Lung Transplantation in the United States for COVID-19 Related Lung Disease During the Pandemic (2597/2600).

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.

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.

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.

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.

Hyperthermic intrapleural chemotherapy: an update.

The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.

Oxygenated right ventricular assist device with a percutaneous dual-lumen cannula as a bridge to lung transplantation.

Background: Oxygenated right ventricular assist device (oxyRVAD) placement has become more streamlined with the introduction of the dual-lumen pulmonary artery cannula. Peripherally cannulated oxyRVAD may provide oxygenation support with right heart support as an alternative to venoarterial extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation. Methods: A single-institution, retrospective analysis was performed on patients placed on oxyRVAD with a dual-lumen pulmonary artery cannula with the intention of bridging to lung transplantation in 2019. Results: Four patients with idiopathic pulmonary fibrosis were placed on oxyRVAD as a bridge to transplantation. Two patients were extubated and ambulated while waiting for a lung offer, and two patients required conversion to venoarteriovenous ECMO (VAV ECMO) from oxyRVAD. The median waiting time for extracorporeal life support (ECLS) was 42 h. All patients underwent double lung transplantation. Two patients stayed on oxyRVAD, and one patient was placed on venovenous ECMO (VV ECMO) after transplantation. Primary graft dysfunction score at 72 h after transplantation was grade 1 in three patients and grade 3 in one patient. Conclusions: Peripherally cannulated oxyRVAD with percutaneous dual-lumen venous cannula could be an ambulatory bridge for lung transplantation. It is unknown whether oxyRVAD is feasible as a long-term bridge to lung transplantation.

Intraoperative support during lung transplantation.

The role of intraoperative mechanical support during lung transplantation (LTx) is essential to provide a safe hemodynamic and ventilatory status during critical intraoperative events. This hemodynamic and ventilatory stability is vital to minimize the odds of suboptimal outcomes, especially considering that, due to the scarcity of donors and the fact that more and more patients with significant comorbidities are being considered for this therapy, a more aggressive approach is often needed by the transplant centers. Hence, the attenuation of any potential injury that can happen during this complex event is paramount. While a thorough assessment of the donor and optimization of postoperative care is pursued, certainly protective intraoperative management would also contribute to better outcomes. Understanding each patient's underlying anatomy and cardiopulmonary physiology, associated with awareness of critical events during a complicated procedure like LTx, is essential for a precise indication and safe use of support. Cardiopulmonary bypass (CPB) and veno-arterial extracorporeal membrane oxygenation (VA ECMO) have been the most common approaches used, with the latter gaining popularity more recently and we have used VA ECMO exclusively for the last decade. New technologies certainly contributed to more liberal use of VA ECMO intraoperatively, enabling a protecting and physiologic environment for the newly implanted grafts. In this setting, potential prophylactic use for lung protection during a critical period is also considered.

Solid phase microextraction chemical biopsy tool for monitoring of doxorubicin residue during in vivo lung chemo-perfusion.

Development of a novel in vivo lung perfusion (IVLP) procedure allows localized delivery of high-dose doxorubicin (DOX) for targeting residual micrometastatic disease in the lungs. However, DOX delivery via IVLP requires careful monitoring of drug level to ensure tissue concentrations of this agent remain in the therapeutic window. A small dimension nitinol wire coated with a sorbent of biocompatible morphology (Bio-SPME) has been clinically evaluated for in vivo lung tissue extraction and determination of DOX and its key metabolites. The in vivo Bio-SPME-IVLP experiments were performed on pig model over various (150 and 225 mg/m2) drug doses, and during human clinical trial. Two patients with metastatic osteosarcoma were treated with a single 5 and 7 µg/mL (respectively) dose of DOX during a 3-h IVLP. In both pig and human cases, DOX tissue levels presented similar trends during IVLP. Human lung tissue concentrations of drug ranged between 15 and 293 µg/g over the course of the IVLP procedure. In addition to DOX levels, Bio-SPME followed by liquid chromatography-mass spectrometry analysis generated 64 metabolic features during endogenous metabolite screening, providing information about lung status during drug administration. Real-time monitoring of DOX levels in the lungs can be performed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy approach. Bio-SPME also extracted various endogenous molecules, thus providing a real-time snapshot of the physiology of the cells, which might assist in the tailoring of personalized treatment strategy.

Bilateral Lobar Transplants Using One Donor for Two Small-Sized Recipients.

Cadaveric lobar lung transplantation is an alternative for patients whose chest cavities have small dimensions. We present here a case where 1 donor was used for bilateral lobar transplantations in 2 high-risk patients. Coordination between the graft preparation at the back table and the 2 concomitant lung transplant teams was necessary to minimize the ischemic injury of the grafts and to plan for adequate vascular and bronchial cuffs for both implantations.

Modified In Vivo Lung Perfusion for Local Chemotherapy: A Preclinical Study With Doxorubicin.

BACKGROUND: In vivo lung perfusion (IVLP) is a promising adjuvant treatment of lung metastases, allowing the localized delivery of drugs to the lungs without systemic exposure. Previous experimental and clinical data resulted in variable efficacy and frequent toxicity. Our objectives were to demonstrate the feasibility and safety of a novel protective IVLP technique coupled with the delivery of sarcoma-based chemotherapy to the lung. METHODS: The left pulmonary artery and veins in pigs were cannulated and clamped. Left lung IVLP was performed for 4 hours. Doxorubicin (Dox) at a standard clinical dose of 75 mg/m(2) was used, followed by 150 and 225 mg/m(2). Dox 75 mg/m(2) combined with ifosfamide (Ifos) 6 g/m(2) was also tested. After IVLP, blood reperfusion was allowed for 4 hours. Lung physiology was assessed and biopsy samples were obtained for histologic assessment of acute lung injury (ALI), inflammatory profile, and cell death. Lung tissue levels, perfusate, and plasma levels of Dox were measured during the procedure. RESULTS: Lungs treated with Dox 75 mg/m(2) alone or combined with Ifos showed stable function throughout the procedure, without evidence of ALI (p = 0.12 and p = 0.36, respectively). Tissue levels of Dox were 70.3 µg/g homogeneously distributed in the lung (p = 0.12). No drug was detected systemically. Dox 150 mg/m(2) and 225 mg/m(2) showed incremental ALI. CONCLUSIONS: IVLP for 4 hours with Dox 75 mg/m(2) alone or combined with Ifos was well tolerated, without measurable ALI. High drug levels in perfusate and lung tissue were found without systemic leakage. A dose-related toxicity was observed with increases in Dox doses.

A case of retroperitoneal lymphoma presenting as pancreatic tumor.

We describe a case of non-Hodgkin's lymphoma arising in the peripancreatic retroperitoneal lymph node and extending into the pancreatic parenchyma. Abdominal ultrasonogram and computed tomography of the abdomen showed an mass in the head of pancreas with absence of extrapancreatic disease and no direct tumor extension to the portal vein or superior mesenteric artery. Laparotomy demonstrated a large pancreatic mass with no obstruction of common bile duct or encasement of portal vein and superior mesenteric artery and a pancreaticoduodenectomy was performed. He received chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone. The patient is alive and in remission with a follow-up time of 24 months.