Intersurgeon variations in postoperative length of stay after video-assisted thoracoscopic surgery lobectomy.

Objectives: To identify factors associated with prolonged postoperative length of stay (LOS) after VATS lobectomy (VATS-L), explore potential intersurgeon variation in LOS and ascertain whether or not early discharge influences hospital readmission rates. Methods: We conducted a retrospective analysis of patients who underwent VATS-L at a single academic center between 2018 and 2021. Each VATS lobectomy procedure was performed by 1 of 7 experienced thoracic surgeons. The primary end point of interest was prolonged LOS, defined as an index LOS >3 days. Results: Among 1006 patients who underwent VATS lobectomy, 632 (63%) had a prolonged LOS. On multivariate analysis, the factors independently associated with prolonged LOS were: surgeon (P < .001), patient age (odds ratio [OR], 1.03; 95% CI, 1.02-1.06), operation time (OR, 1.01; 95% CI, 1.01-1.01), postoperative complication (OR, 3.60; 95% CI, 2.45-5.29), and prolonged air leak (OR, 8.95; 95% CI, 4.17-19.23). There was no significant association between LOS and gender, body mass index, coronary artery disease, prior atrial fibrillation, American Society of Anesthesiologists score >3, and prior ipsilateral thoracic surgery or sternotomy. There was no association between LOS ≤3 days and hospital readmission (20 [5.3%] vs 39 [5.9%]; OR, 0.88; 95% CI, 0.50-1.53). Conclusions: An intersurgeon variation in postoperative LOS after VATS-L exists and is independent of patient baseline characteristics or perioperative complications. This variation seems to be more closely related to differences in postoperative management and discharge practices rather than to surgical quality. Postoperative discharge within 3 days is safe and does not increase hospital readmissions.

Right Ventricular Assist Device With an Oxygenator for the Management of Combined Right Ventricular and Respiratory Failure: A Systematic Review.

BACKGROUND: Severe lung disease frequently presents with both refractory hypoxemia and right ventricular (RV) failure. Right ventricular assist device with an oxygenator (OxyRVAD) is an extracorporeal membrane oxygenation (ECMO) configuration of RV bypass that also supplements gas exchange. This systematic review summarises the available literature regarding the use of OxyRVAD in the setting of severe lung disease with associated RV failure. METHODS: PubMed, Embase, and Google Scholar were queried on September 27, 2023, for articles describing the use of an OxyRVAD configuration. The main outcome of interest was survival to intensive care unit (ICU) discharge. Data on the duration of OxyRVAD support and device-related complications were also recorded. RESULTS: Out of 475 identified articles, 33 were retained for analysis. Twenty-one articles were case reports, and 12 were case series, representing a total of 103 patients. No article provided a comparison group. Most patients (76.4%) were moved to OxyRVAD from another type of mechanical support. OxyRVAD was used as a bridge to transplant or curative surgery in 37.4% and as a bridge to recovery or decision in 62.6%. Thirty-one patients (30.1%) were managed with the dedicated single-access dual-lumen ProtekDuo cannula. Median time on OxyRVAD was 12 days (interquartile range 8-23 days), and survival to ICU discharge was 63.9%. Device-related complications were infrequently reported. CONCLUSION: OxyRVAD support is a promising alternative for RV support when gas exchange is compromised, with good ICU survival in selected cases. Comparative analyses in patients with RV failure with and without severe lung disease are needed.

Randomized trial of routine versus on-demand intraoperative extracorporeal membrane oxygenation in lung transplantation: A feasibility study.

In most centers, extracorporeal membrane oxygenation (ECMO) is the preferred means to provide cardiopulmonary support during lung transplantation. However, there is controversy about whether intraoperative venoarterial (VA) ECMO should be used routinely or selectively. A randomized controlled trial is the best way to address this controversy. In this publication, we describe a feasibility study to assess the practicality of a protocol comparing routine versus selective VA-ECMO during lung transplantation. This prospective, single-center, randomized controlled trial screened all patients undergoing lung transplantation. Exclusion criteria include retransplantation, multiorgan transplantation, and cases where ECMO is mandatory. We determined that the trial would be feasible if we could recruit 19 participants over 6 months with less than 10% protocol violations. Based on the completed feasibility study, we conclude that the protocol is feasible and safe, giving us the impetus to pursue a multicenter trial with little risk of failure due to low recruitment.

Defining Optimal Settings for Lung Cryobiopsy in End-Stage Pulmonary Disease. A Human, Ex Vivo, Diseased Lung Clinical Trial.

BACKGROUND: To evaluate optimal settings of probe size, freezing time, and distance to the pleura that influence the size and quality of biopsy specimens during transbronchial lung cryobiopsies in ESPD. METHODS: We prospectively recruited 17 patients undergoing lung transplantation. We created a nonperfused ex vivo bronchoscopy setting to perform multiple cryobiopsies with different probe sizes (1.7, 1.9, and 2.4 mm), freezing times (3, 5, 7, 10, 20, 30 seconds), and probe distance from pleura (5, 10, and 20 mm). Alveolated pulmonary parenchyma area≥50% in histology was considered a good quality biopsy, with a minimum procedural artifact. We used logistic regression to identify independent parameters as risk factors for histologic adequacy. RESULTS: A total of 545 cryobiopsies were obtained from 34 explanted lungs after pneumonectomy for lung transplantation. The mean maximum diameter of the specimen achieved with the 1.7 probe was larger (13.5 mm) than those obtained with 1.9 and 2.4 mm probes (11.3 and 10.7 mm, P= 0.07). More pleural macroscopic damage and pleural tissue in histology occurred with the 2.4 mm probe ( P <0.001). There was no difference in the quality of specimens between the different freezing times and the distance from the pleura. CONCLUSIONS: Freezing time and distance from the pleura did not affect the histologic quality for diagnosing ESPD in severely damaged lungs. Smaller cryoprobe size did not negatively affect sample adequacy.

Outside the Cage Subcostal RATS Lobectomy: Technical Aspects and Results of the First Series of a Novel Approach to Pulmonary Lobectomy.

OBJECTIVE: The goal of minimally invasive surgery is to reduce trauma to patients and improve their postoperative outcomes. In this context, the utilization of robot-assisted thoracic surgery (RATS) in the treatment of lung cancer has increased worldwide. The feasibility of single-incision major pulmonary resections by RATS was recently reported, with the objective of minimizing the surgical trauma of the traditional multiportal RATS approach. However, both techniques require intercostal incisions, potentially causing immediate and chronic pain resulting from intercostal nerve injury. To reduce postoperative pain resulting from intercostal approaches, we developed a nonintercostal, outside the thoracic cage (OTC) approach for RATS lobectomy, avoiding intercostal instrumentation. This report aims to describe the results of the first reported series of OTC subcostal RATS lobectomies. METHODS: Retrospective analysis of a series of the first consecutive patients operated on using the novel OTC subcostal RATS lobectomy technique. RESULTS: Between August and December 2022, a total of 10 consecutive cases were analyzed. The median age was 63 (55 to 84) years, the mean body mass index was 29 (24 to 45) kg/m2, and the median American Society of Anesthesiologists score was III (II to IV). No serious adverse events were observed, and there was no conversion of the surgical technique. The mean operative time was 132.6 (98 to 223) min. The median length of stay was 2 days. No pain-related complications, readmissions, or 30-day mortality were observed. CONCLUSIONS: This series demonstrates that OTC RATS lobectomy is feasible and safe. A phase I clinical trial is currently underway to prospectively assess the safety of the technique as well as its clinical relevance.

Post-transplant outcomes among cystic fibrosis patients undergoing lung transplantation colonized by Burkholderia: A single center cohort study.

BACKGROUND: Prior infection with Burkholderia cepacia complex (BCC) has been associated with poorer outcomes after lung transplantation, posing an important dilemma for cystic fibrosis (CF). Although current guidelines consider BCC infection to be a relative contraindication, some centers continue to offer lung transplantation to BCC-infected CF patients. METHODS: We conducted a retrospective cohort study which included all consecutive CF-LTR between 2000 and 2019 to compare the postoperative survival of BCC-infected CF lung transplant recipients (CF-LTR) to BCC-uninfected patients. We used a Kaplan-Meier analysis to compare survival of BCC-infected to BCC-uninfected CF-LTR and fitted a multivariable Cox model, adjusted for age, sex, BMI and year of transplantation as potential confounders. As an exploratory analysis, Kaplan-Meier curves were also stratified by the presence of BCC and urgency of transplantation. RESULTS: A total of 205 patients were included with a mean age of 30.5 years. Seventeen patients (8%) were infected with BCC prior to LT. Patients were infected with the following species: B. multivorans5, B. vietnamiensis3, combined B. multivorans and B. vietnamiensis3 and others4. None of the patients were infected with B. cenocepacia. Three patients were infected with B. gladioli. One-year survival was 91.7% (188/205) for the entire cohort, 82.4% (14/17) among BCC-infected CF-LTR, and 92.5% (173/188) among BCC uninfected CF-LTR (crude HR = 2.19; 95%CI 0.99-4.85; p = 0.05). In the multivariable model, presence of BCC was not significantly associated with worse survival (adjusted HR 1.89; 95%CI 0.85-4.24; p = 0.12). In the stratified analysis for both presence of BCC and urgency of transplantation, urgency of transplantation among BCC-infected CF-LTR appeared to be associated with poorer outcome (p = 0.003 across the 4 subgroups). CONCLUSION: Our results suggest that non-cenocepacia BCC-infected CF-LTR have comparable survival rate to BCC-uninfected CF-LTR.

Post-Operative Outcomes Associated With Open Versus Robotic Thymectomy: A Propensity Matched Analysis.

To compare post-operative outcomes associated with thymectomy performed using either open or robotic approaches. Retrospective cohort study from a single-center prospective registry consisting of patients undergoing thymectomy between 2000 and 2020. Patients were grouped according to surgical approach (open vs robotic). A propensity-score matching analysis was performed in a 2:1 open to robotic ratio, and surgical outcomes were evaluated. We analyzed 234 thymectomies (155 open; 79 robotic). Myasthenia gravis was present in 23.2% and 32.9% (P = 0.249) in the open and in the robotic group, respectively. All covariates were balanced in the matched groups (open n = 114; robotic n =5 9), except lesion size. The robotic approach was significantly associated with shorter surgical time (median 95 vs 65 minutes, P < 0.001), lesser clinical (21.1% vs 6.8%, P = 0.016) and surgical (11.4% vs 1.7%, P = 0.036) complications during the same hospitalization, less Clavien-Dindo grade 2 or higher complication rates (28.1 vs 15.3%, P = 0.048), chest tube duration (median: 3 vs 0 days, P < 0.001) and in-hospital length of stay (median: 5 vs 0 days, P < 0.001). Bleeding (P = 0.214), ICU length of stay (P = 0.167), reoperation rate (open, 1.8% vs robotic 0%), 90-day mortality (P = 0.341) and readmission rate post discharge (P = 0.277) were similar between the groups. In the matched population with primary thymic epithelial tumors, the completeness of resection rate was similar (open, 92.1% vs robotic 96.8%, P = 0.66.). Robotic thymectomy is associated with improved post-operative outcomes when compared to open thymectomy, without compromising the goals of oncologic surgery. Longer follow-up is needed to ensure oncologic equivalence.

Surgical Cost Awareness Program Study: Impact of a Novel, Real-Time, Cost Awareness Intervention on Operating Room Expenses in Thoracoscopic Lobectomy.

BACKGROUND: For surgical patients, operating room expenses are significant drivers of overall hospitalization costs. Surgical teams often lack awareness of the costs associated with disposable surgical supplies, which may lead to unnecessary expenditures. The aim of this study is to evaluate whether a Surgical Cost Awareness Program would reduce operating room costs. STUDY DESIGN: A prototype software displays the types and costs of disposable instruments used in real-time during surgery and generates insight-driven operative cost reports, which are automatically sent to the surgeons. A prospective pre-post controlled trial of thoracoscopic lobectomy procedures performed by 7 surgeons at a single academic center was conducted. Control and intervention groups consisted of consecutive cases from February 2nd through June 23, 2021, and from June 28th through December 22, 2021, respectively. The primary outcome was mean per case surgical disposables cost. RESULTS: Three hundred twenty-two lobectomies were evaluated throughout the study period (control: n = 164; intervention: n = 158). Baseline characteristics were comparable between groups. Mean disposables cost per case was $3,320.73 ± $814.83 in the control group compared with $2,567.64 ± $594.59 in the intervention group, representing a mean cost reduction of $753.08 (95% CI, $622.29 to $883.87; p < 0.001). All surgeons experienced a reduction in disposable costs after the intervention. Intraoperative and postoperative outcomes did not differ between the cohorts. CONCLUSIONS: Providing real-time educational feedback to surgical teams significantly reduced costs associated with disposable surgical equipment without compromising perioperative outcomes for lobectomy. Integrating the novel AssistIQ software across other procedural settings may generate further data insights with the potential for significant cost savings on a larger scale.

Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation.

Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammatory process through neutrophil extracellular traps (NETs) release (NETosis). NETs are composed of DNA filaments decorated with granular proteins contributing to vascular occlusion associated with PGD. The main objective was to correlate NETosis in PGD3 (n = 9) versus non-PGD3 (n = 27) recipients in an exploratory study. Clinical data and blood samples were collected from donors and recipients pre-, intra- and postoperatively (up to 72 h). Inflammatory inducers of NETs' release (IL-8, IL-6 and C-reactive protein [CRP]) and components (myeloperoxidase [MPO], MPO-DNA complexes and cell-free DNA [cfDNA]) were quantified by ELISA. When available, histology, immunohistochemistry and immunofluorescence techniques were performed on lung biopsies from donor grafts collected during the surgery to evaluate the presence of activated neutrophils and NETs. Lung biopsies from donor grafts collected during transplantation presented various degrees of vascular occlusion including neutrophils undergoing NETosis. Additionally, in recipients intra- and postoperatively, circulating inflammatory (IL-6, IL-8) and NETosis biomarkers (MPO-DNA, MPO, cfDNA) were up to 4-fold higher in PGD3 recipients compared to non-PGD3 (p = 0.041 to 0.001). In summary, perioperative elevation of NETosis biomarkers is associated with PGD3 following human lung transplantation and these biomarkers might serve to identify recipients at risk of PGD3 and initiate preventive therapies.

New-onset Obesity After Lung Transplantation: Incidence, Risk Factors, and Clinical Outcomes.

BACKGROUND: Lung transplant (LTx) recipients who gain weight after transplantation may experience an upward shift in body mass index (BMI) that places them in the obese category. The incidence, risk factors, and impact on metabolic health and mortality of new-onset obesity have not been documented in the LTx setting. METHODS: This single-center retrospective study included 564 LTx recipients. Individuals were stratified according to their BMI trajectories from pretransplant evaluation up to 10 y posttransplant. New-onset obesity was defined as a pretransplant BMI <30 kg/m 2 and posttransplant BMI >30 kg/m 2 . The incidence, risk factors, and posttransplant diabetes mellitus, metabolic syndrome, and mortality of recipients with new-onset obesity were compared with those of nonobese (BMI <30 kg/m 2 , pre/post-LTx), consistently obese (BMI >30 kg/m 2 , pre/post-LTx), and obese recipients with weight loss (BMI >30 kg/m 2 pre-LTx, BMI <30 kg/m 2 post-LTx). RESULTS: We found that 14% of recipients developed obesity after transplantation. Overweight individuals (odds ratio [OR]: 9.01; 95% confidence interval [CI] [4.86-16.69]; P < 0.001) and candidates with chronic obstructive pulmonary disease (OR: 6.93; 95% CI [2.30-20.85]; P = 0.001) and other diagnoses (OR: 4.28; 95% CI [1.22-14.98]; P = 0.023) were at greater risk. Multivariable regression analysis showed that new-onset obesity was associated with a greater risk of metabolic syndrome (hazard ratio: 1.70; 95% CI [1.17-2.46]; P = 0.005), but not of posttransplant diabetes mellitus, than nonobesity. Recipients with new-onset obesity had a survival comparable to that of consistently obese individuals. CONCLUSIONS: A greater understanding of the multifaceted nature of post-LTx obesity may lead to interventions that are better tailored to the characteristics of these individuals.

Voriconazole therapeutic drug monitoring among lung transplant recipients receiving targeted therapy for invasive aspergillosis.

BACKGROUND: Voriconazole is the first line treatment for invasive aspergillosis (IA) Current guidelines suggest performing regular voriconazole therapeutic drug monitoring (TDM) to optimize treatment efficacy. We aimed to determine if TDM was predictive of clinical outcome in LTRs. METHODS: Retrospective chart review was performed for all LTRs with probable or proven IA, treated with voriconazole monotherapy and who underwent TDM during therapy. Clinical outcome and toxicity were measured at 12 weeks. Classification and regression tree (CART) analysis was used to determine the most predictive voriconazole level thresholds for successful outcome. RESULTS: One hundred and eighteen TDM samples from 30 LTRs with IA were analyzed. Three LTRs were excluded due to early treatment discontinuation. The median TDM level was 1.2 µg/ml (range 0.06-7.3). At 12 weeks, 62% (17/27) of patients had a successful outcome, while 37% (10/27) of patients failed therapy. CART analysis determined that the best predictor for successful outcome was a median TDM level >0.72 µg/ml. Seventy percent (14/20) of patients with median TDM above 0.72 µg/ml had a successful outcome, compared to 42.9% (3/7) of patients with a median TDM below 0.72 µg/ml (OR 3.11; 95% CI: 0.53-20.4; P = 0.21). CART analysis determined that a TDM level greater than 2.13 µg/ml was predictive of hepatotoxicity. CONCLUSIONS: Our data suggests that a voriconazole TDM range between 0.72 µg/ml and 2.13 µg/ml may be associated with improved outcomes. Our study is in line with current recommendations on the use of voriconazole TDM in improving outcome and minimizing toxicity in LTR with IA.

Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterised by exuberant tissue remodelling and associated with high unmet medical needs. Outcomes are even worse when IPF results in secondary pulmonary hypertension (PH). Importantly, exaggerated resistance to cell death, excessive proliferation and enhanced synthetic capacity are key endophenotypes of both fibroblasts and pulmonary artery smooth muscle cells, suggesting shared molecular pathways. Under persistent injury, sustained activation of the DNA damage response (DDR) is integral to the preservation of cells survival and their capacity to proliferate. Checkpoint kinases 1 and 2 (CHK1/2) are key components of the DDR. The objective of this study was to assess the role of CHK1/2 in the development and progression of IPF and IPF+PH. METHODS AND RESULTS: Increased expression of DNA damage markers and CHK1/2 were observed in lungs, remodelled pulmonary arteries and isolated fibroblasts from IPF patients and animal models. Blockade of CHK1/2 expression or activity-induced DNA damage overload and reverted the apoptosis-resistant and fibroproliferative phenotype of disease cells. Moreover, inhibition of CHK1/2 was sufficient to interfere with transforming growth factor beta 1-mediated fibroblast activation. Importantly, pharmacological inhibition of CHK1/2 using LY2606368 attenuated fibrosis and pulmonary vascular remodelling leading to improvement in respiratory mechanics and haemodynamic parameters in two animal models mimicking IPF and IPF+PH. CONCLUSION: This study identifies CHK1/2 as key regulators of lung fibrosis and provides a proof of principle for CHK1/2 inhibition as a potential novel therapeutic option for IPF and IPF+PH.

Impact of Volume on Mortality and Hospital Stay After Lung Cancer Surgery in a Single-Payer System.

BACKGROUND: There is a literature gap for hospitals in single-payer health care systems quantifying the influence of hospital volume on outcomes after major lung cancer resection. We aimed to determine the effect of hospital volume on mortality and length of stay. METHODS: A retrospective cohort study using administrative, population-based data from a single-payer universal health care system was performed in adults with non-small cell lung cancer who underwent lobectomy or pneumonectomy between 2008 and 2017. Hospital volume was defined as the average annual number of major lung resections performed at each institution. Length of stay and postoperative mortality were compared using multivariable linear and nonlinear regression between hospital volume categories and continuously. Adjusted association between hospital volume and postoperative mortality was determined by multivariable logistic regression. RESULTS: In all, 10 831 lung resections were performed: 1237 pneumonectomies and 9594 lobectomies. Patients undergoing lobectomy at high-volume hospitals had shorter median length of stay (6 vs 8 days, P = .001) compared with low-volume hospitals. After adjusting for confounders, surgery at a high-volume center was significantly associated with shorter length of stay after lobectomy and overall resections (P ≤ .001), but not after pneumonectomy (P = .787). Surgery at a high-volume center was positively associated with improved 90-day mortality in lobectomy and overall procedures (odds ratio 0.607 [95% confidence interval, 0.399 to 0.925], and 0.632 [95% confidence interval, 0.441 to 0.904], respectively). Volume was not a predictor of 90-day mortality after pneumonectomy (odds ratio 0.533 [95% confidence interval, 0.257 to 1.104], P = .090). CONCLUSIONS: Surgery at a high-volume center was positively correlated with improved 90-day survival and shorter hospital length of stay. The results support regionalized lung cancer care in a single-payer health care system.

Lung Cryobiopsy Outside of the Operating Room: A Safe Alternative to Surgical Biopsy.

OBJECTIVE: Transbronchial lung cryobiopsy (TBLC) is a promising technique that can provide a histologic diagnosis in interstitial lung diseases (ILD) and is an alternative to surgical lung biopsy. The main concerns with the procedure are safety and diagnostic accuracy. The technique is applicable in patients unable to undergo surgical biopsy due to severe comorbidities or when patient transport to the operating room is dangerous. This study reports the initial experience with TBLC on a thoracic surgical service as a first attempt at diagnosis in patients with diffuse parenchymal lung diseases (DPLD). METHODS: Between May 2018 and July 2020, 32 patients underwent TBLC using bedside flexible bronchoscopy for suspected ILD on a thoracic surgical endoscopy service. Retrospective evaluation of the procedure details, complications, and diagnostic yield were analyzed and reported. RESULTS: A total of 89 pathological samples were obtained (mean 2.8 per patient). Pneumothorax and minor bleeding occurred in 25% and 16.7% of patients, respectively. Sixty-seven percent of complications occurred with use of the 2.4 mm cryoprobe (P = 0.036). Concordance between the histologic diagnosis and final clinical diagnosis was observed in 62.5% of patients and the pathology guided the final treatment in 71% (P = 0.027) with Kappa-concordance of 0.60 (P < 0.001). CONCLUSIONS: Cryobiopsy is becoming part of the diagnostic evaluation in patients with indeterminate DPLD or hypoxemic respiratory failure. TBLC is easy to perform and has a favorable safety profile. Thoracic specialists should consider adding TBLC to their procedural armamentarium as a first option for patients with indeterminate PLD.

Long-term bone mineral density changes and fractures in lung transplant recipients with cystic fibrosis.

BACKGROUND: Little is known about long-term bone mineral density (BMD) changes and fractures in lung transplant recipients with cystic fibrosis (CF). We examined femur and lumbar spine (LS) BMD changes in men and women with CF up to 10 years post-transplant and documented post-transplant fracture prevalence. METHODS: Retrospective study of individuals who had undergone a lung transplant (2000-2015) and had a pre-transplant and at least one BMD measurement after transplant. Vertebral fractures were assessed on chest computed tomography scans and other fractures abstracted from medical records. RESULTS: The cohort consisted of 131 individuals; 53% males, median age: 28 years [interquartile range: 24-35] and 31% having pre-transplant low bone mass. Most recipients were given bisphosphonates after transplant with proportion reaching 94% at 10 years. Up to 10 years post-transplant, men experienced positive or little change in LS BMD, indicating minimal loss from pre-transplant values. In contrast, women displayed negative changes in BMD up to 5 years post-transplant before recovering pre-transplant BMD values by 10 years. Similar patterns were observed at the femur BMD where men demonstrated a lower bone loss and faster recovery towards pre-transplant values than women. After transplant, 88% of recipients maintained their pre-transplant bone status, 3% experienced an improvement, mostly progressing from low bone mass to normal status whereas 9% had a deterioration of their pre-transplant bone status. Twenty-seven recipients suffered fractures in the post-transplant period. CONCLUSIONS: These findings underline that lung recipients with CF remain at risk of skeletal fragility despite prompt initiation of post-transplant anti-osteoporosis therapy.

Balloon Dilation for Endosonographic Staging in Esophageal Cancer: A Phase 1 Clinical Trial.

BACKGROUND: Dilation in patients with malignant esophageal strictures precluding the passage of the endoscopic ultrasonography (EUS) scope allows complete evaluation; however, it may be associated with complications. This study evaluates the safety and clinical value of balloon dilation to complete EUS in patients with stenotic esophageal cancers. METHODS: This study consists of a phase I clinical trial. One-hundred-and fifty patients were recruited. Endoscopic balloon dilation was performed before EUS in patients with high-grade stenosis. The analysis was focused on the ability to complete an endosonographic examination after dilation, 30-day morbidity, and change in the final stage or definitive management based on the completed endosonographic examination. RESULTS: Dilation was required in 55 patients (36.7%), with a complication rate of 10.9% (n = 6). Dilation allowed completion of EUS in 53 patients (96.4%), leading to a modification of the clinical stage for 18 patients (34%) and a deviation in the treatment plan in 7 patients (13.2%). No differences were found in these variables when compared with the group that did not require dilation (26.3% and 14.7%, P = .33 and P = .79, respectively). Dilation was associated with more advanced disease on final pathology among patients who underwent surgical resection (P = .006). CONCLUSIONS: High-grade malignant esophageal strictures that preclude the passage of the ultrasound probe are associated with advanced stage disease. Owing to the high risk of perforation and the limited benefit in staging, balloon dilation to complete the EUS staging should be avoided. (Clinicaltrials.gov identifier: NCT01950442.).

Heat production during pulmonary artery sealing with energy vessel-sealing devices in a swine model.

OBJECTIVES: Energy vessel-sealing devices are being increasingly utilized to seal pulmonary artery (PA) branches during lobectomy. Heat from these devices can potentially injure surrounding tissues. We evaluated heat production from devices in a live animal model. METHODS: PA branches were sealed in pigs with 4 energy vessel-sealing devices: 2 ultrasonic (US), 1 advanced bipolar or 1 mixed US and bipolar (mixed) device. Thermocouples were implanted in tissue surrounding the PA branch being sealed to measure tissue temperature. A thermal camera measured the sealing site and the temperatures of the instruments. Pathological analysis was performed on PA stumps to identify thermal damage. RESULTS: A total of 37 PA branches were sealed in 4 pigs. Maximum tissue heat measured by the thermocouples for the 2 US, advanced bipolar and mixed devices was 42, 39, 42 and 46°C, respectively. The mean tissue temperatures at the site of the sealing measured with the thermal camera were 78, 75, 70 and 82°C (P = 0.834) and the mean instrument blade temperatures were 224, 195, 83 and 170°C (P = 0.000005) for the 2 US, advanced bipolar and mixed devices, respectively. The mean diameter of the region with tissue reaching 60°C or more measured with the thermal camera was between 4 and 6 mm for the 4 devices (P = 0.941). On pathological analysis, PA stumps had either thermal damage on the adventitia and external media (26/37) or transmural damage (11/37) at 1 mm from sealed site. CONCLUSIONS: A 3-mm safety margin between the instrument blades and vital structures is recommended. Instrument blades can reach high temperatures that may cause tissue damage.

HSP90 Inhibitor Improves Lung Protection in Porcine Model of Donation After Circulatory Arrest.

BACKGROUND: Ischemia-reperfusion associated with prolonged warm ischemia during donation after circulatory death (DCD) induces acute lung injury. The objective of this study was to combine ex vivo lung perfusion (EVLP) and a heat shock protein-90 inhibitor (HSP90i) to recondition DCD organs and prevent primary graft dysfunction. METHODS: Pigs (55 to 65 kg) were anesthetized, ventilated, and hemodynamically monitored. Cardiac arrest was induced with potassium chloride, and animals were left nonventilated for 2 hours. Lungs were procured and perfused in an EVLP platform for 4 hours by using a cellular perfusate. In the study group, the perfusate contained HSP90i and its transport vehicle (n = 4). In the control group, the perfusate contained only the transport vehicle (n = 4). Gas exchange, airway pressures, and compliance were measured. Pulmonary edema was assessed by bronchoscopy and weight measurement. Lung biopsy samples were obtained for histologic analyses and protein expression measurements. RESULTS: The use of HSP90i reduced lung weight gain to 8.4 ± 3.4% vs 26.6 ± 6.2% in the control group (P < .05). There was reduced edema formation. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at the end of EVLP was 423 ± 65 in the study group vs 339 ± 25 mm Hg in the control group, but this difference was not statistically significant. Lactate metabolism, pulmonary vascular resistance, and pulmonary arterial pressure improved during EVLP with the use of the HSP90i. CONCLUSIONS: The use of HSP90i with EVLP improves the lung reconditioning process. Further research is required to confirm whether these findings translate to benefit once transplanted and observed in vivo. Successful pharmacologic inhibitors may expand the donor pool in the context of DCD donors.

Enhanced recovery after video-assisted thoracoscopic surgery lobectomy: a prospective, historically controlled, propensity-matched clinical study.

Background: Enhanced recovery pathways or fast-tracking following surgery can decrease the rate of postoperative complications and hospital length of stay. The objectives of this study were to implement an enhanced recovery after surgery (ERAS) pathway for patients undergoing a video-assisted thoracoscopic surgery (VATS) lobectomy, to assess the safety and efficiency of this protocol by measuring associated postoperative outcomes, and to compare the outcomes for patients in the ERAS group with the outcomes for patients in a propensity-matched control group. Methods: The study was a prospective clinical trial. Patients who were scheduled to undergo VATS lobectomy at the Centre hospitalier de l'Université de Montréal in Montréal, Quebec, Canada, were enrolled between November 2015 and October 2016. The ERAS pathway was used for all enrolled patients. The primary outcome was the number and severity of complications measured by the Comprehensive Complication Index. Secondary outcomes included length of stay, readmission and recovery. Recovery of patients was measured using EQ-5D-5L preoperatively and at 1 week, 1 month and 4 months after surgery. Prospectively enrolled patients were propensity matched to historical controls. Results: Ninety-eight patients (36 men and 62 women) in the ERAS group and 98 patients in the control group (29 men and 69 women) were included in the analysis. The mean age was 65.2 ± 9.3 years, the mean body mass index (BMI) was 26.9 ± 5.9 kg/m2 and the median Charlson Comorbidity Index score was 2 (interquartile range [IQR] 2-3) in the ERAS group. In the control group, the mean age was 66.2 ± 9.4 years, the mean BMI was 27.4 ± 5.6 kg/m2 and the median Charlson Comorbidity Index score was 3 (IQR 2-3). A total of 23 patients (23.4%) in the ERAS group and 28 (28.6%) in the control group experienced 1 or more postoperative complications. The mean Comprehensive Complication Index score was 7.4 ± 16.8 in the ERAS group compared with 8.0 ± 14.3 in the control group (p = 0.79). The median postoperative length of stay was 3 days in the ERAS group and 5 days in the control group (p < 0.001). Five patients in the ERAS group and 4 patients in the control group were readmitted. The protocol adherence rate was 64.3%. Conclusion: It is feasible to implement an enhanced recovery protocol after VATS lobectomy. Although the pathway is still early in its development in Canada, implementation of an ERAS pathway after VATS lobectomy was associated with decreased length of stay, with no observable increase in complication or readmission rates.

Contexte: Les protocoles de récupération optimisée, ou réhabilitation précoce, après une intervention chirurgicale permettent de réduire les taux de complications postopératoires et d'abréger le séjour hospitalier. Les objectifs de cette étude étaient d'appliquer les principes de récupération optimisée après une chirurgie (ou ERAS, enhanced recovery after surgery) à des patients soumis à une lobectomie par chirurgie thoracique vidéo-assistée (CTVA), d'évaluer l'innocuité et l'efficience d'un tel protocole en mesurant les paramètres postopératoires associés, et de comparer l'issue de l'intervention chez les patients du groupe ERAS à celle des patients d'un groupe témoin apparié par score de propension. Méthodes: Il s'agit d'un essai clinique prospectif. Des patients qui devaient subir une lobectomie par CTVA au Centre hospitalier de l'Université de Montréal, à Montréal, Québec, Canada, ont été recrutés entre novembre 2015 et octobre 2016. Les principes ERAS ont été appliqués à tous les patients inscrits. Le paramètre principal était le nombre et la gravité des complications mesurés à l'aide de l'Indice global de complications. Les paramètres secondaires incluaient la durée du séjour, les réadmissions et le rétablissement. Le rétablissement des patients a été mesuré à l'aide du questionnaire EQ-5D-5L avant, puis 1 semaine, 1 mois et 4 mois après la chirurgie. Les patients recrutés prospectivement ont été assortis à des témoins historiques par score de propension. Résultats: Au total, 98 patients (36 hommes et 62 femmes) du groupe ERAS et 98 patients du groupe témoin (29 hommes et 69 femmes) ont été inclus dans l'analyse. L'âge moyen était de 65,2 ± 9,3 ans, l'indice de masse corporelle (IMC) moyen était de 26,9 ± 5,9 kg/m2 et l'indice de comorbidité de Charlson médian était de 2 (éventail interquartile [ÉIQ] 2­3) dans le groupe ERAS. Dans le groupe témoin, l'âge moyen était de 66,2 ± 9,4 ans, l'IMC moyen était de 27,4 ± 5,6 kg/m2 et l'indice de comorbidité de Charlson médian était de 3 (ÉIQ 2­3). En tout, 23 patients (23,4 %) du groupe ERAS et 28 (28,6 %) du groupe témoin ont présenté au moins une complication postopératoire. L'Indice global de complications a été de 7,4 ± 16,8 dans le groupe ERAS, contre 8,0 ± 14,3 dans le groupe témoin (p = 0,79). La durée médiane du séjour postopératoire a été de 3 jours dans le groupe ERAS et de 5 jours dans le groupe témoin (p < 0,001). Cinq patients du groupe ERAS et 4 patients du groupe témoin ont été réadmis. Le taux d'adhésion au protocole a été de 64,3 %. Conclusion: Il est possible d'appliquer un protocole de récupération optimisée après la lobectomie par CTVA. Même si ce protocole en est encore à ses débuts au Canada, l'application de principes ERAS après la lobectomie par CTVA a été associée à un abrègement du séjour hospitalier, sans augmentation observable des taux de complications ou de réadmissions.

Combined Endosonographic Mediastinal Lymph Node Staging in Positron Emission Tomography and Computed Tomography Node-Negative Non-Small-Cell Lung Cancer in High-Risk Patients.

Positron emission tomography (PET) with computed tomography (CT) is routinely utilized to investigate lymph node (LN) metastases in non-small-cell lung cancer. However, it is less sensitive in normal-sized LNs. This study was performed in order to define the prevalence of mediastinal LN metastases discovered on combined endosonography by endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) fine needle aspiration in patients with a radiologically normal mediastinum. This study consists of a retrospective, single-institution, tertiary care referral center review of a prospectively maintained database. Patients were identified from a cohort between January 2009 and December 2014. One hundred and sixty-one patients with biopsy-proven, non-small-cell lung cancer were identified in whom both the preendosonography CT and PET-CT were negative for mediastinal LN metastases. Combined endosonography (EBUS + EUS-FNA) was performed in all patients. Z test was used for statistical analysis. A P value of <0.05 was considered statistically significant. A total of 161 consecutive patients were included. Patients were staged if they had central tumor, tumor size >3 cm, N1 lymph node involvement on PET-CT/CT, or if there was low SUV (<2.5) in the primary tumor. A total of 416 lymph nodes were biopsied in the 161 patients using combined endosonography; 147 with EBUS and 269 with EUS. Mean and median number of lymph nodes biopsied per patient using combined EBUS/EUS was 2.5 and 3, respectively (mean and median EBUS: 0.91 and 2.5; mean and median EUS 1.6 and 3). Endosonographic staging upstaged 13% of patients with radiologically normal lymph nodes in the mediastinum, hilum, lobar, and sublobar regions (confidence interval 8.22-19.20). Twenty-one out of 161 patients (13%) with radiologically normal mediastinum were positive on combined EBUS/EUS staging. Out of 21 patients upstaged on endosonography, 15 (71%) had tumor size >3 cm. Six (28%) had occult N1 disease. Thirteen (61%) had occult N2 disease and 2 (9%) had adrenal involvement. None of the upstaged patients had N1 LN involvement on PET-CT or CT scan. Combined endosonographic lymph node staging should be considered in the pretreatment staging of high-risk patients with non-small-cell lung cancer in the presence of radiologically normal mediastinal lymph nodes due to the significant rate of radiologically occult lymph node metastases.