A Matched Survival Analysis of Lung Transplant Recipients With Coronavirus Disease 2019-Related Respiratory Failure.

BACKGROUND: Lung transplantation is an acceptable and potentially life-saving treatment option for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome and pulmonary fibrosis. This study was conducted to determine whether recipients of lung transplantation (LT) for COVID-19-related lung disease have comparable outcomes to other recipients with a similar level of lung dysfunction. METHODS: The Organ Procurement and Transplant Network database was queried for adult LT candidates between 2006 and 2021. Recipients with COVID-19-related respiratory failure were matched 1:2 using a nearest-neighbor algorithm. Kaplan-Meier methods with log-rank tests were used to compare long-term survival. A proportional hazards model was used to calculate risk of death. RESULTS: A total of 37,333 LT candidates from all causes were compared with 334 candidates from COVID-19-related respiratory failure. COVID-19 recipients were more likely to be younger (50 vs 57 years, P < .001), male (79% vs 60%, P < .001), require extracorporeal membrane oxygenation (56.3% vs 4.0%, P < .001), and have worse lung function (lung allocation score, 82.4 vs 47.8; P < .001) at transplantation. Subsequently, 227 COVID-19 recipients were matched with 454 controls. Patients who received a transplant for COVID-19 had similar rates of mechanical ventilation, extracorporeal membrane oxygenation, postoperative complications, and functional status at discharge compared with controls. There was no difference in overall survival or risk of death from COVID-19 (hazard ratio, 0.82; 95% CI, 0.45-1.53; P = .54). CONCLUSIONS: Six-month survival for recipients of LT for COVID-19-related respiratory failure was comparable to that of other LT recipients.

Interprofessional veno-veno bypass simulation improved team confidence.

BACKGROUND: Rarely performed procedures can cause stress and communication challenges in emergency situations. A simulation was developed to practice and improve team performance and procedural workflow when it has been determined that a liver transplant patient will need veno-veno bypass. The scenario involved a patient predetermined to need veno-veno bypass to allow team members to practice procedural workflow and communication. The simulation used a checklist outlining steps of the procedure and expected communication needed among surgeon, anesthesiologist, nurses, and perfusion team members. Perfusion and nursing supplied equipment to simulate the veno-veno bypass. Debriefing and a brief survey followed the simulation. RESULTS: During the simulation participants performed steps outlined in the checklist. During debriefing, discussion occurred regarding equipment usage, step order, time documentation, and medication use. Additional discussions occurred regarding modifying perfusion tubing and supplies. Participants rated their confidence in understanding communication (4.2), ability to work with others (4.6), knowledge of supplies (4.4), and use of closed-loop communication (4.4) on a scale of 1 (not at all confident) to 5 (extremely confident) (n = 5). CONCLUSION: Participants concluded going through veno-veno bypass steps was a positive experience. Surgeons acknowledged there were multiple ways to perform this procedure and agreed it should be done the same way each time for standardization. Nursing staff commented they liked reviewing equipment in a nonemergency situation. The checklist will be turned into a resource for future operating room procedures. The perfusion team made modifications to their equipment based on surgeon recommendations. Future training is planned when new members join the team.

Illuminated Transhiatal Retractor for Mediastinal Dissection During Transhiatal Esophagectomy.

Esophagectomy following preoperative chemoradiation provides the best outcomes in the treatment of early stage esophageal carcinoma. The exposure of the mediastinum during transhiatal esophagectomy is limited. We describe our technique of mediastinal dissection during the transhiatal esophagectomy using a newly developed transhiatal retractor.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Locoregional Recurrences After Prior Chemoradiation for Advanced Esophageal Carcinoma.

Purpose: This study aimed to investigate the feasibility of stereotactic body radiation therapy (SBRT) as salvage therapy for locally recurrent esophageal cancer. We hypothesized that SBRT would provide durable treated tumor control with minimal associated toxicity in patients with progressive disease after definitive radiation, chemotherapy, and surgical resection. Methods: This single-institution retrospective study assessed outcomes in patients who received SBRT for locoregional failure of esophageal cancer after initial curative-intent treatment. Only patients who had received neoadjuvant chemoradiation (≥41.4 Gy) for esophageal cancer were selected. Subsequent surgical resection was optional but institutional follow-up by an oncologist was required. The primary endpoints of this study were gastrointestinal and constitutional toxicity, scored with the Common Terminology Criteria for Adverse Events v5.0. A secondary outcome, treated-tumor control, was assessed with RECIST v1.1. Results: Nine patients (11 locoregional recurrences) treated with SBRT were reviewed, with a median follow-up time of 10.5 months. Most patients initially presented with T3 (88.9%), N1 (55.6%), moderately differentiated (66.7%) adenocarcinoma (88.9%), and had received a median 50.4 Gy delivered over 28 fractions with concurrent carboplatin/paclitaxel chemotherapy followed by surgical resection. Median time to recurrence was 16.3 months. Median total dose delivered by SBRT was 27.5 Gy (delivered in five fractions). Two patients experienced acute grade 1 fatigue and vomiting. No patient experienced grade 3 or higher toxicity. One patient experienced failure in the SBRT treatment field at 5.8 months after treatment and six patients developed distant failure. The median progression-free survival time for SBRT-treated tumors was 5.0 months, and median overall survival time was 12.9 months. Conclusions: This single-institution study demonstrated the feasibility of SBRT for locoregional recurrence of esophageal cancer with minimal treatment-related toxicity and high rates of treated tumor control. Prospective studies identifying ideal salvage SBRT candidates for locoregional failure as well as validating its safety are needed.

Role of Barium Swallow in Diagnosing Clinically Significant Anastomotic Leak following Esophagectomy.

BACKGROUND: Barium swallow is performed following esophagectomy to evaluate the anastomosis for detection of leaks and to assess the emptying of the gastric conduit. The aim of this study was to evaluate the reliability of the barium swallow study in diagnosing anastomotic leaks following esophagectomy. METHODS: Patients who underwent esophagectomy from January 2000 to December 2013 at our institution were investigated. Barium swallow was routinely done between days 5-7 to detect a leak. These results were compared to clinically determined leaks (defined by neck wound infection requiring jejunal feeds and or parenteral nutrition) during the postoperative period. The sensitivity and specificity of barium swallow in diagnosing clinically significant anastomotic leaks was determined. RESULTS: A total of 395 esophagectomies were performed (mean age, 62.2 years). The indications for the esophagectomy were as follows: malignancy (n=320), high-grade dysplasia (n=14), perforation (n=27), benign stricture (n=7), achalasia (n=16), and other (n=11). A variety of techniques were used including transhiatal (n=351), McKeown (n=35), and Ivor Lewis (n=9) esophagectomies. Operative mortality was 2.8% (n=11). Three hundred and sixty-eight patients (93%) underwent barium swallow study after esophagectomy. Clinically significant anastomotic leak was identified in 36 patients (9.8%). Barium swallow was able to detect only 13/36 clinically significant leaks. The sensitivity of the swallow in diagnosing a leak was 36% and specificity was 97%. The positive and negative predictive values of barium swallow study in detecting leaks were 59% and 93%, respectively. CONCLUSION: Barium swallow is an insensitive but specific test for detecting leaks at the cervical anastomotic site after esophagectomy.

Reduction in airway complications after lung transplantation with novel anastomotic technique.

BACKGROUND: Bronchial anastomotic complications develop in 31% of lung transplant recipients, leading to additional operative procedures and increased morbidity. Advances in surgical technique have thus far resulted in only modestly improved outcomes. We hypothesized that creating the bronchial anastomosis at the secondary carina using a combination of running and figure-of-eight sutures would minimize donor bronchial ischemia and airway complications. METHODS: This retrospective review of a single surgeon's operative experience from 2000 to 2007 compares a new bronchial anastomotic technique with the conventional technique. The primary outcome was the occurrence of bronchial anastomotic complications requiring invasive intervention. The secondary outcome was distal airway complications. Patients were monitored for 1 year after transplant. Recipient and donor demographic data as well as relevant variables from their preoperative, perioperative, and postoperative courses were collected for analysis. These data were compared using t tests for normally distributed continuous variables, Mann-Whitney tests for nonnormally distributed continuous variables, and χ2 tests or Fisher exact test for categoric variables. Logistic regression was used to control for covariates while comparing the primary outcome between the new and conventional bronchial anastomotic techniques. RESULTS: The analysis included 230 patients, representing 407 anastomoses. The occurrence of anastomotic complications requiring intervention and distal airway complications decreased from 18.1% to 2.3% of anastomoses and 12.2% to 4.4% of patients, respectively. After controlling for available risk factors, the new technique significantly reduced both anastomotic (p<0.001) and distal (p=0.03) airway complications. CONCLUSIONS: This new anastomotic technique dramatically reduces anastomotic and distal airway complications after lung transplantation.

Synergistic protection in lung ischemia-reperfusion injury with calcineurin and thrombin inhibition.

BACKGROUND: Ischemia-reperfusion injury impairs lung transplant outcomes. The transcription factors, activator protein-1, and nuclear factor kappa B, are activated early in reperfusion and drive the development of injury. Thrombin inhibition with hirudin, and calcineurin inhibition with tacrolimus have independently been shown to ameliorate lung ischemia-reperfusion injury by reducing activator protein-1 and nuclear factor kappa B activation, respectively. However, high doses were required to achieve protection using individual agents, raising concerns about potential toxicities. We sought to determine if low-dose combination therapy reduced injury through synergistic inhibition of pretranscriptional signaling events. METHODS: Rats were pretreated with either intravenous hirudin or tacrolimus at low doses or high doses, or both at low doses, prior to undergoing left lung ischemia and reperfusion. Lungs were assessed for markers of lung injury, including bronchoalveolar lavage cytokine-chemokine content and transcription factor transactivation of activator protein-1 and nuclear factor kappa B. RESULTS: High-dose monotherapy with hirudin or tacrolimus reduced lung injury and transactivation of activator protein-1 and nuclear factor kappa B activation, respectively, whereas low-dose monotherapy with either agent did not alter transcription factor activation or lung injury compared with positive controls. Low-dose combination therapy was more protective than high-dose monotherapy with either drug, and correlated with a reduction in activation of both transcription factors and their associated cytokines. CONCLUSIONS: The significant decrease in lung injury severity and transcription factor activation with combined pathway inhibition suggests pretranscriptional signaling redundancy between the calcineurin and thrombin dependent pathways in lung reperfusion injury.

Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury.

BACKGROUND: The availability of suitable lung donors has remained a significant barrier to lung transplantation. The clinical relevance of an isolated positive Gram stain in potential donor lungs, which occurs in >80%, is unclear. Low doses of lipopolysaccharide (LPS) have been protective in several models of ischemia-reperfusion injury through a pre-conditioning response. We sought to demonstrate that low-dose LPS is protective against subsequent lung ischemia-reperfusion injury. METHODS: Pathogen-free Long-Evans rats were pre-treated with vehicle or LPS 24 hours before 90 minutes of ischemia and up to 4 hours of reperfusion. Lungs were assessed for vascular permeability, myeloperoxidase content, bronchoalveolar lavage inflammatory cell and cytokine/chemokine content, as well as nuclear translocation of nuclear factor kappaB (NFkappaB) and activator protein-1 (AP-1), and interleukin-1 receptor-associated kinase-1 (IRAK-1) and stress-activated protein kinase (SAPK) activation. RESULTS: Compared with positive controls, LPS pre-treatment resulted in reductions in vascular permeability (70%, p < 0.001), myeloperoxidase content (93%, p < 0.001), bronchoalveolar lavage inflammatory cells (91%, p < 0.001), and inflammatory cytokine/chemokine content (cytokine-induced neutrophil chemoattractant, 99%, p = 0.003; interleukin-1beta, 72%, p < 0.0001; tumor necrosis factor-alpha, 76%, p < 0.0001), NFkappaB (86%, p < 0.001) and AP-1 (97%, p < 0.001) nuclear translocation, and IRAK-1 (87%, p < 0.001) and SAPK (80%, p < 0.001) phosphorylation. CONCLUSIONS: Lipopolysaccharide pre-treatment reduced lung injury and inflammatory mediator production after subsequent exposure to ischemia-reperfusion. Understanding the clinical significance of lipopolysaccharide in donor lungs has the potential to expand and clarify donor inclusion criteria.

Alveolar macrophage secretory products effect type 2 pneumocytes undergoing hypoxia-reoxygenation.

BACKGROUND: Activation of the alveolar macrophage is centrally important to the development of lung ischemia reperfusion injury. Alveolar macrophages and type 2 pneumocytes secrete a variety of proinflammatory mediators in response to oxidative stress. The manner in which they interact and how the macrophage may influence pneumocyte responses in lung ischemia reperfusion injury is unknown. Utilizing an in vitro model of hypoxia and reoxygenation, we sought to determine if the proinflammatory response of type 2 pneumocytes to oxidative stress would be amplified by alveolar macrophage secretory products. METHODS: Cultured pneumocytes were exposed to control media or media from cultured macrophages exposed to hypoxia and reoxygenation. Pneumocytes were subsequently subjected to hypoxia and reoxygenation and assessed for both nuclear translocation of nuclear factor kappa B and inflammatory cytokine and chemokine secretion. To examine for any reciprocal interactions, we reversed the experiment, exposing macrophages to conditioned pneumocyte media. RESULTS: In the presence of media from stimulated macrophages, production of proinflammatory mediators by type 2 pneumocytes was dramatically enhanced. In contrast, exposure of the macrophage to conditioned pneumocyte media had an inhibitory effect on macrophage responses subsequently exposed to hypoxia and reoxygenation. CONCLUSIONS: The alveolar macrophage drives the development of lung reperfusion injury in part through amplification of the inflammatory response of type 2 pneumocytes subjected to hypoxia and reoxygenation.