Impact of Transplant Body Mass Index and Post-Transplant Weight Changes on the Development of Chronic Lung Allograft Dysfunction Phenotypes.

INTRODUCTION: Chronic lung allograft dysfunction (CLAD) is a lung transplant complication for which four phenotypes are recognized: Bronchiolitis obliterans syndrome (BOS), Restrictive allograft syndrome (RAS), mixed and undefined phenotypes. Weight gain is common after transplant and may negatively impact lung function. Study objectives were to describe post-transplant weight trajectories of patients who developed (or did not) CLAD phenotypes and examine the associations between BMI at transplant, post-transplant changes in weight and BMI, and the risk of developing these phenotypes. METHODS: Adults who underwent a bilateral lung transplant between 2000 and 2020 at our institution were categorized as having (or not) one of the four CLAD phenotypes based on the proposed classification system. Demographic, anthropometric, and clinical data were retrospectively collected from medical records and analyzed. RESULTS: Study population included 579 recipients (412 [71.1%] CLAD-free, 81 [14.0%] BOS, 20 [3.5%] RAS, 59 [10.2%] mixed, and 7 [1.2%] undefined phenotype). Weight gains of greater amplitude were seen in recipients with restrictive phenotypes than CLAD-free and BOS patients within the first five years post-transplant. While the BMI category at transplant was not statistically associated with the risk of developing CLAD phenotypes, an increase in weight (Hazard ratio [HR]: 1.04, 95% CI [1.01-1.08]; P = .008) and BMI (HR: 1.13, 95% CI [1.03-1.23]; P = .008) over the post-transplant period was associated with a greater risk of RAS. CONCLUSION: Post-LTx gain in weight and BMI modestly increased the risk of RAS, adding to the list of unfavorable outcomes associated with weight gain following transplant.

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.

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.

Lung Transplant from ECMO: Current Results and Predictors of Post-transplant Mortality.

PURPOSE OF REVIEW: We examined data from the last 5 years describing extracorporeal life support (ECLS) as a bridge to lung transplantation. We assessed predictors of survival to transplantation and post-transplant mortality. RECENT FINDINGS: The number of lung transplants performed worldwide is increasing. This is accompanied by an increase in the type of patients being transplanted, including sicker patients with more advanced disease. Consequently, there is an increase in the need for bridging strategies, with varying success. Several predictors of failure have been identified. Major risk factors include retransplantation, other organ dysfunction, and deconditioning. SUMMARY: ECLS is a risky strategy but necessary for patients who would otherwise die if not bridged to transplantation. The presence of predictors for failure is not a contraindication for bridging. However, major risk factors should be approached cautiously. Other, more minor risk factors may be considered acceptable. More importantly, the strategy should be individualized for each patient to achieve the best possible outcomes.

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.

Development and Pilot Testing of an Assessment Tool for Performance of Anatomic Lung Resection.

BACKGROUND: To meet the need for competency assessment in thoracic surgery education, we developed and tested an instrument to assess trainees' ability to perform anatomic lung resection for cancer. METHODS: The Thoracic Competency Assessment Tool-Anatomic Resection for Lung Cancer (TCAT-ARC) was developed through a multistep process involving logical analysis, expert review, and simulation-based and clinical pilot testing. Validity evidence was gathered during a 6-month clinical study of trainees performing anatomic lung resections and assessments of practicing surgeons. Feedback was gathered via post-encounter questionnaires. RESULTS: A 35-item instrument was developed and was tested in the clinical validation study. Seven trainees in 4 North American institutions participated and completed 64 anatomic lung resections. Reliability was high (α = 0.93). Interobserver reliability (k = 0.73) and correlation with an existing global competency scale (k = 0.68) were moderately high. Item analysis revealed the most difficult and discriminatory items, which matched well with a conceptual understanding of lung resection. Both trainees and assessors viewed the instrument as highly educationally effective and user-friendly. Practicing surgeons outperformed trainees. CONCLUSIONS: The TCAT-ARC demonstrated early evidence of validity and reliability in assessing performance of anatomic lung resection. The instrument may be most useful early in training and as a means for providing fine-grained formative feedback about which steps have been mastered and which still require improvement. The TCAT-ARC may be used in training programs to aid in the development of trainees' competency and as a part of an aggregate assessment of trainees' overall mastery of the procedure and readiness for independent practice.

Single lung transplantation in patients with severe secondary pulmonary hypertension.

BACKGROUND: The optimal transplant strategy for patients with end-stage lung disease complicated by secondary pulmonary hypertension (PH) is controversial. The aim of this study is to define the role of single lung transplantation in this population. METHODS: We performed a retrospective study of lung transplant recipients using the Organ Procurement and Transplantation Network/United Network for Organ Sharing Standard Transplant Analysis and Research registry. Adult recipients that underwent isolated lung transplantation between May 2005 and June 2015 for end-stage lung disease because of obstructive or restrictive etiologies were identified. Patients were stratified by mean pulmonary artery pressure ([mPAP] ≥ or < 40 mm Hg) and by treatment-single (SOLT) or bilateral (BOLT) orthotopic lung transplantation. The primary outcome measure was overall survival (OS), which was estimated using the Kaplan-Meier method and compared by the log-rank test. To adjust for donor and recipient confounders, Cox proportional hazards models were developed to estimate the adjusted hazard ratio of mortality associated with elevated mPAP in SOLT and BOLT recipients. RESULTS: A total of 12,392 recipients met inclusion criteria. Of recipients undergoing SOLT, those with mPAP ≥40 were shown to have lower survival, with 5-year OS of 43.9% (95% confidence interval 36.6-52.7; p = 0.007). Of recipients undergoing BOLT, OS was superior to SOLT, and no difference in 5-year OS between mPAP ≥ and <40 was observed (p = 0.15). In the adjusted analysis, mPAP ≥40 mm Hg was found to be an independent predictor for mortality in SOLT, but not BOLT recipients. This finding remained true on multivariable analysis. In patients undergoing SOLT, mPAP ≥40 was associated with an adjusted hazard ratio for mortality of 1.31 (1.08-1.59, p = 0.07). In BOLT, mPAP was not associated with increased hazard (adjusted hazard ratio 1.04, p = 0.48). CONCLUSIONS: There is a reduced survival when a patient with severe secondary PH undergoes SOLT. This increased mortality hazard is not seen in BOLT. It appears that a BOLT may negate the adverse effect that severe PH has on OS, and may be superior to SOLT in patients with mPAP over 40 mm Hg.

Development and Pilot Testing of an Assessment Tool for Performance of Invasive Mediastinal Staging.

BACKGROUND: To develop and evaluate a surgical trainee competency assessment instrument for invasive mediastinal staging, including cervical mediastinoscopy and endobronchial ultrasound (EBUS), a comprehensive instrument was developed, the Thoracic Competency Assessment Tool-Invasive Staging (TCAT-IS), using expert review and simulated and clinical pilot-testing. METHODS: Validity and reliability evidence were collected, and item analysis was performed. Initially, a 27-item instrument was developed, which underwent expert review with members of the Canadian Association of Thoracic Surgeons (n = 86) in 2014 to 2015 (response rate, 57%). TCAT-IS was refined to 29 items in 4 competency areas: preoperative, general operative, mediastinoscopy, and EBUS. Further refinements were made based on simulated use. The final version was then used to assess competency of 5 thoracic trainees performing invasive mediastinal staging in live patients. RESULTS: Participants were assessed during 20 mediastinoscopy and 8 EBUS procedures, with 47 total assessments completed. Reliability (Cronbach's alpha = 0.94), interrater reliability (κ = 0.80), and correlation with an established global competency scale (κ = 0.75) were high. The most difficult items were "set up and adjust EBUS equipment" and "identify vascular anatomy (EBUS)." Feedback questionnaires from trainees (response rate, 80%) and surgeons (response rate, 100%) were consistently positive regarding user friendliness, utility as an assessment tool, and educational benefit. Participants believed the tool "facilitated communicating feedback to the trainee with specific areas to work on." CONCLUSIONS: TCAT-IS is an effective tool for assessing competence in invasive staging and may enhance instruction. This initial test establishes early validity and reliability evidence, supporting the use of TCAT-IS in providing structured, specific, formative assessments of competency.

Patterns of Practice in Mediastinal Lymph Node Staging for Non-Small Cell Lung Cancer in Canada.

BACKGROUND: Assessment of mediastinal lymph nodes is integral in staging patients with non-small cell lung cancer (NSCLC). This study delineated the lymph node staging practices of Canadian thoracic surgeons in patients with potentially resectable NSCLC. METHODS: A questionnaire was distributed to Canadian Association of Thoracic Surgeons members (n = 86). Items addressed the use of imaging, thresholds/methods for preoperative invasive staging, and intraoperative node staging. Comparison was made against Canadian, American, and European guidelines. RESULTS: Forty-seven surgeons (55%) responded. Although most stated they derived practices from published guidelines, a significant proportion did not reflect those recommendations. Most respondents ordered a positron emission tomography scan for every patient (87.2%), and the same proportion (87.2%) performed invasive staging selectively, with a wide range of indications. The most common thresholds were suspicious nodes on imaging (80.5%), tumor within the central third of the lung (67.5%), and tumor exceeding 3 cm (34.2%). Endobronchial ultrasound, alone or with endoscopic ultrasound, was selected as the initial staging procedure of choice by 47.9%, and 43.5% selected mediastinoscopy first. Of surgeons selecting mediastinoscopy, 61.9% reported some barriers to performing endobronchial ultrasound. There was variability, between surgeons and between lobes, in which nodes respondents harvested intraoperatively for given lobectomies. A sizeable minority (13%) did not routinely harvest lymph nodes intraoperatively. CONCLUSIONS: Determining the appropriate treatment and prognosis of NSCLC patients relies on proper staging. Significant variability exists in node staging practices in Canada as well as divergence from guidelines. This may result in understaging or overstaging patients and inappropriate care.

When Should Negative Endobronchial Ultrasonography Findings be Confirmed by a More Invasive Procedure?

The treatment of non-small cell lung cancer is largely dependent on accurate staging in order to determine appropriate therapy. Despite advances in imaging, such as computed tomography and positron emission tomography, invasive mediastinal staging is frequently needed to rule out mediastinal involvement prior to curative-intent stereotactic ablative radiotherapy or surgical resection. Surgical mediastinal staging with mediastinoscopy, or anterior mediastinotomy, were traditionally considered the gold standard for invasive mediastinal staging. Endobronchial and endoscopic ultrasound have emerged as modern techniques that are being used as first-line options instead of surgical staging. As experience is gained with these newer techniques, the need for confirmatory surgical staging continues to diminish. This article addresses the situations in which negative results should be confirmed by a more invasive procedure.

Palliation of Concomitant Tracheobronchial and Esophageal Disease Using a Combined Airway and Esophageal Approach.

BACKGROUND: Neoplastic involvement of the mediastinum can contribute to both airway and esophageal pathology. That can manifest as combined esophageal and airway stenosis, or tracheobronchoesophageal fistula. Conventional palliative treatment of these problems consists of endoluminal stent insertion. The double stenting approach consists of insertion of a tracheobronchial and an esophageal stent in parallel and allows concomitant symptomatic relief of both the airway and esophageal pathology. METHODS: The study consists of a retrospective case series of patients who underwent a double stenting procedure for concomitant airway and esophageal disease between August 2009 and September 2014. The type of airway stent chosen was determined based on the pathology and the level of the lesion (simple tubular in the mid trachea or mainstem bronchus, Y-stent for carina). RESULTS: Thirty-nine patients were treated using the double stenting approach during a combined procedure over 5 years: 15 patients with tracheobronchoesophageal fistula and 24 with stenosis. Immediate relief of symptoms, defined as resuming oral intake and breathing without an external tracheal device, was observed in 25 patients (64%). Thirty-two patients (82%) were discharged from hospital, and 7 patients died in hospital (18%). Of these 7 deaths, 6 patients died of pulmonary complications. Inhospital complications occurred in 11 patients (28%). Of the patients discharged from the hospital, 14 died during a mean follow-up period of 54 days. Mean and median survival were 49 and 24 days, respectively (range, 1 to 448), and median hospital stay was 3 days (range, 1 to 46). CONCLUSIONS: Treatment of combined airway and esophageal pathology using a double stenting approach is safe, feasible, provides reasonable immediate palliation of symptoms, and is associated with acceptable morbidity. It is a palliative procedure that allows for early hospital discharge of patients who are diagnosed with an incurable malignancy.

The efficacy of restaging endobronchial ultrasound in patients with non-small cell lung cancer after preoperative therapy.

BACKGROUND: Patient selection for surgery after neoadjuvant therapy for locally advanced non-small cell lung cancer depends on accurate restaging of mediastinal (N2) lymph nodes. Our objective is to assess the accuracy of endobronchial ultrasound (EBUS) for restaging N2 lymph nodes after neoadjuvant therapy. METHODS: This is a retrospective review of patients with non-small cell lung cancer who underwent staging with repeat computed tomography and positron emission tomography and had restaging EBUS for sampling of N2 lymph nodes. Endobronchial ultrasound was performed for suspicious nodes in stations 2R, 2L, 4R, 4L, and 7. Selected patients who were N2-negative underwent thoracotomy with complete thoracic lymphadenectomy. RESULTS: There were 32 patients with N2 disease who underwent preoperative chemotherapy or radiotherapy, or both, and subsequently had restaging EBUS. There were 3 patients who had recalcitrant N2 nodal disease detected by EBUS. There were 5 patients with pulmonary function or comorbidities that were prohibitive for surgery. Of the remaining 24 patients with negative EBUS, 3 underwent mediastinoscopy and 2 had recalcitrant N2 disease. The remaining 22 patients underwent thoracotomy. Recalcitrant N2 disease was noted in 1 patient at thoracotomy in the EBUS-assessable nodal stations. Thus EBUS was falsely negative in 3 patients. The sensitivity and negative predictive value of restaging EBUS were 50% and 88%, respectively. CONCLUSIONS: Restaging EBUS is relatively accurate at predicting the absence of metastatic disease in N2 mediastinal lymph node in patients who underwent neoadjuvant therapy for non-small cell lung cancer.

Transesophageal pulmonary nodule biopsy using endoscopic ultrasonography.

OBJECTIVE: Parenchymal pulmonary nodules located in proximity to the mediastinum, vertebral column, major vessels, or behind the heart can be technically challenging and dangerous to biopsy using traditional image-guided techniques. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) can be used to access some of these difficult to reach lesions. The purpose of the present study was to report our experience with this technique in a consecutive cohort of selected patients. METHODS: This was a retrospective cohort study. Eligible patients were identified from a prospective database. A transesophageal approach under real-time EUS guidance was performed using a 22-gauge needle. All patients underwent postprocedural chest radiography and were followed up at 30 days. RESULTS: During a 31-month period, 55 patients underwent EUS-guided lung biopsy. Confirmatory visual correlation of nodule localization within the lung parenchyma between computed tomography and EUS was possible in 100% of cases. The lung nodule distribution was 41.5% right upper lung, 18.9% right lower lung, 28.3% left upper lung, and 11.3% left lower lung. Histologic and cytologic sampling was adequate in 52 of the 55 procedures (94.5%). In all patients with adequate biopsy sampling, accurate pathocytologic diagnoses of the target parenchymal nodules were obtained. The accuracy and sensitivity of EUS-FNA were both 94.5% and consistent with the diagnosis on pathologic resection or clinical progression of disease, or both. No morbidity resulted from the procedure nor was observed at 30 days. CONCLUSIONS: EUS-FNA of parenchymal pulmonary nodules is safe and accurate and allows for biopsy of perimediastinal lung lesions not attainable using traditional techniques.

Performing robotic lobectomy and segmentectomy: cost, profitability, and outcomes.

BACKGROUND: The primary objective of this study was to evaluate our experience using a completely portal (no access incision) robotic pulmonary lobectomy or segmentectomy. METHODS: This was a retrospective review of a consecutive series of patients. RESULTS: From February 2010 until October 2013, 862 robotic operations were performed by 1 surgeon. Of these, 394 were for a planned anatomic pulmonary resection, comprising robotic lobectomy in 282, robotic segmentectomy in 71, and conversions to open in 41 (10 for bleeding, 1 patient required transfusion; and no conversions for bleeding in the last 100 patients). Indications were malignancy in 88%. A median of 17 lymph nodes were removed. Median hospital stay was 2 days. Approximate financial data yielded: median hospital charges, $32,000 per patient (total, $12.6 million); collections, 23.7%; direct costs, $13,800 per patient; and $4,750 profit per patient (total, $1.6 million). Major morbidity occurred in 9.6%. The 30-day operative mortality was 0.25%, and 90-day mortality was 0.5%. Patients reported a median pain score of 2/10 at their 3-week postoperative clinic visit. CONCLUSIONS: Robotic lobectomy for cancer offers outstanding results, with excellent lymph node removal and minimal morbidity, mortality, and pain. Despite its costs, it is profitable for the hospital system. Disadvantages include capital costs, the learning curve for the team, and the lack of lung palpation. Robotic surgery is an important tool in the armamentarium for the thoracic surgeon, but its precise role is still evolving.

Perioperative anti-tumor necrosis factor therapy does not increase the rate of early postoperative complications in Crohn's disease.

BACKGROUND: There have been numerous studies with conflicting results regarding the use of anti-tumor necrosis factor (TNF) therapy and its relationship to postoperative outcome in Crohn disease. The aim of our study was to examine the rate of postoperative morbidity in patients receiving anti TNF therapy in the perioperative period. METHODS: All patients undergoing surgery for Crohn disease from 2005 till 2008 were abstracted from a prospective database. Patients undergoing surgery which included a suture or staple line at risk for leaking were selected for the study. A retrospective review of medical records was performed. The study group comprised patients treated with perioperative anti TNF therapy (defined as treatment within 8 weeks preoperatively or up to 30 days postoperatively). The remainder of the patients did not receive perioperative anti TNF therapy. Patient characteristics, disease severity, medication use, operative intervention and 30-day complication were compared between the two groups. RESULTS: Three hundred and seventy patients were selected for analysis in this study, of which 119 received perioperative anti TNF therapy and 251 did not. The groups were similar in baseline characteristics, perioperative risk factors and procedures. The group who received perioperative anti TNF therapy had a more severe disease overall as measured by the American College of Gastroenterology (ACG) categories of disease (50% severe fulminant disease in the perioperative anti-TNF therapy group versus 18% in the group that did not receive perioperative anti-TNF therapy, p < 0.001). There was no significant association of perioperative anti TNF therapy and any postoperative complications (27.9% in anti-TNF group versus 30.1% in no anti-TNF group, p = 0.63) nor intra-abdominal infectious complications (5.0% in anti-TNF group versus 7.2% in no anti-TNF group, p = 0.44). Univariate analysis showed that the only factors associated with an increase in postoperative intra-abdominal infections were age and penetrating disease. CONCLUSIONS: The use of anti-TNF therapy in the perioperative period is safe and is not associated with an increase in overall or infectious complications in Crohn disease patients undergoing surgery.