Extending the age criteria of lung transplant donors to 70+ years old does not significantly affect recipient survival.

OBJECTIVES: To determine the impact of older donor age (70+ years) on long-term survival and freedom from chronic lung allograft dysfunction in lung transplant (LTx) recipients. METHODS: A retrospective single-center study was performed on all LTx recipients from 2002 to 2017 and a modern subgroup from 2013 to 2017. Recipients were stratified into 4 groups based on donor lung age (<18, 18-55, 56-69, ≥70 years). Donor and recipient characteristics were compared using χ2 tests for differences in proportions and analysis of variance for differences in means. Univariable and multivariable Cox regression was used to describe differences in long-term survival and freedom from chronic lung allograft dysfunction. RESULTS: Between 2002 and 2017, 1600 LTx were performed, 98 of which were performed from donors aged 70 years or older. Recipients of 70+ years donor lungs were significantly older with a mean age of 55.5 ± 12.9 years old (P = .001) and had more Status 3 (urgent) recipients (37.4%, P = .002). After multivariable regression, there were no significant differences in survival or freedom from chronic lung allograft dysfunction between the 4 strata of recipients. CONCLUSIONS: Lung transplantation using donors 70 years old or older can be considered when all other parameters suggest excellent donor lung function without compromising short- or long-term outcomes.

Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial.

Importance: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear. Objective: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment. Design, Setting, and Participants: This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre-University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic evidence of advanced lung cancer prior to a tissue diagnosis. Interventions: Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care. Main Outcome and Measures: The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after tissue diagnosis. Results: Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (P < .001). Among the ACCELERATE cohort, the median turnaround time from sample collection to genotyping results was 7 days (IQR, 6-9 days) for plasma and 23 days (IQR, 18-28 days) for tissue NGS (P < .001). Of the 90 patients with advanced nonsquamous NSCLC, 21 (23%) started targeted therapy before tissue NGS results were available, and 11 (12%) had actionable alterations identified only through plasma testing. Conclusions and Relevance: This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing. Trial Registration: ClinicalTrials.gov Identifier: NCT04863924.

Peroneus brevis muscle flap for a 20-year-old neuroischemic diabetic ulcer induced by traumatic injury: a case report detailing the efficacy of advanced combined treatment modalities for chronic wound closure.

INTRODUCTION: Peroneus brevis flaps provide a viable option to achieve soft tissue coverage in hard-to-heal lower extremity wounds, specifically those to the lateral ankle and hindfoot. CASE REPORT: The authors present a unique case of a patient with a 20-year-old wound dehiscence complicated by osteomyelitis. The wound was a complication from a lateral extensile incision utilized during prior calcaneal open reduction and internal fixation. Due to many factors, including multiple comorbidities, the patient could not obtain complete healing despite IV antibiotics, vascular optimization, local wound care, surgical debridement, and grafting. Wound closure was ultimately achieved with a PB muscle flap. Adjunctive therapies also utilized included multilevel ring external fixation, negative pressure wound therapy, and hyperbaric oxygen therapy. On follow-up 32 months after the procedure, the patient continued to be wound free and satisfied with the results. CONCLUSIONS: This case report demonstrates the utility of PB muscle flaps for hard-to-heal lower extremity wounds in patients with comorbidities.

Outcomes of lung transplantation from donors with a history of substance abuse.

OBJECTIVE: The study objective was to determine whether donor substance abuse (opioid overdose death, opioid use, cigarette or marijuana smoking) impacts lung acceptance and recipient outcomes. METHODS: Donor offers to a single center from 2013 to 2019 were reviewed to determine if lung acceptance rates and recipient outcomes were affected by donor substance abuse. RESULTS: There were 3515 donor offers over the study period. A total of 154 offers (4.4%) were opioid use and 117 (3.3%) were opioid overdose deaths. A total of 1744 donors (65.0%) smoked cigarettes and 69 donors (2.6%) smoked marijuana. Of smokers, 601 (35.0%) had less than 20 pack-year history and 1117 (65.0%) had more than 20 pack-year history. Substance abuse donors were younger (51.5 vs 55.2 P < .001), more often male (65.6 vs 54.8%, P < .001), more often White (86.2 vs 68.7%, P < .001), and had hepatitis C (8.3 vs 0.8%, P < .001). Donor acceptance was significantly associated with brain dead donors (odds ratio, 1.56, P < .001), donor smoking history (odds ratio, 0.56, P < .001), hepatitis C (odds ratio, 0.35, P < .001), younger age (odds ratio, 0.98, P < .001), male gender (odds ratio, 0.74, P = .004), and any substance abuse history (odds ratio, 0.50, P < .001), but not opioid use, opioid overdose death, or marijuana use. Recipient survival was equivalent when using lungs from donors who had opioid overdose death, who smoked marijuana, or who smoked cigarettes for less than 20 patient-years or more than 20 patient-years, and significantly longer in recipients of opioid use lungs. There was no significant difference in time to chronic lung allograft dysfunction for recipients who received lungs from opioid overdose death or with a history of opioid use, marijuana smoking, or cigarette smoking. CONCLUSIONS: Donor acceptance was impacted by cigarette smoking but not opioid use, opioid overdose death, or marijuana use. Graft outcomes and recipient survival were similar for recipients of lungs from donors who abused substances.

Influence of anterior tumor location on survival after resection of lung cancer invading the thoracic inlet (Pancoast tumors).

OBJECTIVE: Superior sulcus tumors are a challenging subset of non-small cell lung carcinomas invading the thoracic inlet. In this study, we determined whether the location of the tumor along the first rib had an influence on survival. METHODS: We performed a review of 92 consecutive patients undergoing surgery for non-small cell lung carcinomas invading the thoracic inlet between January 1996 and June 2021. Tumor location was categorized into anterior and posterior based on predefined zones. RESULTS: In total, 21 tumors were located anteriorly (23%) and 71 posteriorly (77%). The rate of R0 resection (81% vs 87%; P = .4) and pathological complete response to induction therapy (33% vs 37%; P = .8) were similar between locations. After a median follow-up of 5.8 years (range, 0.8-24 years), 49 patients died for an overall survival of 48% (95% CI, 38%-59%) at 5 years. The 5-year survival was favorably influenced by R0 (vs R1) resection (51% vs 29%; P = .02), pathological complete response (vs no pathological complete response) (69% vs 31%; P = .03), posterior (vs anterior) location (56% vs 22%; P = .01), and ≤60 (vs >60) years of age (61% vs 37%; P = .007). Compared with posterior tumors, anterior tumors were associated with higher risk of systemic recurrence and significantly greater survival benefit from pathological complete response. Anterior tumors remained an independent predictor of worse survival in multivariate analysis (hazard ratio, 2.3; 95% CI, 1.2-4.5; P = .01). CONCLUSIONS: The anatomical location of the tumor affects survival after resection of non-small cell lung carcinomas invading the thoracic inlet. Anterior tumors have greater propensity to metastasize and may derive greater benefit from optimal systemic therapy than posterior tumors.

Ex vivo lung evaluation of single donor lungs when the contralateral lung is rejected increases safe use.

OBJECTIVE: The decision to perform a single-lung transplant (SLT) when the contralateral donor lung is rejected is a challenging scenario. The introduction of ex vivo lung perfusion (EVLP) has improved donor lung assessment, and we hypothesize that it has improved SLT outcomes in this setting. METHODS: A retrospective single-center review of all SLTs performed between 2000 and 2017 was performed in which the years 2000 to 2008 were considered the "pre-EVLP era" and 2009 to 2017 the "EVLP era." Recipients of SLT lungs when the contralateral lung was declined were classified into 3 groups: (1) Pre-EVLP era, (2a) EVLP era but EVLP not used, and (2b) EVLP era and EVLP used. The outcomes of interest were survival, time-to-extubation, and intensive care unit and hospital stay. RESULTS: Among 1692 transplants between 2000 and 2017, 244 (14%) were SLT. SLT rate was similar between eras (pre-EVLP 16% vs EVLP 15%), but more SLTs were performed where the contralateral lung was declined in the EVLP era (pre-EVLP 32% vs EVLP 45%, P = .04). Lungs evaluated on EVLP had lower procurement partial pressure of oxygen and were more often from donation after cardiac death donors. Recipients were generally also sicker, with a greater proportion of rapidly deteriorating recipients. Despite this, outcomes were similar between eras with a trend towards lower 30-day mortality in the EVLP era. CONCLUSIONS: The availability of EVLP allowed for better evaluation of marginal single lungs when the contralateral was declined. This has led to increased use rates with preserved outcomes despite use of more extended criteria organs.

Plasma-first: accelerating lung cancer diagnosis and molecular profiling through liquid biopsy.

Introduction: Molecular profiling of tumor tissue is the gold standard for treatment decision-making in advanced non-small cell lung cancer (NSCLC). Results may be delayed or unavailable due to insufficient tissue, prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma testing in the initial diagnostic workup for patients with suspected advanced lung cancer. Methods: Patients with ⩽15 pack-year smoking history and suspected advanced lung cancer referred to the lung cancer rapid diagnostic program underwent plasma circulating-tumor DNA testing using a DNA-based mutation panel. Tissue testing was performed per standard of care, including comprehensive next-generation sequencing (NGS). The primary endpoint was time from diagnostic program referral to cancer treatment in stage IV NSCLC patients (Cohort A) compared to a contemporary cohort not enrolled in the study (Cohort B) and an historical pre-COVID cohort referred to the program between 2018 and 2019 (Cohort C). Results: From January to June 2021, 20 patients were enrolled in Cohort A; median age was 70.5 years (range 33-87), 70% were female, 55% Caucasian, 85% never smokers, and 75% were diagnosed with NSCLC. Seven had actionable alterations detected in plasma or tissue (4/7 concordant). Fusions, not tested in plasma, were identified by immunohistochemistry for three patients. Mean result turnaround time was 17.8 days for plasma NGS and 23.6 days for tissue (p = 0.10). Mean time from referral to treatment initiation was significantly shorter in cohort A at 32.6 days (SD 13.1) versus 62.2 days (SD 31.2) in cohort B and 61.5 days (SD 29.1) in cohort C, both p < 0.0001. Conclusion: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC can lead to faster molecular results and shorten time to treatment even with smaller DNA panels. An expansion study using comprehensive NGS plasma testing with faster turnaround time is ongoing (NCT04862924).

Outcomes of lung transplantation at a Canadian center using donors declined in the United States.

OBJECTIVES: Donor lungs from the United States can be offered by US organ procurement organizations to Canada if no American centers accept them. The purpose of this study is to evaluate outcomes of patients undergoing transplant at a single center in Canada using declined lungs from the United States and to compare these outcomes to patients receiving lungs from Canadian donors. METHODS: A single-center retrospective review of recipients receiving lung transplantation between January 2009 and October 2019 was performed. An Organ Procurement and Transplantation Network standard transplant analysis and research-limited dataset as of August 17, 2021, was provided by the United Network for Organ Sharing. De-identified patient-level data were extracted from the standard transplant analysis and research file to identify lung offers made by US organ procurement organizations, declined by US lung centers, and transplanted by the University Health Network within the study time frame. We divided the analysis into 2 groups: recipients receiving donor lungs from Canada and recipients receiving donor lungs from the United States. Donor and recipient characteristics between the 2 groups were compared. Primary end point was proportional survival over a 10-year period. Secondary end points included 30-day mortality, intensive care unit and hospital length of stay, severe primary graft dysfunction, and incidence of chronic lung allograft dysfunction. RESULTS: During the study period, 1424 lung transplants were performed at our center. Of these, 124 (8.7%) were performed using donors from the United States. The incidence of transplants using US donors increased from 5% (5 out of 102) in 2009 to 15% (30 out of 200) in 2018. US donors were younger (aged 41 vs 47 years; P = .004), less likely to be from donors after cardiac death (9.6% vs 20%; P = .008), had higher use of ex vivo lung perfusion (EVLP, 46% vs 27%; P = .0002), and higher incidence of positive nucleic acid test for hepatitis C (16% vs 0.7%; P = .0001). Although the incidence of EVLP utilization was higher in the US lungs versus Canada lungs, more than half of US lungs (54%) proceeded directly to transplantation. Similar short- and long-term outcomes were observed between the 2 groups, including overall survival (hazard ratio, 1.12; 95% CI, 0.85-1.47; P = .40) CONCLUSIONS: Lung transplantation using donor lungs declined by multiple centers in the United States resulted in similar short- and long-term outcomes compared with donor lungs offered in Canada.

Endobronchial ultrasound-guided bipolar radiofrequency ablation for lung cancer: A first-in-human clinical trial.

OBJECTIVE: Percutaneous radiofrequency ablation (RFA) is a therapeutic option for lung tumors. However, percutaneous approaches have limited access to central lung regions and a relatively high complication rate. To overcome these limitations, a needle-type bipolar RFA device compatible with an endobronchial ultrasound (EBUS) bronchoscope was developed. The aim of this pilot study was to evaluate the immediate-term safety and ablation zone of lung tumor EBUS-guided RFA. METHODS: This was an ablate-and-resect study in patients scheduled for surgical resection of clinical stage I or II lung cancer or metastatic lung lesions ≥1 cm that were accessible using an EBUS bronchoscope. The RFA electrodes were placed within the lung nodule using EBUS guidance followed by ablation. Bronchoscopy and contrast-enhanced computed tomography were performed to evaluate for post-RFA complications. The resected lung underwent pathological assessment to characterize the ablation zone. RESULTS: A total of 5 primary lung cancers were ablated in 5 separate patients; no patients with metastatic lesions were recruited. For a total energy of 4 kJ (n = 3), 6 kJ (n = 1), and 8 kJ (n = 1) delivered, the ablation time was a mean of 13.8 (range, 10.3-16.0) minutes, 8.4 minutes, and 15.6 minutes, respectively, and the maximum ablation diameter was a mean of 1.8 (range, 1.3-2.1) cm, 2.7 cm, and 2.6 cm, respectively. No immediate post-RFA complications were observed. CONCLUSIONS: EBUS-guided bipolar RFA can ablate lung tumors using real-time ultrasound guidance. EBUS-guided RFA might ultimately represent a minimally invasive therapy for lung cancer in patients unable to tolerate surgery. Longer-term safety will need to be evaluated.

Importance of tumor size in resectable stage III-N2 non-small cell lung cancer.

OBJECTIVE: The 8th TNM edition classifies stage III-N2 disease as IIIA and IIIB based on a tumor size cutoff of 5 cm. However, the importance of tumor size on survival in patients with resectable stage III-N2 disease has not been analyzed systematically. METHODS: Survival analysis based on tumor size (>5 cm vs ≤ 5 cm) for 255 consecutive patients with nonbulky (maximal lymph node diameter of 1.5 cm) stage III-N2 non-small cell lung cancer treated with surgery in our institution. RESULTS: Ninety patients (35.3%) underwent induction chemoradiation therapy (n = 72, 28%) or induction chemotherapy (n = 18, 7%), and 165 patients underwent primary surgery followed by adjuvant chemotherapy (n = 52, 32%), adjuvant chemoradiation therapy (n = 47, 29%), or adjuvant radiation therapy (n = 14, 13.2%). After a median follow-up of 6.5 years, the overall survival was 46.5% at 5 years and 28.9% at 10 years. In tumors 5 cm or less, there was no difference in survival between patients treated with induction or adjuvant therapy. However, in tumors greater than 5 cm, the survival was significantly better after induction therapy compared with adjuvant therapy or surgery alone. Pathologic multi-station N2 disease was more frequently detected in tumors greater than 5 cm (31% vs 18% in tumors ≤5 cm, P = .042), and the rate of R1 resection was lower after induction therapy (2.2% vs 8.5% in primary surgery, P = .048). CONCLUSIONS: These results support the redefinition of tumors greater than 5 cm with resectable N2 disease to stage IIIB. This change should help to refine the multimodality approach for stage III-N2 lung cancer.

Prognostic Significance of Pulmonary Multifocal Neuroendocrine Proliferation With Typical Carcinoid.

BACKGROUND: The clinical significance of multifocal pulmonary neuroendocrine proliferation (MNEP), including tumorlets and pulmonary neuroendocrine cell hyperplasia, in association with typical carcinoid (TC), is still debated. METHODS: We evaluated a retrospective series of TC with long-term follow-up data prospectively collected from 2 institutions and compared the outcome between TC alone and MNEP plus TC. Several baseline covariates were imbalanced between the MNEP plus TC and TC groups; therefore, we conducted 1:1 propensity score matching and inverse probability of treatment weighting in the full sample. In the matched group, the association of clinical, respiratory, and work-related factors with the group was determined through univariable and multivariable conditional logistic regression analysis. RESULTS: A total of 234 TC patients underwent surgery: 41 MNEP plus TC (17.5%) and 193 TC alone (82.5%). In the MNEP plus TC group, older age (P < .001), peripheral tumors (P = .0032), smaller tumor size (P = .011), and lymph node spread (P = .02) were observed compared with the TC group. Relapses occurred in 8 patients in the MNEP plus TC group (19.5%) and 7 in the TC group (3.6%). After matching, in 36 pairs of patients, a significantly higher 5-year progression-free rate was observed for the TC group (P < .01). Similar results were observed using inverse probability of treatment weighting in the full sample. The odds of being in the MNEP plus TC group was higher for those with work-related exposure to inhalant agents (P = .008), asthma or bronchitis (P = .002), emphysema, fibrosis, and inflammatory status (P = .032), or micronodules on the chest computed tomography scan and respiratory insufficiency (P = .036). CONCLUSIONS: The association with MNEP seems to represent a clinically and prognostic relevant factor in TC. Hence, careful preoperative workup, systematic pathologic evaluation, including nontumorous lung parenchyma, and long-term postoperative follow-up should be recommended in these patients.

Outcomes of patients with esophageal cancer after allogeneic hematopoietic stem cell transplantation.

Background: The improving survival in patients after allogeneic hematopoietic stem cell transplantation (aHCT) has warranted an increased attention to the long-term complications after aHCT especially second malignancies. The risk of developing esophageal cancer is thought to be higher than other malignancies after aHCT. There are limited data on the clinical characteristics, staging, treatment options and outcomes in these patients. Methods: We retrospectively reviewed all patients who underwent aHCT at our centre over 30 years and identified patients who developed secondary esophageal cancer. Patients were analyzed for transplant details, disease characteristics and therapy, relapse free survival (RFS), and overall survival (OS). Results: Ten patients [females 40% (n=4); median age 62 years] were diagnosed with esophageal cancer after a median duration of 5.8 years since aHCT. The standardized incidence ratio (SIR) for esophageal ca after aHCT was 1.96. Five patients (55.5%) had advanced clinical stages (stage III-IV) at diagnosis. Esophagectomy (with or without neoadjuvant chemotherapy) was performed in 50% (n=5) patients. Remission was achieved in 70% (n=7) of patients while 1 patient had progressive disease after planned treatment. Progressive disease was the cause in 50% (n=3) of deaths. Estimated 2- and 5-year overall survival after diagnosis of esophageal cancer was 60% and 45% respectively (median survival: 44.1 months). Conclusions: Despite the higher risk and increased incidence of esophageal cancer after aHCT, the outcomes these patients may be comparable to that in general population if diagnosed early. This implies the need for continued long term follow-up for patients after aHCT with a transplant physician.

Impact of donor time to cardiac arrest in lung donation after circulatory death.

OBJECTIVE: Acceptance of lungs from donation after circulatory determination of death has been generally restricted to donors who have cardiac arrest within 60 minutes after withdrawal of life-sustaining therapies. We aimed to determine the effect of the interval between withdrawal of life-sustaining therapies to arrest and recipient outcomes. Second, we aimed to compare outcomes between donation after circulatory determination of death transplants and donation after neurologic determination of death transplants. METHODS: A single-center, retrospective review was performed analyzing the clinical outcomes of transplant recipients who received donation after circulatory determination of death lungs and those who received donation after neurologic determination of death lungs. Donation after circulatory determination of death cases were then grouped on the basis of the interval between withdrawal of life-sustaining therapies and asystole: 0 to 19 minutes (rapid), 20 to 59 minutes (intermediate), and more than 60 minutes (long). Recipient outcomes from each of these groups were compared. RESULTS: A total of 180 cases of donation after circulatory determination of death and 1088 cases of donation after neurologic determination of death were reviewed between 2007 and 2017. There were no significant differences in the 2 groups in terms of age, gender, recipient diagnosis, and type of transplant (bilateral vs single). Ex vivo lung perfusion was used in 118 of 180 (65.6%) donation after circulatory determination of death cases and 149 of 1088 (13.7%) donation after neurologic determination of death cases before transplantation. The median survivals of recipients who received donation after circulatory determination of death lungs versus donation after neurologic determination of death lungs were 8.0 and 6.9 years, respectively. Time between withdrawal of life-sustaining therapies and asystole was available for 148 of 180 donors (82.2%) from the donation after circulatory determination of death group. Mean and median time from withdrawal of life-sustaining therapies to asystole were 28.6 minutes and 16 minutes, respectively. Twenty donors required more than 60 minutes to experience cardiac arrest, with the longest duration being 154 minutes before asystole was recorded. Recipients of donation after circulatory determination of death lungs who had cardiac arrest at 0 to 19 minutes (90 donors), 20 to 59 minutes (38 donors), and more than 60 minutes (20 donors) did not demonstrate any significant differences in terms of short- and long-term survivals, primary graft dysfunction 2 and 3, intensive care unit stay, mechanical ventilation days, or total hospital stay. CONCLUSIONS: Short- and long-term outcomes in recipients who received donation after neurologic determination of death versus donation after circulatory determination of death lungs are similar. Different withdrawals of life-sustaining therapies to arrest intervals were not associated with recipient outcomes. The maximum acceptable duration of this interval has yet to be established.

Deceased-donor lobar lung transplant: A successful strategy for small-sized recipients.

OBJECTIVES: Lobar lung transplantation (LLTx) from deceased donors is a potential solution for donor-recipient size mismatch for small sized recipients. We reviewed our institutional experience to compare outcomes after LLTx to standard lung transplantation (LTx). METHODS: We retrospectively reviewed transplants in our institution from January 2000 to December 2017. LLTx early- and long-term outcomes were compared with LTx. Additional analysis of outcomes was performed after dividing the cohort into 2 eras (era 1, 2000-2012; era 2, 2013-2017). RESULTS: Among the entire cohort (1665), 75 were LLTx (4.5%). Compared with LTx, LLTx were more frequently bridged to transplant with extracorporeal life support or mechanical ventilation and were transplanted in a rapidly deteriorating status (respectively, 20% vs 4.4%, P = .001; 22.7% vs 7.9, P < .001; and 41.3% vs 26.5%, P = .013). LLTx had longer intensive care unit and hospital lengths of stay (respectively, median 17 vs 4 days, and 45 vs 23, both P < .001), and greater 30-day mortality (13.3% vs 4.3%, P = .001) and 90-day mortality (17.3% vs 7.2%, P = .003). In era 2, despite a significantly greater 30-day mortality (10.8% vs 2.8%, P = .026), there was no significant difference in 90-day mortality between LLTx and LTx (13.5% vs 5.1%, P = .070). Overall survival at 1, 3, and 5 years was not significantly different between LLTx and LTx (73.2% vs 84.4%, 56.9% vs 68.4% and 50.4% vs 55.8, P = .088). CONCLUSIONS: Although LLTx is a high-risk procedure, both mid- and long-term survival are comparable with LTx in all cohorts in the modern era. LLTx therefore represents a valuable surgical option for small-sized recipients.

The impact of concordance with a lung cancer diagnosis pathway guideline on treatment access in patients with stage IV lung cancer.

BACKGROUND: Timely access to treatment of lung cancer is dependent on efficient and appropriate patient assessment and early referral for diagnostic workup. This study assesses the impact of Cancer Care Ontario (CCO) Lung Cancer Diagnostic Pathway Guideline (LCDPG) concordance on access to treatment of stage IV lung cancer patients referred to the Diagnostic Assessment Program (DAP) at a Canadian tertiary cancer centre. METHODS: This retrospective cohort study includes patients diagnosed with clinical stage IV lung cancer referred to the DAP at a Canadian tertiary cancer centre between November 1, 2015 and May 31, 2017. Referral concordance was determined based on CCO LCDPG. The primary outcome; time to treatment from initial healthcare presentation; was compared between the concordant and discordant referrals. RESULTS: Two hundred patients were referred for clinical stage IV lung cancer during the study period. Of these referrals, 151 (75.5%) were assessed and referred in concordance with LCDPG. Guideline concordant referrals were associated with reduced time to treatment from first healthcare presentation compared with guideline discordant referrals (55.3 vs. 108.8 days, P<0.001). Time to diagnostic procedure (32.2 vs. 86.7 days, P<0.001) and decision to treat (38.5 vs. 93.8 days, P<0.001) were also reduced with guideline concordance. The most common reason for discordant assessment and referral was delayed or inadequate investigation of symptoms in a high risk patient (32.7% of discordant referrals). CONCLUSIONS: Guideline concordant assessment and referral of stage IV lung cancer patients results in reduced time to diagnosis and treatment. Future research and education should focus on improving factors that delay DAP referral.

Nicotine dependence as a risk factor for upper aerodigestive tract (UADT) cancers: A mediation analysis.

PURPOSE: This study investigated nicotine dependence as an independent risk factor for upper aerodigestive tract (UADT) cancers, including lung and head and neck cancers (HNC). The study aimed to isolate the direct effect of nicotine dependence, independent of tobacco smoking. METHODS: A case-control study with a total of 4957 participants was conducted in Ontario, Canada, of which 2964 categorized as either current or former smokers were used in the analysis. Nicotine dependence of ever-smokers (2360 UADT cases and 604 controls) was measured using the Fagerström Test for Nicotine Dependence. Using mediation analyses and adjusted logistic regression models, we decomposed the direct effect of nicotine dependence and the mediated effect of smoking duration to quantify the risks of lung and HNC. The role of human papillomavirus (HPV) and cancer subtypes were assessed. RESULTS: Most individual nicotine dependence behaviours showed positive associations with lung cancer with approximately 1.8 to 3.5-fold risk increase, and to lesser extent with 1.4 to 2.3-fold risk for HNC. Nicotine dependence is partially accountable for increased risks of lung cancer (OR = 1.20, 95%CI = 1.13-1.28) and HNC (1.12, 95%CI = 1.04-1.19). Nicotine dependence had a greater effect on the risk of HPV-negative oropharyngeal cancer (OR = 3.06, 95%CI = 1.65-5.66) in comparison to HPV-positive oropharyngeal cancer (OR = 1.05, 95%CI = 0.67-1.65). The direct effects of nicotine dependence remained significant after accounting for cumulative tobacco exposures. CONCLUSION: Nicotine dependence increases the risks of lung and HNC cancers after accounting for tobacco smoking, suggesting potential toxic effects of nicotine. These results are informative for the safety consideration of nicotine exposures.

Postoperative but not intraoperative transfusions are associated with respiratory failure after pneumonectomy.

OBJECTIVES: Transfusion of blood products has been associated with increased risk of post-pneumonectomy respiratory failure. It is unclear whether intraoperative or postoperative transfusions confer a higher risk of respiratory failure. Our objective was to assess the role of transfusions in developing post-pneumonectomy respiratory failure. METHODS: We performed a retrospective cohort study using prospectively collected data on consecutive pneumonectomies between 2005 and 2015. Patient records were reviewed for intraoperative/postoperative exposures. Univariable and multivariable analyses were performed. RESULTS: Of the 251 pneumonectomies performed during the study period, 24 (9.6%) patients suffered respiratory failure. Ninety-day mortality was 5.6% (n = 14) and was more likely in patients with respiratory failure (7/24 vs 7/227, P < 0.001). Intraoperative and postoperative transfusions occurred in 42.2% (n = 106) and 44.6% (n = 112) of patients, respectively and were predominantly red blood cells. On univariable analysis, both intraoperative (P = 0.03) and postoperative transfusion (P = 0.004) were associated with a higher risk of respiratory failure. The multivariable model significantly predicted respiratory failure with an area under curve (AUC) = 0.88 (P = 0.001). On multivariable analysis, the only independent predictors of respiratory failure were postoperative transfusions [adjusted odds ratio (aOR) 6.54, 95% confidence interval (CI) 1.74-24.59; P = 0.005] and lower preoperative forced expiratory volume (adjusted OR 0.96, 95% CI 0.93-0.99; P = 0.03). Estimated blood loss was not significantly different (P = 0.91) between those with (median 800 ml, interquartile range 300-2000 ml) and without respiratory failure (median 800 ml, interquartile range 300-2000 ml). CONCLUSIONS: Respiratory failure occurred in 9.6% of patients post-pneumonectomy and confers a higher risk of 90-day mortality. Postoperative (but not intraoperative) transfusion was the strongest independent predictor associated with respiratory failure. Intraoperative transfusion may be in reaction to active/unpredictable blood loss and may not be easily modifiable. However, postoperative transfusion may be modifiable and potentially avoidable. Transfusion thresholds should be assessed in light of potential cost-benefit trade-offs.

Lung transplantation for cystic fibrosis.

BACKGROUND: The contribution of lung transplantation to the treatment of patients with end-stage cystic fibrosis (CF) has been debated. We aimed to describe achievable outcomes from high-volume CF and lung transplant programs. This study reports on the largest single-center experience of lung transplantation for adult and pediatric patients with CF. It also highlights the evolution of practice and outcomes over time. METHODS: A retrospective analysis of the prospectively collected Toronto Lung Transplant database was carried out. Post-transplant survival in CF was calculated using the Kaplan-Meier method and analyzed with log-rank tests. RESULTS: From 1983 to 2016, a total of 1,885 transplants were performed at our institution, where 364 (19.3%) were CF recipients and another 39 (2.1%) were CF retransplants. The mean age at first transplant was 29.5 ± 9.7 years where 56.6% were males and 91.5% were adults. Pre-transplantation, 88 patients (24.2%) were Burkholderia cepacia complex (BCC)-positive, 143 (39.3%) had diabetes mellitus, and the mean forced expiratory volume in one second was 26.0 ± 7.2%, as predicted at listing. The 1-, 5-, and 10-year probabilities of survival in adults who were BCC-negative were 94%, 70%, and 53%, respectively. Pediatric, BCC-positive, and retransplant recipients had worse survival than adult patients who were BCC-negative. Strategies to improve the donor pool did not affect survival but possibly reduced waitlist mortality. For the entire cohort, the most common causes of death after lung transplant were infection and chronic lung allograft dysfunction. CONCLUSIONS: Lung transplantation for CF provides excellent short- and long-term outcomes. These results strongly support lung transplantation as the standard of care for patients with CF having advanced lung disease.

Incidence of Ipsilateral Side Recurrence After Open or Video-Assisted Thoracic Surgery Resection of Colorectal Lung Metastases.

BACKGROUND: There is still controversy whether full lung palpation is required for patients undergoing pulmonary metastasectomy. We aimed to compare pulmonary ipsilateral recurrence (IR) after video-assisted thoracic surgery (VATS) or open surgery. METHODS: A retrospective study of all patients who underwent surgery for colorectal cancer lung metastases between 2003 and 2012 was performed. IR rate was compared between the 2 groups after adjusting for a propensity score matching based on age, sex, disease-free interval, number of metastases, type of resection, presence of a cardiovascular risk factor, presence of a respiratory risk factor, as well as the interaction between the number of metastases and the disease-free interval. The propensity score was used for matched and weighted comparisons of VATS and open patients. RESULTS: A total of 211 patients underwent surgery for colorectal cancer lung metastases. Of these, 75 (35.5%) were performed via VATS and 136 (64.5%) via open surgery. Before matching, 118 (55.9%) were male and the median age at the time of metastases diagnosis was 61 (range, 49.8-72.2) years. Median disease free-interval was 20 (19.7 ± 28.3) months; 22 (21.6 ± 28.5) months in VATS and 19 (19.0 ± 28.3) months in open surgery. In total, 19 (25.3%) developed IR in VATS, and 39 (28.7%) in open surgery. Five-year overall survival was 53.1% (61.9% VATS; 49.2% open). In the matched sample, IR was 23.6% in VATS vs 26.2% in open surgery (95% confidence interval for risk reduction with VATS: -22.6% to 17.5%; P = .80). CONCLUSIONS: No significant difference was observed in IR rates between VATS and open surgery in the treatment of colorectal cancer lung metastases.

Normothermic ex vivo lung perfusion: Does the indication impact organ utilization and patient outcomes after transplantation?

BACKGROUND: Ex vivo lung perfusion (EVLP) is being increasingly applied as a method to evaluate and treat donor lungs for transplantation. However, with the previous limited worldwide experience, no studies have been able to evaluate the impact of indication for EVLP on organ utilization rates and recipient outcomes after lung transplantation (LTx). We examined these outcomes in a large-cohort, single-center series of clinical EVLP cases. METHODS: All EVLP procedures performed at our institution between October 2008 and December 2017 were examined. The EVLPs were divided into 4 groups based on the indication for the procedure: group 1, high-risk brain death donors (HR-BDD); group 2, standard-risk donation after cardiac death (S-DCD); group 3, high-risk donation after cardiac death (HR-DCD); and group 4, logistics (LOGISTICS, the need for prolongation of preservation time or organ retrieval by a different transplantation team). RESULTS: During the study period, a total of 1106 lung transplants were performed in our institution. In this period, 372 EVLPs were performed, 255 (69%) of which were accepted for transplantation, resulting in 262 transplants. Utilization rates were 70% (140 of 198) for group 1, 82% (40 of 49) for group 2, 63% (69 of 109) for group 3, and 81% (13 of 16) for group 4 (P = .42, Fisher's exact test). Recipient age (P = .27) and medical diagnosis (P = .31) were not different across the 4 groups. Kaplan-Meier survival by EVLP indication group demonstrated no differences. Thirty-day mortality was 2.1% in group 1, 5% in group 2, 2.9% in group 3, and 0% in group 4 (P = .87, Fisher's exact test). The median days of mechanical ventilation, intensive care unit stay, and hospital stay were 2, 4, and 21 in group 1; 2, 3, and 21 in group 2; 3, 5, and 28 in group 3; and 2, 4, and 17 in group 4 (P = .29, .17, and .09, respectively, Kruskal-Wallis rank-sum test). CONCLUSIONS: Clinical implementation of EVLP has allowed our program to expand the annual lung transplantation activity by 70% in this time period. It has improved confidence in the utilization of DCD lungs and BDD lungs, with an average 70% utilization of post-EVLP treated donor lungs with excellent outcomes, while addressing significant challenges in donor lung assessment and the logistics of "real-life" clinical lung transplantation.