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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Thoracic surgery is associated with one of the highest rates of chronic postsurgical pain (CPSP) among all surgical subtypes. Chronic postsurgical pain carries significant medical, psychological, and economic consequences, and further interventions are needed to prevent its development. This study aimed to determine the prevalence, characteristics, and risk factors associated with CPSP after thoracic surgery. A prospective cohort study. Single-center tertiary care hospital. This study included 285 adult patients who underwent thoracic surgery at Toronto General Hospital in Toronto, Canada, between 2012 and 2020. Demographic, psychological, and clinical data were collected perioperatively, and follow-up evaluations were administered at 3, 6, and 12 months after surgery to assess CPSP. Chronic postsurgical pain was reported in 32.4%, 25.4%, and 18.2% of patients at 3, 6, and 12 months postoperatively, respectively. Average CPSP pain intensity was rated to be 3.37 (SD 1.82) at 3 months. Features of neuropathic pain were present in 48.7% of patients with CPSP at 3 months and 71% at 1 year. Multivariate logistic regression models indicated that independent predictors for CPSP at 3 months were scores on the Hospital Anxiety and Depression Scale (adjusted odds ratio [aOR] of 1.07, 95% CI of 1.02 to 1.14, p = 0.012) and acute postoperative pain (aOR of 2.75, 95% CI of 1.19 to 6.36, p = 0.018). None. Approximately 1 in 3 patients will continue to have pain at 3 months after surgery, with a large proportion reporting neuropathic features. Risk factors for pain at 3 months may include preoperative anxiety and depression and acute postoperative pain. [ABSTRACT FROM AUTHOR]

The use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation. The AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement. The expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively. Achieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation. [ABSTRACT FROM AUTHOR]

A paucity of data supports the use of transesophageal echocardiography (TEE) for bedside extracorporeal membrane oxygenation (ECMO) cannulation. Concerns have been raised about performing TEEs in patients with COVID-19. The authors describe the use and safety of TEE guidance for ECMO cannulation for COVID-19. Single-center retrospective cohort study. The study took place in the intensive care unit of an academic tertiary center. The authors included 107 patients with confirmed SARS-CoV-2 infection who underwent bedside venovenous ECMO (VV ECMO) cannulation under TEE guidance between May 2020 and June 2021. TEE-guided bedside VV ECMO cannulation. Patient characteristics, physiologic and ventilatory parameters, and echocardiographic findings were analyzed. The primary outcome was the number of successful TEE-guided bedside cannulations without complications. The secondary outcomes were cannulation complications, frequency of cannula repositioning, and TEE-related complications. TEE-guided cannulation was successful in 99% of the patients. Initial cannula position was adequate in all but 1 patient. Fourteen patients (13%) required cannula repositioning during ECMO support. Forty-five patients (42%) had right ventricular systolic dysfunction, and 9 (8%) had left ventricular systolic dysfunction. Twelve patients (11%) had intracardiac thrombi. One superficial arterial injury and 1 pneumothorax occurred. No pericardial tamponade, hemothorax or intraabdominal bleeding occurred in the authors' cohort. No TEE-related complications or COVID-19 infection of healthcare providers were reported during this study. Bedside TEE guidance for VV ECMO cannulation is safe in patients with severe respiratory failure due to COVID-19. No tamponade or hemothorax, nor TEE-related complications were observed in the authors' cohort. [ABSTRACT FROM AUTHOR]

Ex vivo lung perfusion (EVLP) is an excellent platform to evaluate donor lung function before transplantation, but novel methods are needed to accurately confirm transplant quality. Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) has been used in various clinical perioperative applications to evaluate tissue perfusion. We used NIRF imaging during pig and human EVLP to evaluate donor lung perfusion and edema. Pig lungs with various degrees of lung injury (n = 10) and human lungs rejected from clinical transplantation (n = 3) were imaged during EVLP using intravascular ICG and a SPY Elite (Stryker) NIRF imaging unit. Optimal ICG and imaging conditions, and perfusion and edema quantification methods, were established. Pig lung transplants with extended graft preservation (n = 5) and control native lungs (n = 6) were also imaged. A single ICG dose resulted in sustained donor lung NIRF throughout the EVLP. Even and homogenous ICG signal was demonstrated in areas of normal lung. Low NIRF was present in regions with poor tissue perfusion, and rapid, intense ICG accumulation occurred in damaged and edematous areas. Segmental perfusion defects were common in the peripheral and elevated regions of the lungs, and serial imaging showed gradual perfusion recovery during EVLP. Impaired microvascular reperfusion, indicated by a decreased NIRF ingress rate, was detected in transplanted pig lungs early after reperfusion. NIRF imaging enables noninvasive real-time evaluation of lung perfusion and edema during EVLP. Prospective clinical studies are needed to determine the role of NIRF imaging in donor lung assessment and selection, and prediction of posttransplant outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. The study's methods, results, and implications. [Display omitted] [ABSTRACT FROM AUTHOR]

Lobar lung transplant is a technique that allows for large-sized donor lungs to be implanted into small-sized adult and pediatric recipients. Often, these recipients have longer waiting list times due to a shortage of appropriately sized donors, with the potential for increased waiting list mortality. Lobar lung transplant involves implanting a single lobe from each lung instead of the usual full-lung implant, thus ameliorating the size difference between donor and recipient. The first important step in this procedure involves proper donor-recipient size-matching, using calculation of total lung capacity using the bronchopulmonary segments to choose the appropriate lobes for the recipient. The preferred lobes to use are the lower lobes (or right lower lobe and right middle lobe, depending on sizing) as they are usually larger lobes and have a larger vascular bed. The surgery should ideally be done at experienced centers with high volume thoracic surgery where surgeons are very familiar with the pulmonary anatomy. Once the lungs are split, careful dissection is performed in order to ensure that the cuffs on the vein, artery and bronchus of the lobe to be used are of adequate length and undamaged during the dissection. The implantation must be performed on cardio-pulmonary support (preferably venoarterial extracorporeal membrane oxygenation) in order protect the lobes during the periods of reperfusion. [ABSTRACT FROM AUTHOR]

Ex vivo lung perfusion provides an innovative method to assess and repair donor lungs. The current Toronto ex vivo lung perfusion protocol can reliably and reproducibly preserve lungs for 12 hours. A longer ex vivo lung perfusion preservation time could enable the application of more advanced repair therapies and the rescue of more donor lungs for lung transplant. Our objective was to achieve stable 24-hour normothermic ex vivo lung perfusion. We systematically examined 3 modifications of ex vivo lung perfusion perfusate administration in a large animal 24-hour ex vivo lung perfusion model. Pig lungs were assigned to 4 groups (n = 5 per group): (1) control; (2) continuous replacement of ex vivo lung perfusion perfusate; (3) modified feed, which used a modified solution to maintain perfusate osmolality by adjusting glucose and sodium levels; and (4) total parenteral nutrition, in which we added parenteral nutrition to the perfusate. Only 1 lung in the control group completed 24-hour ex vivo lung perfusion. However, 24-hour perfusion was achieved in 4 lungs in the continuous replacement group, 3 lungs in the modified feed group, and 4 lungs in the total parenteral nutrition group. The total parenteral nutrition group achieved significantly longer stable perfusion time compared with control (P =.03). Lung function was significantly improved and inflammatory cytokine production was reduced in the continuous replacement and total parenteral nutrition groups compared with control. Modifications of ex vivo lung perfusion perfusate toward achieving a stable homeostatic state can extend perfusion time for up to 24 hours. Although these modifications allow for prolonged ex vivo lung perfusion, further research will be required to develop stable lung support beyond 24 hours. Three modifications of EVLP perfusate administration in a pig 24-hour EVLP model. The TPN group achieved significantly longer stable perfusion time compared with control (P =.03). The dotted lines represent 95% confidence interval. [Display omitted] [ABSTRACT FROM AUTHOR]

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). 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). 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). 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. Lobar lung transplant should be considered a valid option for pediatric and small-sized recipients, as they have longer times on the waiting list. Survival has improved in the modern era, with equivalent 90-day and long-term survival when compared with standard bilateral lung transplant. [Display omitted] [ABSTRACT FROM AUTHOR]

To determine the dose-limiting toxicity of oxaliplatin chemotherapy delivered by in vivo lung perfusion (IVLP). To allow assessment of subacute toxicities, we aimed to develop a 72-hour porcine IVLP survival model. In total, 12 Yorkshire male pigs were used. Left lung IVLP was performed for 3 hours. At 72 hours postoperatively, computed tomography imaging of the lungs was performed before the pigs were killed. Lung physiology, airway dynamics, gross appearance, and histology were assessed before and during IVLP, at reperfusion, and when the pigs were euthanized. An accelerated titration dose-escalation study design was employed whereby oxaliplatin doses were sequentially doubled provided no clinically significant toxicity was observed, defined as an arterial partial pressure of oxygen to fraction of inspired oxygen ratio <300 mm Hg or severe acute lung injury on biopsy. After an initial training phase, no mortality or adverse events related to the procedure were observed. There was no lung injury observed at the time of IVLP for any case. At sacrifice, clinically significant lung injury was observed at 80 mg/L oxaliplatin, with an arterial partial pressure of oxygen to fraction of inspired oxygen ratio of 112 mm Hg. Mild and subclinical lung injury was observed at 40 mg/L, with this dose being repeated to confirm safety. A stable and reproducible porcine 3-day IVLP survival model was established that will allow toxicity assessment of agents delivered by IVLP. Oxaliplatin delivered by IVLP showed delayed-onset toxicity that was not apparent at the time of reperfusion, with a maximal-tolerated dose of 40 mg/L. This information will inform initiation of a clinical trial examining IVLP delivery of oxaliplatin at our institution. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Diagnosing lung injury is a challenge in lung transplantation. It has been unclear if a single biopsy specimen is truly representative of the entire organ. Our objective was to investigate lung inflammatory biomarkers using human lung tissue biopsies and ex vivo lung perfusion perfusate. Eight human donor lungs declined for transplantation were air inflated, flash frozen, and partitioned from apex to base. Biopsies were then sampled throughout the lung. Perfusate was sampled from 4 lung lobes in 8 additional donor lungs subjected to ex vivo lung perfusion. The levels of interleukin-6, interleukin-8, interleukin-10, and interleukin-1β were measured using quantitative reverse transcription polymerase chain reaction from lung biopsies and enzyme-linked immunosorbent assay from ex vivo lung perfusion perfusate. The median intra-biopsy equal-variance P value was.50 for messenger RNA biomarkers in tissue biopsies. The median intra-biopsy coefficient of variance was 18%. In donors with no apparent focal injuries, the biopsies in each donor showed no difference in various lung slices, with a coefficient of variance of 20%. The exception was biopsies from the lingula and injured focal areas that demonstrated larger differences. Cytokines in ex vivo lung perfusion perfusate showed minimal variation among different lobes (coefficient of variance = 4.9%). Cytokine gene expression in lung biopsies was consistent, and the biopsy analysis reflects the whole lung, except when specimens were collected from the lingula or an area of focal injury. Ex vivo lung perfusion perfusate also provides a representative measurement of lung inflammation from the draining lobe. These results will reassure clinicians that a lung biopsy or an ex vivo lung perfusion perfusate sample can be used to inform donor lung selection. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Objectives The purpose of this study was to determine the frequency, characteristics, and survival of second primary lung cancer initially identified as an indeterminate lesion on the original computed tomography scan and then diagnosed during the surveillance period in a prospective study. Methods A prospective database of 271 patients enrolled in a surveillance study was updated. Indeterminate lesions present on the original computed tomography at the time of initial primary lung cancer diagnosis that subsequently grew and were diagnosed as cancer were termed "synchronous primary lung cancer." Lesions that were not present on the original computed tomography scan and subsequently diagnosed on surveillance were termed "metachronous primary lung cancer." Results Thirty patients (11.1%) developed 37 second primary lung cancers over a median surveillance period of 84.7 (range, 15.9-147.6) months. Of these, 15 of 37 (40.5%) were identified as synchronous primary lung cancer, and 22 of 37 (59.5%) were identified as metachronous primary lung cancer. At first identification, ground-glass lesions were identified in 9 of 15 (60%) synchronous primary lung cancers compared with only 5 of 22 (22.7%) of metachronous primary lung cancers (P =.034). Compared with metachronous primary lung cancer, from first identification to diagnosis, synchronous primary lung cancer developed over a longer interval (33.6 vs 7.2 months, P =.001) and had a slower growth rate (0.17 vs 0.45 mm/month, P =.027). The 5-year overall survival from second lung cancer was 73.0%. No significant differences were observed between the synchronous primary lung cancer and metachronous primary lung cancer cohorts in overall survival from initial primary lung cancer (P =.583) or from second lung cancer (P =.966). Conclusions Computed tomography surveillance identifies 2 types of curable second lung cancers leading to excellent overall survival. [ABSTRACT FROM AUTHOR]

Background The study aim is to compare the diagnostic yield, safety, and cost of outpatient awake thoracoscopy (AT) with video-assisted thoracoscopic surgery (VATS) pleural biopsy in undiagnosed pleural effusions. Methods The diagnostic yield of pleural biopsy performed by AT or VATS in patients with undiagnosed exudative pleural effusions at a tertiary thoracic surgery center in Canada between 2011 and 2015 was retrospectively evaluated. Test sensitivity, specificity, positive predictive value, and negative predictive value were compared. Procedure safety, hospital length of stay, additional pleural-based interventions, and procedure-related costs were compared. Results Patients underwent either AT (n = 78) or VATS (n = 99) during the study period. Sensitivity, specificity, positive predictive value, and negative predictive value were 85%, 100%, 100%, and 79% for AT and 93%, 94%, 99%, and 76% for VATS, with no significant difference in diagnostic test performance. There was no difference in the rate of major complications (2 AT [2.6%] versus 4 VATS [4.0%], p = 0.696), minor complications (14 AT [17.9%] versus 16 VATS [16.2%], p = 0.841) or need for additional pleural-based procedures (20 AT [25.6%] versus 18 VATS [18.2%], p = 0.270). The VATS was associated with longer median hospital stay (VATS 3 days [interquartile range: 1 to 4] versus AT 0 days [interquartile range: 0 to 1], z = 6.98, p < 0.001) and a higher procedure-related average cost (VATS Canadian dollars $7,962 [95% confidence interval: $7,134 to $8,790] versus AT Canadian dollars $2,815 [95% confidence interval: $2,010 to $3,620], p < 0.001). Conclusions Awake thoracoscopy and VATS have similar diagnostic yield and safety profiles in the assessment of undiagnosed pleural effusions; however, AT is associated with shorter length of stay and lower average per-procedure cost. In the appropriate clinical setting, AT may be the diagnostic test of choice. [ABSTRACT FROM AUTHOR]

Objectives Localization and resection of nonvisible, nonpalpable pulmonary nodules during video-assisted thoracoscopic surgery are challenging. Our study was to determine the feasibility and safety of indocyanine green fluorescence localization and resection of small nodules using a near-infrared fluorescence thoracoscope. Methods Twenty patients with undiagnosed peripheral nodules smaller than 3 cm scheduled for computed tomography–guided microcoil placement followed by video-assisted thoracoscopic surgery wedge resection were enrolled. After microcoil deployment, 100 to 150 μL of diluted indocyanine green was injected percutaneously near the nodule. The nodule initially was localized solely by using a near-infrared thoracoscope to visualize indocyanine green fluorescence. Thoracoscopic instruments were used to determine the staple line. Wedge resection was performed after confirmation of the location of the microcoil using fluoroscopy. Results Twenty patients underwent near-infrared, image-guided, video-assisted thoracoscopic surgery resection. The median computed tomography tumor size was 1.2 cm. The median depth from the pleural surface was 1.4 cm (range, 0.2-4.8 cm). The median computed tomography–guided intervention time was 35 minutes, and video-assisted thoracoscopic surgery procedural time was 54 minutes. Indocyanine green fluorescence was clearly identified in 18 of 20 patients (90%). The surgical margins were all negative on final pathology without the need for additional resection. The final diagnoses included 18 primary lung cancers, 1 metastatic lung cancer, and 1 benign lung tumor. Conclusions Computed tomography–guided percutaneous indocyanine green injection and intraoperative near-infrared localization of small nodules are safe and feasible. These offer surgeons the ease of localization through direct indocyanine green fluorescence imaging without the use of fluoroscopy and may be a complementary technique to preoperative microcoil placement for nonvisible, nonpalpable intrapulmonary nodules. [ABSTRACT FROM AUTHOR]

Objective To assess the cost-effectiveness of various modes of mediastinal staging in non–small cell lung cancer (NSCLC) in a single-payer health care system. Methods We performed a decision analysis to compare the health outcomes and costs of 4 mediastinal staging strategies: no invasive staging, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), mediastinoscopy, and EBUS-TBNA followed by mediastinoscopy if EBUS-TBNA is negative. We determined incremental cost effectiveness ratios (ICER) for all strategies and performed comprehensive deterministic sensitivity analyses using a willingness to pay threshold of $80,000/quality adjusted life year (QALY). Results Under the base-case scenario, the no invasive mediastinal staging strategy was least effective (QALY, 5.80) and least expensive ($11,863), followed by mediastinoscopy, EBUS-TBNA, and EBUS-TBNA followed by mediastinoscopy with 5.86, 5.87, and 5.88 QALYs, respectively. The ICER was ∼$26,000/QALY for EBUS-TBNA staging and ∼$1,400,000/QALY for EBUS-TBNA followed by mediastinoscopy. The mediastinoscopy strategy was dominated. Once pN2 exceeds 2.5%, EBUS-TBNA staging is cost-effective (∼$80,000/QALY). Once the pN2 reaches 57%, EBUS-TBNA followed by mediastinoscopy is cost-effective (ICER ∼$79,000/QALY). Once EBUS-TBNA sensitivity exceeds 25%, EBUS-TBNA staging is cost-effective (ICER ∼$79,000/QALY). Once pN2 exceeds 25%, confirmatory mediastinoscopy should be added, in cases of EBUS-TBNA sensitivity ≤ 60%. Conclusions Invasive mediastinal staging in NSCLC is unlikely to be cost-effective in clinical N0 patients if pN2 <2.5%. In patients with probability of mediastinal metastasis between 2.5% and 57% EBUS-TBNA is cost-effective as the only staging modality. Confirmatory mediastinoscopy should be considered in high-risk patients (pN2 > 57%) in case of negative EBUS-TBNA. [ABSTRACT FROM AUTHOR]

Background Despite guidelines for preoperative invasive mediastinal staging (IMS) for non-small cell lung cancer (NSCLC), concordance with guidelines and whether the use of these guidelines results in expected frequency of lymph node metastases has not been evaluated. Our objectives were to determine guideline concordance, reasons for nonconcordance, and, in patients who did not receive IMS, to determine the use of operative nodal sampling and final pathologic staging. Methods Patients who had a resection for NSCLC between 2010 and 2012 were identified from the Institutional Cancer Registry. A chart audit was performed to determine adherence to Cancer Care Ontario (CCO) IMS guideline criteria, and pathologic reports were reviewed to determine postresection staging. Results Of 242 resections performed in the study period 102 (42%) did not receive IMS. 66 patients (65%) did not require IMS based on CCO guidelines and thus were concordant with guidelines, whereas 36 (36%) were guideline nonconcordant. Of 102 patients who did not have preoperative IMS, only 72 had intraoperative lymph node assessment and only 35 (34%) had sampling of three or more ipsilateral (N2) nodal stations. In the guideline concordant group, 2 of 66 patients (5%) had positive N2 nodes, whereas in the nonconcordant group 3 of 36 patients (11%) were N2 positive. Conclusions Although overall IMS was used in only 140 patients (58%), concordance with guidelines was high at 85% (206 of 242 patients). However, rates of intraoperative nodal sampling for non-IMS cases (both concordant and nonconcordant) was lower than expected, resulting in potentially understaged patients. [ABSTRACT FROM AUTHOR]

Background Pulmonary lobectomy is the standard of care for resection of non-small cell lung cancer (NSCLC). Patients with compromised lung function who are considered high risk may be denied surgical treatment; thus, proper identification of those truly at high risk is critical. Video-assisted thoracic surgery (VATS) may reduce the operative risk. This study reviews our institutional experience of pulmonary lobectomy by open thoracotomy or VATS techniques in patients deemed to be high risk. Methods A retrospective review of an institutional database was performed for all patients undergoing lobectomy from 2002 to 2010. Patients were grouped into high-risk (HR) and standard-risk (SR) cohorts according to the American College of Surgeons Oncology Group Z4099/Radiation Therapy Oncology Group 1021 criteria. Results From 2002 to 2010, 72 HR and 536 SR patients underwent lobectomy. Mean age was 73 years for HR and 66 years for SR ( p < 0.0001). Rates of overall ( p < 0.0001) and pulmonary complications ( p < 0.0001) were significantly higher in the HR group. However, when HR patients were resected by VATS, there was no significant difference in overall ( p = 0.1299) or pulmonary complications ( p = 0.2292) compared with the SR VATS group. Moreover, overall survival was significantly lower for HR patients who had an open operation compared with VATS lobectomy or SR open ( p = 0.0028). Conclusions VATS lobectomy offers patients who are considered to be at increased risk for open lobectomy a feasible procedure, with no difference in overall survival compared with SR patients, and decreased morbidity compared with open lobectomy. VATS lobectomy should be considered for patients who historically may not have been considered for surgical resection. [ABSTRACT FROM AUTHOR]

Background Sevoflurane is one of the most commonly used volatile anesthetic agents with the fastest onset and offset, replacing isoflurane in modern anesthesiology. Preconditioning and postconditioning using volatile anesthetics can attenuate ischemia-reperfusion injury (IRI). However, no previous studies have evaluated the effect of sevoflurane in lung transplantation after cold ischemic injury. We aimed to study the effects of donor and recipient treatment with sevoflurane in a rat lung transplantation model. Methods Lewis rats were allocated to four groups: control, PreC (preconditioning), PostC (postconditioning), and PreC + PostC. Donor rats in the PreC and PreC + PostC groups were exposed to 1.5% sevoflurane for 30 minutes before donor operation. Donor lungs were flushed with Perfadex and stored for 12 hours at 4°C before transplantation. Recipients received orthotopic left lung transplantation. In the PostC and PreC + PostC groups, sevoflurane was initiated 2 minutes before reperfusion and maintained for 30 minutes. Two hours after reperfusion, lung function was evaluated, and samples were collected for histologic, inflammatory, and cell death assessment. Results Preconditioning and postconditioning using sevoflurane significantly improved the oxygenation of lung grafts (partial arterial gas pressure of oxygen: 198 mm Hg in control, 406.5 mm Hg in PreC, 472.4 mm Hg in PostC, and 409.7 mm Hg in PreC + PostC, p < 0.0001) and reduced pulmonary edema. Sevoflurane treatment reduced levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Moreover, sevoflurane significantly inhibited apoptotic cells by a decrease in cytochrome c release into cytosol and caspase-3 cleavage. Conclusions Preconditioning or postconditioning of lungs using sevoflurane exhibits a significant protective effect against early phase of ischemia-reperfusion injury in a rat lung transplantation model. [ABSTRACT FROM AUTHOR]

Background Localization of small, nonvisible and nonpalpable nodules is challenging during video-assisted thoracoscopic surgery. We evaluated the feasibility of using a new ultrasound thoracoscope to localize nodules in resected ex vivo human lungs. Methods The tumor was localized and measured in its greatest dimension with a prototype ultrasound thoracoscope (XLTF-UC180; Olympus Corporation, Tokyo, Japan) at different frequencies (5.0 to 12.0 MHz) and different lung specimen states (deflated, semiinflated). Measured tumor size and depth from lung surface were compared and correlated to the true diameter and depth from lung surface acquired from pathologic morphology. Results Ex vivo evaluation was performed on 16 solid nodules and nine part solid ground-glass nodules. All tumors were successfully localized in the deflated lung specimens (average size, 13.7 ± 5.2 mm). The tumor boundaries were best evaluated with an ultrasound frequency of 10 MHz. Solid nodules were more easily visualized than ground-glass nodules. Part solid ground-glass nodules were not easily detected in the semiinflated specimen owing to peritumoral air surrounding the tumor. Tumor boundaries were also difficult to identify in deeply situated tumors and in lungs with underlying disease. A strong positive correlation existed between the ultrasound measurement and true measurement of tumor size ( R 2 = 0.89, p < 0.001). Conclusions The ultrasound thoracoscope can be used to localize nodules in resected human lungs. The clarity of the tumor boundaries is influenced by the tumor type and depth and the underlying pulmonary disease. Complete lung deflation and the use of 10 MHz ultrasound frequency optimize the visualization of target tumors. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. Graphical abstract summarizing methods and main findings of the study. [Display omitted] [ABSTRACT FROM AUTHOR]

Isolated lung metastases in sarcoma and colorectal cancer patients are inadequately treated with current standard therapies. In Vivo Lung Perfusion, a novel platform, could overcome limitations to photodynamic therapy treatment volumes by using low cellular perfusate, removing blood, and thus allowing greater light penetration. Development of personalized photodynamic therapy protocols requires in silico light propagation simulations based on optical properties and maximal permissible photodynamic threshold doses of lung tissue. This approach aims to maximize the effective treatment dose to the lung while avoiding toxicity to healthy lung tissue. Based on this rationale, the overall objective of this study is to create a whole-lung perfusion assisted PDT protocol. Specifically, we aimed to develop a light delivery system to deliver light homogenously to the entire lung and validate simulations of light distribution in the organ to guide personalized PDT dosimetry. Using a porcine model, animals underwent a modified lung flush procedure to remove blood from the organ. Our light delivery system comprised of multiple LED cylindrical panels emitting 660nm light were placed within the lung cavity, while isotropic detectors were placed within bronchoscopically within various lung segments via the airways. Local fluence rates were collected from fibers. A CT scan was performed using optical phantoms in place of sources, and an in silico model of the lung was generated based on segmentation of the scans (Figure 1). Light propagation in the lung was modelled using the FullMonte simulator inputting our previously determined optical properties at 660nm as parameters. Fluence rate attenuation curves were created from simulations of each experiment plotting the fluence rate over the relative distance from sources (Figure 2A). These curves were used to calculate the effective attenuation coefficient for each model based on our previously determined lung optical properties. Comparison of the irradiance and effective attenuation coefficients calculated from the model and direct measurements taken during experiments are shown in Figure 2B. Overall, there was strong reliability of our simulation thus validating the in silico model. This model will be used to guide personalized dosimetry of PDT treatments by informing the number, position, and intensity of light sources to achieve a desired fluence range within the lung parenchyma. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

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. 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. 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) 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Ex vivo lung perfusion (EVLP) allows for the evaluation and treatment of donor lungs before transplant. Different EVLP strategies have been described using either an open left atrium (LA) (pressure of 0 mm Hg) or closed LA (pressure of 5 mm Hg). We hypothesized that maintaining a physiologic positive LA pressure during EVLP is protective to the lung. Methods Pig lungs were flushed with Perfadex, retrieved and stored at 4°C for 4 hours [short cold ischemic time (CIT), n = 10] or 18 hours (prolonged CIT, n = 8). Subsequently, lungs underwent normothermic EVLP for 12 hours using either an open or closed LA technique. A linear mixed effect model was used to compare functional parameters between the 2 groups. Results After short CIT, 12-hour EVLP could not be completed in 4 of 5 open atrium cases due to significant pulmonary edema. Lung injury was evident in this group after 7 hours of EVLP, demonstrating an increase in pulmonary vascular resistance ( p < 0.001) and peak inspiratory pressure ( p = 0.001), and a decrease in lung compliance ( p < 0.001) and perfusate oxygenation ( p = 0.04). In contrast, in the closed atrium group, all lungs completed 12 hours of EVLP with stable functional parameters. At the end of the experiment, the wet/dry ratio ( p = 0.015) and lung edema score ( p = 0.02) were significantly worse in the open LA group compared with the closed LA EVLP group. Similar findings were observed in the prolonged CIT group. Conclusion The use of a closed atrial technique to create a controlled positive LA during EVLP leads to significantly less edema and superior lung physiology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective We hypothesized that administration of a homodimer of recombinant annexin V, diannexin, could shield phosphatidylserine on the endothelium, and inhibit leukocyte and platelet adhesion, thereby potentially reducing ischemia reperfusion injury (IRI) in lung transplantation. This hypothesis was tested using a rat syngeneic single left-lung transplant model. Methods Rats were randomly assigned to receive diannexin (DN group; n = 10) or normal saline (control group; n = 10). Diannexin (1000 μg/kg) was administered to the donor lung in the pulmonary flush solution, and to the recipient intravenously, 5 minutes after initiation of reperfusion. Grafts were reperfused for 2 hours. Results The transplanted grafts in the DN group performed significantly better in gas exchange with higher partial pressure of oxygen (control group: 179 ± 121 vs DN group: 330 ± 54 mm Hg; P = .007) and lower partial pressure of carbon dioxide (control: 55.1 ± 26 vs DN: 34.2 ± 11 mm Hg; P = .04), as well as lower peak airway pressure (control: 20.5 ± 8.5 vs DN: 12.0 ± 7.9 cm H 2 O; P = .035) after 2 hours of reperfusion. Wet-to-dry lung weight ratio ( P = .054), and alveolar fibrin deposition score ( P = .04), were reduced in the DN group. Caspase-cleaved cytokeratin 18 in plasma (a marker of epithelial apoptosis) was significantly reduced in the DN group ( P = .013). Furthermore, gene-expression levels of proinflammatory cytokines in the transplanted graft, including interleukin-6 ( P = .04) and macrophage inflammatory protein 2 ( P = .03) were significantly decreased in the DN group. Conclusions A homodimer of recombinant annexin V reduced ischemia reperfusion injury in a lung transplant animal model, by reducing cell death and tissue inflammation. [ABSTRACT FROM AUTHOR]