to 0.99), women (OR 0.93, 95% CI: 0.91 to 0.96), non-Caucasian race (OR 0.83, 95% CI: 0.79 to 0.87), and increasing Charlson/Deyo comorbidity score (1: OR 0.90, 95% CI: 0.87 to 0.93; ≥2: OR 0.82, 95% CI: 0.79 to 0.86) were associated with lower likelihood. Pathologic upstaging (hazard ratio [HR] 1.84, 95% CI: 1.78 to 1.89) and meeting all four measures (HR 0.39, 95% CI: 0.31 to 0.48) were most powerfully associated with overall survival. Conclusions National adherence to quality measures in stage I NSCLC resection is suboptimal. Guideline compliance is strongly associated with survival, and vigorous efforts should be instituted by national societies to improve adherence.

Background The objectives of this study are to explore factors that are associated with use of adjuvant chemotherapy and to evaluate its impact on overall survival in node-negative patients who undergo lung and chest wall resection for non-small cell lung cancer (NSCLC). Methods Patients who underwent concomitant lung and chest wall resection for NSCLC were abstracted from the National Cancer Database. Clinical, pathologic, treatment, and follow-up data were obtained. Patients with pathologic nodal metastases or patients who received any radiation treatment were excluded, and the cohort was dichotomized based on administration of adjuvant postoperative chemotherapy. Results Between 1998 and 2010, 824 patients met the inclusion criteria. This cohort exclusively consisted of pT3 N0 patients who did not receive any induction treatment or adjuvant radiation treatment. Adjuvant chemotherapy was administered to 255 patients (31%). Patients in the chemotherapy group were younger and had shorter inpatient length of stay. Both groups had similar comorbidities, tumor size, unplanned readmission rate, and incomplete resection rate. In multivariable analysis, younger age and shorter length of stay were associated with a greater likelihood of receiving adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved survival (hazard ratio 0.74, 95% CI: 0.6 to 0.9), whereas increasing age, white race, length of inpatient stay, tumor size, and residual tumor were independently associated with greater risk of death. Conclusions Patients who undergo lobectomy with chest wall resection for locally advanced NSCLC should be strongly considered for postoperative adjuvant chemotherapy even in the absence of nodal disease. Actual selection of patients for adjuvant chemotherapy is affected by perioperative factors.

Background Induction therapy leads to significant improvement in survival for selected patients with stage IIIA non-small cell lung cancer. The ideal time interval between induction therapy and surgery remains unknown. Methods Clinical stage IIIA non-small cell lung cancer patients receiving induction therapy and surgery were identified in the National Cancer Database. Delayed surgery was defined as greater than or equal to 3 months after starting induction therapy. A logistic regression model identified variables associated with delayed surgery. Cox proportional hazards modeling and Kaplan-Meier analysis were performed to evaluate variables independently associated with overall survival. Results From 2006 to 2010, 1,529 of 2,380 (64.2%) received delayed surgery. Delayed surgery patients were older (61.2 ± 10.0 years versus 60.3 ± 9.2; p = 0.03), more likely to be non-white (12.4% versus 9.7%; p = 0.046), and less likely to have private insurance (50% versus 58.2%; p = 0.002). Delayed surgery patients were also more likely to have a sublobar resection (6.3% versus 2.9%). On multivariate analysis, age greater than 68 years (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.1 to 1.7) was associated with delayed surgery, whereas white race (OR, 0.75; 95% CI, 0.57 to 0.99) and private insurance status (OR, 0.82; 95% CI, 0.68 to 0.99) were associated with early surgery. Delayed surgery was associated with higher risk of long-term mortality (hazard ratio, 1.25; 95% CI, 1.07 to 1.47). Conclusions Delayed surgery after induction therapy for stage IIIA lung cancer is associated with shorter survival, and is influenced by both social and physiologic factors. Prospective work is needed to further characterize the relationship between patient comorbidities and functional status with receipt of timely surgery.

Background Patients with malignant pleural effusion (MPE) have varied expected survival and treatment options. We studied the relative cost-effectiveness of various interventions. Methods Decision analysis was used to compare repeated thoracentesis (RT), tunneled pleural catheter (TPC), bedside pleurodesis (BP), and thoracoscopic pleurodesis (TP). Outcomes and utility data were obtained from institutional data and review of literature. Medicare allowable charges were used to ensure uniformity. Base case analysis was performed for two scenarios: expected survival of 3 months and expected survival of 12 months. The incremental cost-effectiveness ratio (ICER) was estimated as the cost per quality-adjusted life-year gained over the patient's remaining lifetime. Results Under base case analysis for 3-month survival, RT was the least expensive treatment ($4,946) and provided the fewest utilities (0.112 quality-adjusted life-years). The cost of therapy for the other options was TPC $6,450, BP $11,224, and TP $18,604. Tunneled pleural catheter dominated both pleurodesis arms, namely, TPC was both less expensive and more effective. The ICER for TPC over RT was $49,978. The ICER was sensitive to complications and ability to achieve pleural sclerosis with TPC. Under base case analysis for 12-month survival, BP was the least expensive treatment ($13,057) and provided 0.59 quality-adjusted life-years. The cost of treatment for the other options was TPC $13,224, TP $19,074, and RT $21,377. Bedside pleurodesis dominated TPC and thoracentesis. Thoracoscopic pleurodesis was more effective than BP but the ICER for TP over BP was greater than $250,000. Conclusions Using decision analysis, TPC is the preferred treatment for patients with malignant pleural effusion and limited survival; BP is the most cost-effective treatment for patients with more prolonged expected survival.