Lymphovascular Invasion is an Independent Negative Prognostic Factor in Esophageal Adenocarcinoma.

BACKGROUND: The significance of lymphovascular invasion (LVI) in esophageal adenocarcinoma (EAC) has not yet been described. Potential utility as an adjunct to current staging guidelines remains unknown. METHODS: The National Cancer Database was queried from 2006 to 2020. Univariate and multivariable models, Kaplan Meier method, and log-rank test were used. Subgroup analyses by pN stage were conducted. RESULTS: Of 9,689 patients, 23.2% had LVI. LVI was an independent prognostic factor (hazard ratio [HR] 1.401, 95% confidence interval [CI] 1.307-1.502, p < 0.0001) with reduction in median survival to 20.0 months (95% CI 18.9-21.4) from 39.7 months (95% CI 37.8-42.3, p < 0.0001). Multivariable survival analysis adjusted on pN and pT stage found that patients with LVI had decreased survival in a given pN stage (p < 0.001). pN0/LVI+ patients had a similar prognosis to the higher staged pN1/LVI- (28.6 months), although pN1/LVI- patients did slightly worse (p = 0.0135). Additionally, patients with pN1/LVI+ had equivalent survival compared with pN2/LVI- (p = 0.178) as did pN2/LVI+ patients compared with pN3/LVI- (p = 0.995). CONCLUSIONS: In these data, LVI is an independent negative prognostic factor in EAC. LVI was associated with a survival reduction similar to an upstaged nodal status irrespective of T stage. Patients with LVI may be better classified at a higher pN stage.

Lung Transplantation in the United States for COVID-19 Related Lung Disease During the Pandemic.

PURPOSE: Lung transplantation (LTx) is a potential intervention for end-stage COVID-19 lung disease. Current literature is sparse regarding the outcomes of LTx for COVID-19 related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). This study aims to characterize outcomes and patterns of LTx for COVID-19 related lung disease throughout the pandemic. METHODS: Patients who underwent LTx during the pandemic for COVID-19 related lung disease were retrospectively identified using the UNOS registry. Demographics, as well as outcomes measures and nationwide patterns of care were collected and analyzed. RESULTS: A total of 510 adult cases of LTx for COVID-19 (259 ARDS, 251 PF) were compared to 4,031 without COVID-19 (3,994 PF, 37 ARDS). Patients who received LTx for COVID-19 ARDS did not differ in 2-year survival when compared to those with COVID-19 PF (81.9% vs 77.2%, p = 0.4428). Compared to non-COVID-19 etiologies, COVID-19 ARDS patients had higher rates of stroke (2.3% vs 0%, p = 0.0005), lower rates of graft failure (12.8% vs 36.1%, p = 0.0003) and post-transplant ECMO (29.6% vs 41.7%, p = 0.0002), and improved 2-year survival following LTx (81.9% vs 61.7%, p = 0.0064). No difference in 2-year survival following LTx was observed between patients with COVID-19 and non-COVID-19 PF (77.2% vs 71.8%, p = 0.34). Rates of LTx spiked with variant emergence and declined with rounds of vaccination. CONCLUSION: Our results are consistent with early reports of survival outcomes following LTx for COVID-19 ARDS and PF while providing an increased layer of granularity. LTx may be considered as a safe and effective intervention for COVID-19 lung disease.

Lobar versus sublobar resection for atypical lung carcinoid: An analysis from the National Cancer Database.

BACKGROUND: There is a knowledge gap regarding lobar versus sublobar resection for atypical carcinoid (AC) of the lung. As such, the authors sought to understand and analyze the outcomes of sublobar resection versus lobectomy in this patient population. METHODS: A retrospective analysis using the National Cancer Database was performed to compare overall survival (OS) between patients treated with lobectomy and patients treated with sublobar resection for AC of the lung between the years 2004 and 2016. Patient characteristics were compared with χ2 tests. The Kaplan-Meier method was used to estimate OS distributions, and the log-rank test was used to compare distributions by treatment strategy. A multivariable Cox regression model was used to assess associations between the treatment strategy and OS. A propensity score matching method was also implemented to further eliminate treatment selection bias in the study sample. RESULTS: The database identified 669 patients with T1-T4 and N0-N3 lung ACs that were surgically resected. Unadjusted Kaplan-Meier survival curves did not demonstrate an OS difference between lobectomy and sublobar resection (p = .094). After propensity score matching, curves demonstrated a numerical improvement in OS with lobectomy; however, it was not statistically significant (p = .5). In a subgroup analysis, lobectomy and node-negative disease were associated with the best OS, whereas sublobar resection and node-positive disease were associated with the worst OS (p < .0001). Nodal involvement was associated with worse survival, regardless of surgical treatment (p < .0001). CONCLUSIONS: In patients with T1-T4 and N0-N3 ACs of the lung, lobectomy was not associated with an improvement in OS in comparison with sublobar resection.

First Use of a Novel Extracorporeal Life Support System: Successful Application in Tracheoesophageal Fistula Repair.

Extracorporeal life support, commonly referred to as extracorporeal membrane oxygenation (ECMO), is indicated when conventional medical and surgical measures fail to support a patient during cardiac or respiratory failure. Increased use of ECMO in recent years has led to innovation that has improved safety in appropriate candidates. This has resulted in the application of novel approaches to complex surgical problems. Herein, we describe a simple, novel, and new-to-market ECMO circuit used for successful perioperative veno-venous ECMO support of a patient undergoing complex repair of a tracheoesophageal fistula. We believe that this circuit and its use for intra-and post-operative extracorporeal support provides a framework for safe and simple ECMO support in the future, including perioperative support for patients undergoing complicated and challenging thoracic procedures.

Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Platelet transfusion is associated with 90-day and 1-year mortality for adult patients requiring veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Studies examining one-year mortality respecting component blood transfusion are sparse. We hypothesize that component blood product transfusions are negatively associated with 90-day and 1-year survival for all patients requiring veno-arterial (VA) or veno-venous (VV) ECMO. STUDY DESIGN AND METHODS: This was an IRB-approved retrospective cohort analysis of 676 consecutive patients requiring ECMO at the University of Pittsburgh between 2005 and 2016. Patients were analysed both as an entire cohort and as two subsets with respect to ECMO modality (VA vs. VV). Additional data collected and analysed included patient characteristics, laboratory values and blood product transfusion. RESULTS: Multivariable analysis revealed that platelet transfusion was associated with 90-day mortality (OR: 1·05, P = 0·037) and one-year mortality for the entire cohort (OR = 1·05, P = 0·046,). Platelet transfusion volume was also associated with mortality in the VA-ECMO subset of patients at both 90 days (OR = 1·08, P = 0·03) and one year (OR: 1·11, P = 0·014). Age, peak International Normalized Raton ECMO, nadir haemoglobin (on ECMO) and final haemoglobin (after ECMO) were significantly associated with mortality for patients requiring VA-ECMO. For VV-ECMO patients, age, INR and peak creatinine on ECMO were associated with mortality. No individual component blood product was associated with one-year mortality for patients requiring VV-ECMO. CONCLUSION: Platelet transfusion was associated with increased 90-day and 1-year mortality for patients requiring VA-ECMO.

Nitrite attenuates mitochondrial impairment and vascular permeability induced by ischemia-reperfusion injury in the lung.

Primary graft dysfunction (PGD) is directly related to ischemia-reperfusion (I/R) injury and a major obstacle in lung transplantation (LTx). Nitrite (NO2-), which is reduced in vivo to form nitric oxide (NO), has recently emerged as an intrinsic signaling molecule with a prominent role in cytoprotection against I/R injury. Using a murine model, we provide the evidence that nitrite mitigated I/R-induced injury by diminishing infiltration of immune cells in the alveolar space, reducing pulmonary edema, and improving pulmonary function. Ultrastructural studies support severe mitochondrial impairment in the lung undergoing I/R injury, which was significantly protected by nitrite treatment. Nitrite also abrogated the increased pulmonary vascular permeability caused by I/R. In vitro, hypoxia-reoxygenation (H/R) exacerbated cell death in lung epithelial and microvascular endothelial cells. This contributed to mitochondrial dysfunction as characterized by diminished complex I activity and mitochondrial membrane potential but increased mitochondrial reactive oxygen species (mtROS). Pretreatment of cells with nitrite robustly attenuated mtROS production through modulation of complex I activity. These findings illustrate a potential novel mechanism in which nitrite protects the lung against I/R injury by regulating mitochondrial bioenergetics and vascular permeability.

Patent foramen ovale repair at the time of double lung transplantation: Necessary or not?

INTRODUCTION: Patient foramen ovale (PFO) is a common and often incidental intraoperative finding during lung transplantation (LTx). We sought to characterize the potential outcomes related to the decision making of whether the PFO was repaired or left unrepaired. METHODS: We retrospectively evaluated bilateral LTx recipients between 2005 and 2015 from our prospective database. Incidence of postoperative stoke, 90-day mortality, and overall survival was compared between the PFO-positive and PFO-negative groups, and secondly compared between repaired PFO (rPFO) and non-repaired PFO (nrPFO) groups. RESULTS: A total of 831 LTx recipients were analyzed: 185 PFO-positive (140 nrPFO, 45 rPFO) and 646 PFO-negative. Study groups were similar with regard to age and comorbidity. The presence of PFO was not associated with a difference in postoperative stroke (P = .89) or 90-day mortality (P = .64). In patients with PFO, intraoperative repair resulted in a lower, but non-significant rate of stroke (0% vs 5%; P = .20) and no difference in mortality (P = .26). As expected, PFO and PFO repair were both associated with a higher incidence of cardiopulmonary bypass utilization, but no difference in pump-related complications. CONCLUSIONS: The protective effect of PFO repair remains unclear. However, it is not associated with an increased incidence of stroke or postoperative mortality following LTx.

Detrimental Association of Hypogammaglobulinemia With Chronic Lung Allograft Dysfunction and Death Is Not Mitigated by On-Demand Immunoglobulin G Replacement After Lung Transplantation.

BACKGROUND:: Hypogammaglobulinemia (HGG), immunoglobulin G (IgG) <700 mg/dL, is associated with infections, chronic lung allograft dysfunction, and death following lung transplantation. This study evaluates the use of on-demand intravenous IgG in lung transplant recipients with HGG. MATERIALS AND METHODS:: This single-center retrospective cohort study of adult lung recipients evaluated 3 groups, no, untreated (u), or treated (t) HGG at first IgG administration or a matched time posttransplant. Primary outcome was freedom from allograft dysfunction. Secondary outcomes included development of advanced dysfunction, rejection, infection burden, and mortality. RESULTS:: Recipients included 484 (no HGG: 76, uHGG: 192, tHGG: 216). Freedom from chronic allograph dysfunction was highest in the non-HGG group 2 years post-enrollment (no HGG 77.9% vs uHGG 56.4% vs tHGG 52.5%; P = .002). Freedom from advanced dysfunction was significantly different 2 years post-enrollment (no HGG 90.5% vs uHGG 84.7% vs tHGG 75.4%; P = .017). Patients without HGG and those with uHGG had less mortality at 2 years post-enrollment (no HGG 84.2% vs uHGG 81.3% vs tHGG 64.8%; P < .001). Gram-negative pneumonias occurred more often in the tHGG group ( P = .02). CONCLUSIONS:: Development of chronic lung allograft dysfunction, patient survival, rejection burden, and key infectious outcomes in lung transplant recipients were still problematic in the context of on-demand IgG therapy. Prospective studies are warranted.

Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation.

Refractory acute cellular rejection (rACR) is associated with death and bronchiolitis obliterans syndrome (BOS) post-lung transplantation. We report the largest cohort of lung transplant recipients (LTRs) treated with rescue alemtuzumab for rACR or BOS. RACR outcomes included burden of ACR 30 days before and 180 days after rescue assessed by a novel composite rejection standardized score (CRSS, range 0-6) and freedom from ≥A2 ACR. BOS outcomes included freedom from BOS progression and FEV1 decline >10%. Univariate parametric and nonparametric statistical approaches were used to assess treatment response. Kaplan-Meier method with log rank conversion was used to assess freedom from events. Fifty-seven alemtuzumab doses (ACR 40 and BOS 17) given to 51 patients were included. Median time to rescue was 722 (IQR 42-1403) days. CRSS declined significantly (3 vs 0.67, P<0.001) after rescue. Freedom from ≥A2 was 62.5% in rACR. Freedom from BOS progression was 52.9% at 180 days in the BOS cohort. Freedom from FEV1 decline >10% was 70% in BOS grade 1 and 14.3% in advanced BOS grades 2-3. Infections developed in 72.5% and 76.5% of rACR and BOS groups. Rescue alemtuzumab appears useful for rACR. Patients with BOS 1 may have transient benefit, and patients with advanced BOS seem not to respond to alemtuzumab.

Extracorporeal Support During Bilateral Sequential Lung Transplantation in Patients With Pulmonary Hypertension: Risk Factors and Outcomes.

OBJECTIVE: To identify preoperative predictors of extracorporeal support in patients with pulmonary hypertension (PH) undergoing bilateral sequential lung transplantation (LTx), and to examine outcomes associated with the use of extracorporeal support. DESIGN: Retrospective, observational study. SETTING: Single organ transplantation and tertiary care university medical center. PARTICIPANTS: Adults with PH (preoperative mean pulmonary artery pressure (mPAP)≥25 mmHg) who underwent primary bilateral sequential LTx during 2007 to 2013. MEASUREMENTS AND MAIN RESULTS: Of 262 patients with PH undergoing LTx, extracorporeal support was initiated intraoperatively in 149 (57%). Preoperative severe right ventricle (RV) dysfunction and moderate or severe tricuspid regurgitation (TR) were associated with extracorporeal support. In the remaining 208 patients without those factors, increasing preoperative oxygen requirement (odds ratio [OR] 1.30 per 1 L/min, 95% confidence intervals [CI] 1.11-1.52, p = 0.001), presence of RV dilation (OR 2.77, 95% CI 1.28-6.02, p = 0.010), and mPAP (OR 1.33 per 5-mmHg increase in mPAP, 95% CI 1.04-1.70, p = 0.021) were associated independently with extracorporeal support in the multivariable model. Analysis of 49 propensity-matched pairs showed longer intensive care unit (5 v 14 days, p = 0.006) and hospital stays (27 v 39 days, p = 0.016) and increased need for tracheostomy (16% v 41%, p = 0.017) in patients exposed to extracorporeal support but no differences in 30-day mortality, stroke, myocardial infarction, or dialysis. CONCLUSIONS: Severity of RV dysfunction, TR, RV dilatation, increasing oxygen requirement, and increasing mPAP showed significant associations with the need for extracorporeal support during LTX in patients with PH. Extracorporeal support was associated with increased length of stay and tracheostomy but not with mortality or other complications. © 2016 Elsevier Inc. All rights reserved.

Lung Transplantation for People Living With HIV: Promising Mid-term Outcomes.

BACKGROUND: With increasing life expectancy, patients with HIV are more commonly acquiring other chronic diseases, such as end-stage lung disease, for which transplant may be the only effective solution. Until recently, HIV infection was considered a contraindication to lung transplant (LTx). As LTx in people living with HIV (PLWH) becomes more common, there remain limited data on outcomes in this population. METHODS: Using the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research file, we identified LTx recipients with HIV by either serostatus or nucleic acid testing. A control group of confirmed HIV-negative LTx recipients was propensity score matched on age, body mass index, primary diagnosis, and year of transplant. Patient characteristics, transplant parameters, survival, and postoperative outcomes were compared. RESULTS: Fifty-nine LTx recipients with HIV were identified and compared with 236 HIV-negative controls. Among PLWH, cytomegalovirus status was more frequently positive (76.3% versus 58.9%, P = 0.014), and the median Lung Allocation Score at match was higher (44 versus 39, P = 0.004). PLWH were more likely to undergo dialysis postoperatively (18.6% versus 8.9%, P = 0.033), although other complication rates were similar. Fifty-three percent of LTx for PLWH occurred since 2020. One-year survival for PLWH was 91.2% versus 88.6% for controls ( P = 0.620). Three-year survival for a smaller subset was also not statistically significant (HIV versus control: 82.6% versus 77.8%, respectively, P = 0.687). CONCLUSIONS: There was no difference in 1-y survival for LTx recipients living with HIV compared with a matched control group, supporting this group of patients as viable candidates for LTx.

Lung Transplant Outcomes for Idiopathic Pulmonary Fibrosis: Are We Improving?

BACKGROUND: After implementation of the Lung Allocation Score in 2005, idiopathic pulmonary fibrosis (IPF) emerged as the most common indication for lung transplantation (LT) in the United States. The age and comorbidity of patients undergoing LT have since increased, and the indications for LT have evolved. However, limited data have been used to analyze more recent outcomes among the IPF population. METHODS: This study analyzed LTs for the primary indication of IPF by using the United Network for Organ Sharing database. An eras-based analysis was performed, comparing patient characteristics, survival, and related outcomes during 2005 to 2009 (era 1) and 2010 to 2014 (era 2) with χ2, Wilcoxon rank sum, and Kaplan-Meier analyses. The study compared 1-year survival from 2005 to 2020 and survival at milestones ranging from 1 month to 5 years. Two adjusted Cox proportional hazards models were conducted: 5-year survival by era and 1-year survival annually from 2010 to 2020. RESULTS: From era 1 (n = 1818) to era 2 (n = 3227), the median age of LT recipients increased from 61 to 63 years (P < .001). The percentage of patients in the intensive care unit before LT climbed from 7.7% to 12.1% (P < .001), and the percentage of patients with diabetes grew from 17.9% to 19.4% (P = .003). Despite increased severity of illness, 5-year survival increased from 51.9% in era 1 to 55.2% in era 2 (P = .02). Adjusted modeling indicated that LT during era 2 featured a 17% hazard reduction compared with era 1 (hazard ratio, 0.83; 95% CI, 0.76-0.91). CONCLUSIONS: Survival is improving for patients undergoing LT for IPF, despite the challenges of transplant recipients with progressively higher risk profiles.

Dynamic volume-outcome association for esophagectomies: Do current volume thresholds still apply?

BACKGROUND: It is unknown if the current minimum case volume recommendation of 20 cases per year per hospital is applicable to contemporary practice. METHODS: Patients undergoing esophageal resection between 2005 and 2015 were identified in the National Cancer Database. High, medium, and low-volume hospital strata were defined by quartiles. Adjusted odds ratios and adjusted 30-day mortality between low-, medium-, and high-volume hospitals were calculated using logistic regression analyses and trended over time. RESULTS: Only 1.1% of hospitals had ≥20 annual cases. The unadjusted 30-day mortality for esophagectomy was 3.8% overall. Unadjusted and adjusted 30-day mortality trended down for all three strata between 2005 and 2015, with disproportionate decreases for low-volume and medium-volume versus high-volume hospitals. By 2015, adjusted 30-day mortality was similar in medium- and high-volume hospitals (odds ratio 1.35, 95% confidence interval 0.96-1.91). For hospitals with 20 or more annual cases the adjusted 30-day mortality was 2.7% overall. To achieve this same 30-day mortality the minimum volume threshold had lowered to 7 annual cases by 2015. CONCLUSION: Only 1.1% of hospitals meet current volume recommendations for esophagectomy. Differential improvements in postoperative mortality at low- and medium- versus high-volume hospitals have led to 7 cases in 2015 achieving the same adjusted 30-day mortality as 20 cases in the overall cohort. Lowering volume thresholds for esophagectomy in contemporary practice would potentially increase the proportion of hospitals able to meet volume standards and increase access to quality care without sacrificing quality.

Donor and recipient risk factors for the development of primary graft dysfunction following lung transplantation.

Primary Graft Dysfunction (PGD) is a major cause of both short-term and long-term morbidity and mortality following lung transplantation. Various donor, recipient, and technical risk factors have been previously identified as being associated with the development of PGD. Here, we present a comprehensive review of the current literature as it pertains to PGD following lung transplantation, as well as discussing current strategies to mitigate PGD and future directions. We will pay special attention to recent advances in lung transplantation such as ex-vivo lung perfusion, thoracoabdominal normothermic regional perfusion, and up-to-date literature published in the interim since the 2016 ISHLT consensus statement on PGD and the COVID-19 pandemic.

Extracorporeal membrane oxygenation for general thoracic surgery: case series and narrative review.

Background and Objective: Extracorporeal membrane oxygenation (ECMO) has historically been utilized as a temporary life support option for patients with severe cardiac and pulmonary dysfunction. Recent advancements have enabled the safe application of ECMO in a wider variety of patients; we present a review of its use in patients undergoing general thoracic procedures supported by a case series at our institution. Methods: We review current literature focusing on ECMO applications in thoracic surgery outside of the traditional use. Additionally, we offer three cases of ECMO utilization to illustrate success stories and key lessons learned regarding the use of ECMO in general thoracic surgery. Key Content and Findings: Technologic advancements and enhanced safety profiles have enabled the safe application of ECMO in a wide array of patients far beyond the historic indications of cardiogenic shock and acute respiratory distress syndrome (ARDS). It is now feasible to consider ECMO for management of acute thoracic emergencies, as well as to better facilitate operative safety in complex general thoracic surgical procedures. Both venovenous and venoarterial ECMO can be utilized in carefully selected patients to provide cardiopulmonary support while enabling improved visualization and increased mobilization without concern for respiratory and/or cardiac compromise. Conclusions: Enthusiasm for the use of ECMO has increased in recent years. What was once considered a salvage therapy in cases of life-threatening cardiopulmonary decompensation now plays an increasingly important role in the safe conduct of complex thoracic surgery procedures, provides much needed time for organ recovery, and offers acute resuscitation options. This shift broadens our ability to deliver life-saving care to patients that previously would have otherwise had limited treatment options.