Validation of a novel donor lung scoring system based on the updated lung Composite Allocation Score.

Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation. We performed a review of nearly 18 000 adult primary lung transplants from 2015-2022 across the US with retroactive calculations of the CAS value. The medium-CAS group (29.6-34.5) had superior 1-year posttransplant survival. Importantly, the combination of high-CAS (> 34.5) recipients with low LUNDON score (≤ 40) donors had the worst survival at 1 year compared with any other combination. Additionally, we constructed a model that predicts 1-year and 3-year survival using the LUNDON acceptability score and CAS values. These results suggest that caution should be exercised when using marginally acceptable donor lungs in high-priority recipients. The use of the LUNDON score with CAS value can potentially guide clinical decision-making for optimal donor-recipient matches for LTx.

Different-team procurements: A potential solution for the unintended consequences of change in lung allocation policy.

The new lung allocation policy has led to an increase in distant donors and consequently enhanced logistical burden of procuring organs. Though early single-center studies noted similar outcomes between same-team transplantation (ST, procuring team from transplanting center) and different-team transplantation (DT, procuring team from different center), the efficacy of DT in the contemporary era remains unclear. In this study, we evaluated the trend of DT, rate of transplanting both donor lungs, 1-year graft survival, and risk of Grade 3 primary graft dysfunction (PGD) using the Scientific Registry of Transplant Recipient (SRTR) database from 2006 to 2018. A total of 21619 patients (DT 2085, 9.7%) with 19837 donors were included. Utilization of DT decreased from 15.9% in 2006 to 8.5% in 2018. Proportions of two-lung donors were similar between the groups, and DT had similar 1-year graft survival as ST for both double (DT, HR 1.108, 95% CI 0.894-1.374) and single lung transplants (DT, HR 1.094, 95% CI 0.931-1.286). Risk of Grade 3 PGD was also similar between ST and DT. Given our results, expanding DT may be a feasible option for improving lung procurement efficiency in the current era, particularly in light of the COVID-19 pandemic.

A Clinical Nomogram for Predicting Node-positive Disease in Esophageal Cancer.

OBJECTIVE: We developed and validated a nomogram predicting the likelihood of occult lymph node metastases in surgically resectable esophageal cancers. BACKGROUND: Patients with esophageal cancer with positive lymph nodes benefit from neoadjuvant therapy, but limitations in current clinical staging techniques mean nodal metastases often go undetected preoperatively. METHODS: The National Cancer Database was queried for patients with clinical T1-3N0M0 cancer undergoing upfront esophagectomy from 2004 to 2014. Multivariable logistic regression was used to develop the risk model using both statistical significance and clinical importance criteria for variable selection. Predictive accuracy was assessed and bootstrapping was used for validation. A nomogram was constructed for presentation of the final model. RESULTS: Of 3186 patients, 688 (22%) had pathologic lymph node involvement (pN+) and 2498 (78%) had pN0 status. Variables associated with pN+ status included histology [adenocarcinoma vs squamous: odds ratio (OR) 1.75], tumor stage (T1: reference, T2: OR 1.90, T3: OR 2.17), tumor size (<1 cm: reference, 1-2 cm: OR 2.25, 2-3 cm: OR 3.82, 3-4 cm: OR 5.40, 4-5 cm: OR 5.66, ≥5 cm: OR 6.02), grade (1: reference, 2: OR 2.62, 3: OR 4.39, 4: OR 4.15, X: OR 1.87), and presence of lymphovascular invasion (absent: reference, present: OR 4.70, missing: OR 1.87), all P < 0.001. A nomogram with these variables had good predictive accuracy (Brier score: 0.14, calibration slope: 0.97, c-index: 0.77). CONCLUSIONS: We created a nomogram predicting the likelihood of pathologic lymph node involvement in patients with esophageal cancer who are clinically node negative using a generalizable dataset. Risk stratification with this nomogram could improve delivery of appropriate perioperative care.

Quantitative Computed Tomography Classification of Lung Nodules: Initial Comparison of 2- and 3-Dimensional Analysis.

OBJECTIVE: The aim of this study was to compare the performance of 2- (2D) and 3-dimensional (3D) quantitative computed tomography (CT) methods for classifying lung nodules as lung cancer, metastases, or benign. METHODS: Using semiautomated software and computerized analysis, we analyzed more than 50 quantitative CT features of 96 solid nodules in 94 patients, in 2D from a single slice and in 3D from the entire nodule volume. Multivariable logistic regression was used to classify nodule types. Model performance was assessed by the area under the receiver operating characteristic curve (AUC) using leave-one-out cross-validation. RESULTS: The AUC for distinguishing 53 primary lung cancers from 18 benign nodules and 25 metastases ranged from 0.79 to 0.83 and was not significantly different for 2D and 3D analyses (P = 0.29-0.78). Models distinguishing metastases from benign nodules were statistically significant only by 3D analysis (AUC = 0.84). CONCLUSIONS: Three-dimensional CT methods did not improve discrimination of lung cancer, but may help distinguish benign nodules from metastases.

Pulmonary cement embolization after vertebroplasty requiring pulmonary wedge resection.

BACKGROUND: Pulmonary cement embolization after vertebroplasty is a well-known complication but typically presents with minimal respiratory symptoms. Although this rare complication has been reported, the current literature does not address the need for awareness of symptoms of potentially devastating respiratory compromise. CASE DESCRIPTION: We present the case of a 29-year-old man who underwent T11 vertebroplasty and subsequently had chest pain develop several days later. His right lower lung lobe had infarcted owing to massive cement embolization to his pulmonary arterial circulation. Open pulmonary wedge resection and embolectomy were performed. The patient recovered from the embolectomy but had chronic, persistent respiratory symptoms after surgery. LITERATURE REVIEW: Operative management of vertebral compression fractures has included percutaneous vertebroplasty for the past 25 years. The reported incidence of pulmonary cement emboli after vertebroplasty ranges from 2.1% to 26% with much of this variation resulting from which radiographic technique is used to detect embolization. Symptoms of pulmonary cement embolism can occur during the procedure, but more commonly begin days to weeks, even months, after vertebroplasty. At least six deaths from cement embolization after vertebroplasty have been reported. Most cases of pulmonary cement emboli with cardiovascular and pulmonary complications are treated nonoperatively with anticoagulation. Endovascular removal of large cement emboli from the pulmonary arteries is not without risk and sometimes requires open surgery for complete removal of cement pieces. CLINICAL RELEVANCE: Pulmonary cement embolism is a potentially serious complication of vertebroplasty. If a patient has chest pain or respiratory difficulty after the procedure, chest radiography and possibly advanced chest imaging studies should be performed immediately.

Lung transplant or bust: patients' recommendations for ideal lung transplant education.

CONTEXT: Effective lung transplant education helps ensure informed decision making by patients and better transplant outcomes. OBJECTIVE: To understand the educational needs and experiences of lung transplant patients. DESIGN: Mixed-method study employing focus groups and patient surveys. SETTING: Barnes-Jewish Hospital in St Louis, Missouri. PATIENTS: 50 adult lung transplant patients: 23 pretransplant and 27 posttransplant. MAIN OUTCOME MEASURES: Patients' interest in receiving specific transplant information, the stage in the transplant process during which they wanted to receive the education, and the preferred format for presenting the information. RESULTS: Patients most wanted information about how to sustain their transplant (72%), when to contact their coordinator immediately (56%), transplant benefits (56%), immunosuppressants (54%), and possible out-of-pocket expenses (52%). Patients also wanted comprehensive information early in the transplant process and a review of a subset of topics immediately before transplant (time between getting the call that a potential donor has been found and getting the transplant). Patients reported that they would use Internet resources (74%) and converse with transplant professionals (68%) and recipients (62%) most often. DISCUSSION: Lung transplant patients are focused on learning how to get a transplant and ensuring its success afterwards. A comprehensive overview of the evaluation, surgery, and recovery process at evaluation onset with a review of content about medications, pain management, and transplant recovery repeated immediately before surgery is ideal.

Factors associated with incomplete resection for large, locally invasive non-small cell lung cancer.

Background: Large, node-negative but locally invasive non-small cell lung cancer (NSCLC) is associated with increased perioperative risk but improved survival if a complete resection is obtained. Factors associated with positive margins in this population are not well-studied. Methods: We performed a retrospective cohort study using National Cancer Database (NCDB) for adult patients with >5 cm, clinically node-negative NSCLC with evidence of invasion of nearby structures [2006-2015]. Patients were classified as having major structure involvement (azygous vein, pulmonary artery/vein, vena cava, carina/trachea, esophagus, recurrent laryngeal/vagus nerve, heart, aorta, vertebrae) or chest wall invasion (rib pleura, chest wall, diaphragm). Our primary outcome was to evaluate factors associated with incomplete resection (microscopic: R1, macroscopic: R2). Kaplan-Meier analysis and cox multivariable regression models were used to evaluate overall survival (OS), 90-day mortality, and factors associated with positive margins. Results: Among 2,368 patients identified, the median follow-up was 33.8 months [interquartile range (IQR), 12.6-66.5 months]. Most patients were white (86.9%) with squamous cell histology (47.3%). Major structures were involved in 26.4% of patients and chest wall invasion was seen in 73.6%. Four hundred and seventy-eight patients (20.2%) had an incomplete resection. Multivariable analysis revealed that black race [hazard ratio (HR) 1.568, 95% confidence interval (CI): 1.109-2.218] and major structure involvement (HR 1.412, 95% CI: 1.091-1.827) was associated with increased risk of incomplete resection and surgery at an academic hospitals (HR 0.773, 95% CI: 0.607-0.984), adenocarcinoma histology (HR 0.672, 95% CI: 0.514-0.878), and neoadjuvant chemotherapy (HR 0.431, 95% CI: 0.316-0.587) were associated with decreased risk of incomplete resection. The 5-year OS was 43.7% in the entire cohort and 28.8% in patients with positive margins and 47.5% in patients with an R0 resection. Positive margin was also associated with a significantly higher 90-day mortality rate (9.9% versus 6.7%). Conclusions: For patients with large, node-negative NSCLC invading nearby structures, R0 resection portends better survival. Treatment at academic centers, adenocarcinoma histology, and receipt of neoadjuvant chemotherapy are associated with R0 resection in this high-risk cohort.

History of Lung Transplantation.

Lung transplantation remains the only available therapy for many patients with end-stage lung disease. The number of lung transplants performed has increased significantly, but development of the field was slow compared with other solid-organ transplants. This delayed growth was secondary to the increased complexity of transplanting lungs; the continuous needs for surgical, anesthetics, and critical care improvements; changes in immunosuppression and infection prophylaxis; and donor management and patient selection. The future of lung transplant remains promising: expansion of donor after cardiac death donors, improved outcomes, new immunosuppressants targeted to cellular and antibody-mediated rejection, and use of xenotransplantation or artificial lungs.

Outcomes of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of death in the first 30 days after lung transplantation and is also associated with worse long-term outcomes. Outcomes of patients with PGD grade 3 requiring extracorporeal membrane oxygenation (ECMO) support after lung transplantation have yet to be well described. We sought to describe short- and long-term outcomes for patients with PGD grade 3 who required ECMO support. METHODS: This is a single-center retrospective cohort study of patients undergoing lung transplantation. We stratified patients with PGD grade 3 into non-ECMO, venoarterial (VA) ECMO, and venovenous (VV) ECMO groups after transplantation. We then compared the outcomes between the groups. RESULTS: Of 773 lung transplant recipients, PGD grade 3 developed in 204 (26%) at any time in the first 72 hours after lung transplantation. Of these, 13 (5%) required VA ECMO and 25 (10%) required VV ECMO support. The 30-day, 1-year, and 5-year survival in the VA ECMO group was 62%, 54%, and 43% compared with 96%, 84%, and 65% in the VV ECMO group and 99%, 94%, and 71% in the non-ECMO group. Multivariable Cox regression analysis showed that VA ECMO was associated with increased mortality (hazard ratio, 2.37; 95% CI, 1.06-5.28; P = .04). CONCLUSIONS: Patients who required VA ECMO support for PGD grade 3 have significantly worse survival compared with those who did not require ECMO and those who required VV ECMO support. This suggests that VA ECMO treatment of patients with PGD grade 3 after lung transplantation can be a predictable risk factor for mortality.

Utilizing computed tomography volumetry for size matching prior to lung transplantation: a case series.

Background: Appropriate size matching between donor and recipient is critical for successful pulmonary transplantation. Although surrogate measurements such as height and gender are often utilized to approximate predicted lung volume, these methods provide only a gross estimation with wide variability and poor predictive value. Case Description: A single center exploratory study was conducted in which four patients underwent lung transplantation (LT) with pre-operative computed tomography (CT) volumetry obtained in both the donor and recipient to facilitate decision making regarding organ size and suitability. In four cases in which CT volumetry was used, the lung volumes calculated using surrogate measurements significantly overestimated both donor and recipient lung volumes quantified by CT volumetric analysis. All recipients underwent successful LT without necessary graft downsizing. Conclusions: This is an initial report of prospectively utilizing CT volumetry as an adjunct to decision-making regarding suitability of donor lungs. In these cases, CT volumetry facilitated the confident acceptance of donor lungs that were initially predicted to be oversized based on other clinical measures.

Characteristics of donor lungs declined on site and impact of lung allocation policy change.

OBJECTIVE: National and institutional data suggest an increase in organ discard rate (donor lungs procured but not implanted) after a new lung allocation policy was introduced in 2017. However, this measure does not include on-site decline rate (donor lungs declined intraoperatively). The objective of this study is to examine the impact of the allocation policy change on on-site decline. METHODS: We used a Washington University (WU) and our local organ procurement organization (Mid-America Transplant [MTS]) database to abstract data on all accepted lung offers from 2014 to 2021. An on-site decline was defined as an event in which the procuring team declined the organs intraoperatively, and the lungs were not procured. Logistic regression models were used to investigate potentially modifiable reasons for decline. RESULTS: The overall study cohort comprised 876 accepted lung offers, of which 471 donors were at MTS with WU or others as the accepting center and 405 at other organ procurement organizations with WU as the accepting center. At MTS, the on-site decline rate increased from 4.6% to 10.8% (P = .01) after the policy change. Given the greater likelihood of non-local organ placement and longer travel distance after policy change, the estimated cost of each on-site decline increased from $5727 to $9700. In the overall group, latest partial pressure of oxygen (odds ratio [OR], 0.993; 95% confidence interval [CI], 0.989-0.997), chest trauma (OR, 2.474; CI, 1.018-6.010), chest radiograph abnormality (OR, 2.902; CI, 1.289-6.532), and bronchoscopy abnormality (OR, 3.654; CI, 1.813-7.365) were associated with on-site decline, although lung allocation policy era was unassociated (P = .22). CONCLUSIONS: We found that nearly 8% of accepted lungs are declined on site. Several donor factors were associated with on-site decline, although lung allocation policy change did not have a consistent impact on on-site decline.

Pulmonary Carcinoid Tumorlet in the Explanted Lungs for Lung Transplantation: A Case Series of 15 Patients.

BACKGROUND: Pulmonary carcinoid tumorlet (PCT) is defined as small proliferation of neuroendocrine cells that invade the adjacent basement membrane. It is often associated with chronic pulmonary inflammatory processes. However, the characteristics of PCT in end-stage lung diseases remain unclear. METHODS: We conducted a retrospective cohort study of the explanted lungs after transplantation at our institution between January 1999 and October 2020. Patients who underwent re-transplantation were excluded. RESULTS: Pulmonary carcinoid tumorlet was incidentally discovered in the explanted lungs from 15 patients (1.1%) out of 1367 lung transplants performed during the study period. Nine patients (60.0 %) were women, with a median age of 59 years (IQR: 57-62) at transplant. Underlying pulmonary indications for lung transplantation were chronic obstructive pulmonary disease (9/15, 60.0%), interstitial lung disease (2/15, 13.0%), pulmonary vascular disease (2/15, 13.0%), alpha-1 antitrypsin deficiency (1/15, 7.0%), and bronchiectasis (1/15, 7.0%). Of the patients who underwent bilateral lung transplantation (13/15, 86.7%), PCT was found in the right lung in 10 patients (10/13, 76.9%). Thirteen patients had one lesion, 1 patient had 2 lesions and 1 patient had multiple lesions. CONCLUSION: Our study shows that PCT is generally uncommon, but when it occurs, it occurs more frequently on the right side and in female patients with end-stage pulmonary disease. Chronic obstructive pulmonary disease may be a predisposing factor for developing PCT.

Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non-small cell lung cancer.

OBJECTIVE: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery. METHODS: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0. RESULTS: From April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached. CONCLUSIONS: Neoadjuvant atezolizumab in resectable stage IB to IIIB non-small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non-small cell lung cancer.

Coronavirus Disease 2019 Positivity Immediately After Lung Transplantation: A Case Report.

Management of COVID-19 in lung transplant recipients is challenging. We report a case of a 71-year-old male who underwent bilateral lung transplantation with an unexpected case of COVID-19. The patient had been fully vaccinated. The patient and donor tested negative for pretransplant COVID-19. On routine bronchoscopy on day 1 after transplant, the COVID-19 test was positive. Mycophenolic mofetil and the second dose of basiliximab were skipped, but tacrolimus and prednisone were continued. He was treated with casirivimab/imdevimab and remdesivir. He was discharged on day 14 and has had no episodes of acute rejection during the 3 months.

Lung Transplant for Pulmonary Fibrosis With Dendriform Ossification.

Dendriform pulmonary ossification (DPO) is a rare condition defined as disseminated, widespread heterotopic bone formation within the lungs. This condition is associated with restrictive pulmonary disease, such as interstitial pneumonia or fibrosis. The clinical features and pathophysiologic mechanism of DPO remain unclear, however. We report a case of a 66-year-old man with idiopathic pulmonary fibrosis accompanied by DPO who was treated with a double-lung transplant. His postoperative course was uneventful without recurrence of DPO.

Minimum Volume Standards for Surgical Care of Early-Stage Lung Cancer: A Cost-Effectiveness Analysis.

BACKGROUND: Multiple stakeholders have advocated for minimum volume standards for complex surgical procedures. The Leapfrog Group recommends that patients with non-small cell lung cancer (NSCLC) receive surgical resection at hospitals that perform at least 40 lung resections annually. However, the cost-effectiveness of this paradigm is unknown. METHODS: A cost-effectiveness analysis was performed on 90-day and 5-year horizons for patients with clinical stage I NSCLC undergoing surgical resection at hospitals stratified by Leapfrog standard. Model inputs were derived from either the literature or a propensity score-matched cohort using the National Cancer Database. For the 5-year horizon, we simulated using a Markov model with 1-year cycle. Incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. RESULTS: For the 90-day horizon, resection at a Leapfrog hospital was more costly ($25 567 vs $25 530) but had greater utility (0.185 vs 0.181 quality-adjusted life-years), resulting in an ICER of 10 506. Similarly, for the 5-year horizon, resection at a Leapfrog hospital was more costly ($26 600 vs $26 495) but more effective (3.216 vs 3.122 quality-adjusted life-years), resulting in an ICER of 1108. When the costs for long-distance travel, lodging, and loss of productivity for caregivers were factored in, the ICER was 20 499 during the 5-year horizon for resection at Leapfrog hospitals. Using a willingness-to-pay threshold of $50 000, resection at a Leapfrog hospital remained cost-effective. CONCLUSIONS: Receiving surgery for clinical stage I NSCLC at hospitals that meet Leapfrog volume standards is cost-effective. Payers and policymakers should consider supporting patient and caregiver travel to higher volume institutions for lung cancer surgery.

Transplantation of Donor Lung With Partial Anomalous Pulmonary Venous Return Using a Carrel Patch.

Partial anomalous pulmonary venous return is a rare congenital aberrancy that involves oxygen-rich pulmonary venous drainage into the right atrium instead of into the systemic circulation. This report describes a case of isolated partial anomalous pulmonary venous return of the right upper lobe in a donor lung. Successful transplantation was performed with a Carrel patch technique for left atrial cuff reconstruction using a segment of donor vena cava. This report of partial anomalous pulmonary venous return in a right donor lung describes this reconstructive approach to restore physiologic venous drainage.

Specialized Donor Care Facility Model and Advances in Management of Thoracic Organ Donors.

BACKGROUND: Donor hearts and lungs are more susceptible to the inflammatory physiologic changes that occur after brain death. Prior investigations have shown that protocolized management of potential organ donors can rehabilitate donor organs that are initially deemed unacceptable. In this review we discuss advances in donor management models with particular attention to the specialized donor care facility model. In addition we review specific strategies to optimize donor thoracic organs and improve organ yield in thoracic transplantation. METHODS: We performed a literature review by searching the PubMed database for medical subject heading terms associated with organ donor management models. We also communicated with our local organ procurement organization to gather published and unpublished information first-hand. RESULTS: The specialized donor care facility model has been shown to improve the efficiency of organ donor management and procurement while reducing costs and minimizing travel and its associated risks. Lung protective ventilation, recruitment of atelectatic lung, and hormone therapy (eg, glucocorticoids and triiodothyronine/thyroxine) are associated with improved lung utilization rates. Stroke volume-based resuscitation is associated with improved heart utilization rates, whereas studies evaluating hormone therapy (eg, glucocorticoids and triiodothyronine/thyroxine) have shown variable results. CONCLUSIONS: Lack of high-quality prospective evidence results in conflicting practices across organ procurement organizations, and best practices remain controversial. Future studies should focus on prospective, randomized investigations to evaluate donor management strategies. The specialized donor care facility model fosters a collaborative environment that encourages academic inquiry and is an ideal setting for these investigations.