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OBJECTIVE Surgical treatment of locally advanced non-small cell lung cancer including single or multilevel N2 remains a matter of debate. Several trials demonstrate that selected patients benefit from surgery if R0 resection is achieved. We aimed to assess resectability and outcome of patients with locally advanced clinical T3/T4 (American Joint Committee on Cancer 8th edition) tumors after induction treatment followed by surgery in a pooled analysis of 3 prospective multicenter trials. METHODS A total of 197 patients with T3/T4 non-small cell lung cancer of 368 patients with stage III non-small cell lung cancer enrolled in the Swiss Group for Clinical Cancer Research 16/96, 16/00, 16/01 trials were treated with induction chemotherapy or chemoradiation therapy followed by surgery, including extended resections. Univariable and multivariable analyses were applied for analysis of outcome parameters. RESULTS Patients' median age was 60 years, and 67% were male. A total of 38 of 197 patients were not resected for technical (81%) or medical (19%) reasons. A total of 159 resections including 36 extended resections were performed with an 80% R0 and 13.2% pathological complete response rate. The 30- and 90-day mortality were 3% and 7%, respectively, without a difference for extended resections. Morbidity was 32% with the majority (70%) of minor grading complications. The 3-, 5-, and 10-year overall survivals for extended resections were 61% (95% confidence interval, 43-75), 44% (95% confidence interval, 27-59), and 29.5% (95% confidence interval, 13-48), respectively. R0 resection was associated with improved overall survival (hazard ratio, 0.41; P

OBJECTIVES Recent trials have begun to explore immune checkpoint inhibitors for non-small cell lung cancer in the neoadjuvant setting, but data on tumour response and surgical outcome remain limited. METHODS Retrospective evaluation of clinical data from patients with non-small cell lung cancer treated with immune checkpoint inhibitors followed by lung resection was performed at 2 large volume institutions (1 North American, 1 European). Data were analysed using Chi-squared, Fisher’s and Wilcoxon rank-sum tests where appropriate. RESULTS Thirty-seven patients were identified from 2017 to 2019. Forty-nine per cent were Stage IIIB and IV. Forty-six per cent received immunotherapy alone and 54% in combination with chemo- and/or radiotherapy. Sixteen per cent of cases were successfully performed minimally invasively. Twenty patients were operated with lobectomy (6 of these with wedges or segments of a neighbouring lobe, 2 with sleeve resections and 1 with a chest wall resection), 4 with bilobectomies, 11 with pneumonectomy (including 5 extrapleural pneumonectomies and 1 atrial resection) and 1 with a wedge resection. Overall, 10 patients (27%) developed postoperative complications and the 90-day mortality was zero. One-year recurrence-free survival was 73% for stage II/IIIA and 55% for stage IIIB/stage IV. The major pathologic response rate was 34%. CONCLUSION In this retrospective study, lung resection after immunotherapy (alone or in combination) is safe, although often requires complex surgery. Due to increasing number of clinical trials adopting immunotherapy in the neoadjuvant setting, it is likely that this therapy will become part of standard of care. Immunotherapy may also allow surgery to have a role for selected patients with advanced disease.

BACKGROUND Cadaveric lobar lung transplantation (L-LTx) is developed to overcome donor-recipient size mismatch. Controversial short- and long-term outcomes following L-LTx have been reported compared to full-sized lung transplantation (F-LTx). This study reports long-term outcomes after L-LTx. METHODS We reviewed patients undergoing lung transplantation (LTx) between 2000 and 2016. The decision to perform L-LTx was made based mainly on donor-recipient height discrepancy and visual assessment of donor lungs. Predicted donor-recipient total lung capacity (TLC) ratio was calculated more recently. Primary outcome was overall survival. RESULTS In all, 370 bilateral LTx were performed during the study period, among those 250 (67%) underwent F-LTx and 120 (32%) underwent L-LTx, respectively. One- and 5-year survival rates were 85% vs. 90% and 53% vs. 63% for L-LTx and F-LTx, respectively (p = 0.16). Chronic lung allograft dysfunction (CLAD)-free survival at 5 years was 48% in L-LTx vs. 51% in F-LTx recipients (p = 0.89), respectively. Age, intraoperative extracorporeal membrane oxygenation (ECMO) use, intensive care unit (ICU) stay, and postoperative renal replacement therapy (RRT) were significant prognostic factors for survival using multivariate analysis. CONCLUSIONS Overall survival and CLAD-free survival following L-LTx were comparable to F-LTx. Given the ongoing donor organ shortage, cadaveric L-LTx remains as an important resource in LTx.

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009–2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient’s performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres., info:eu-repo/semantics/published

OBJECTIVES Patients with oligometastatic non-small-cell lung cancer (NSCLC) may benefit from therapy with curative intent. Our goal was to identify prognostic factors related to better prognosis in a multicentre analysis of patients who underwent surgery of primary tumours in combination with radical treatment of all metastatic sites. METHODS We retrospectively reviewed the records of oligometastatic patients who underwent resection of primary tumours at 4 centres (August 2001–February 2018). Oligometastasis was defined as ≤5 synchronous metastases in ≤2 organs. Radical metastatic treatment was surgery, radiotherapy or a combination. The Cox proportional hazards model was used for identification of prognostic factors on overall survival. RESULTS We treated 124 patients; 72 (58%) were men, mean age 60 ± 9.8 years, with 87 (70%) adenocarcinoma. Sixty-seven (54%) patients had positive pathologic-N stage (pN). Brain metastases were most common (n = 76; 61%) followed by adrenal (n = 13; 10%) and bone (n = 12; 10%). Systemic therapy was administered in 101 (82%) patients. Median follow-up was 60 months [95% confidence interval (CI) 41–86]. Thirty- and 90-day mortality rates were 0 and 2.4%, respectively. One-, 2-, and 5-year overall survival were 80%, 58% and 36%, respectively. Cox regression analysis showed that patients ≤60 years [hazard ratio (HR) 0.41, 95% CI 0.24, 0.69; P = 0.001] and patients with pN0 (HR 0.38, 95% CI 0.21–0.69; P = 0.002) had a significant survival benefit. The presence of bone metastases negatively affected survival (HR 2.53, 95% CI 1.05–6.09; P = 0.04). CONCLUSIONS Treatment with curative intent of selected oligometastatic NSCLC, including resection of the primary tumour, can be performed safely and with excellent 5-year survival rates, especially in younger patients with pN0 disease.

OBJECTIVES No significant data are available to assess whether complex sleeve lobectomy (complex-SL) can be considered comparable to conventional lobectomy (CL) in terms of surgical outcome. The purpose of this study was to compare surgical and oncological outcomes of complex-SL with CL in patients with lung cancer. METHODS Between 2000 and 2015, a total of 568 patients who underwent open CL (defined as resection of only 1 lobe) and 187 patients who underwent SL were analysed. The SL group was divided into 2 subgroups: standard-SL (bronchial SL, n = 106) and complex-SL (n = 81) (defined as bronchial sleeve resection together with another surgical intervention: bronchovascular SL, n = 40; vascular SL, n = 26; atypical bronchoplasty with resection of more than 1 lobe, n = 12; bronchial SL + chest wall resection, n = 3). RESULTS The complex-SL group had more patients with chronic obstructive pulmonary disease (COPD) (25.9% vs 12.5%, P = 0.001), neoadjuvant treatment (39.5% vs 12.0%, P CONCLUSIONS Complex-SL had a comparable outcome to CL, although the complex-SL group had more patients with advanced-stage NSCLC, low preoperative forced expiratory volume in 1 s and COPD.

For early stage non-small cell lung cancer (NSCLC) retrospective data of functionally compromised patients undergoing segmentectomy showed equal outcomes for perioperative complications and quality of life (QoL) compared with lobectomy patients. However no prospectively randomized data comparing patients eligible for both procedures are available.We conducted a prospective, randomized, multicenter phase III trial and investigated perioperative complications and QoL in patients with NSCLC stage IA (7th edition) undergoing segmentectomy versus lobectomy. The EORTC Questionnaire Core-30 (QLQ C-30) supplemented by thirteen-item lung cancer-specific module (LC13) was assessed before surgery, at discharge, 6 weeks, 3, 6 and 12 months post-surgery.108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled, whereby 54 were assigned to lobectomy and 54 to segmentectomy. Due to nodal disease, tumor size and surgical reasons estimated during the operation, eight patients of the segmentectomy group received a lobectomy. In hospital and 90 days mortality was 0% in both groups. Perioperative complications were observed in 6 (11.3%) patients after segmentectomy and in 8 patients (14.8%) after lobectomy (p = 0.563), while the 90-day morbidity were 17% and 25.9% (9 and 14 patients), respectively (p = 0.452). Twelve months after surgery, there was a significant deterioration to the baselines of physical (p 0.001) and cognitive functioning (p = 0.025), dyspnea (p 0.001) and fatigue (p = 0.003) in the lobectomy group. Dyspnea showed a faster recovery in the segmentectomy compared to lobectomy group with statistical significance (p = 0.016 after 12 months).In patients with early-stage NSCLC, segmentectomy is associated with a statistically not significant lower perioperative morbidity and appears to provide a superior recovery in QoL compared with lobectomy patients.

Background Primary pulmonary sarcoma (PPS) is a rare malignant lung neoplasm, and there is very little medical evidence about treatment of PPS. The aim of this study is to clarify the clinical characteristics and therapeutic outcome of patients who underwent surgical resection for PPS.Methods We retrospectively reviewed the records of patients who underwent surgical resection for PPS in our institution between 1995 and 2014. Cases who only underwent biopsy were excluded.Results A total of 24 patients (18 males, 6 females), with a median age of 60 (interquartile range: 44–67) years, were analyzed. The surgical procedures performed in these patients were pneumonectomy (n = 10), lobectomy (n = 11), and wedge resection (n = 3). Complete resection was achieved in 16 patients. The pathological stages (tumor, node, metastases lung cancer classification, 8th edition) of the patients were I (n = 4), II (n = 12), III (n = 2), and IV (n = 5), and there were four cases of lymph node metastasis. The 5-year overall survival rate of the patients was 50% (95% confidence interval [CI]: 29–72). Adverse prognostic factors for overall survival were incomplete resection (hazard ratio [HR]: 4.4, 95% CI: 2.1–42), advanced pathological stage (HR 14, 95% CI: 2.8–66), higher pathological grade (HR 4.5, 95% CI: 1.2–17), and tumor size ≥ 7 cm (HR 4.7, 95% CI: 1.1–21).Conclusions Our series of PPS revealed that incomplete resection, advanced pathological stage, higher pathological grade, and tumor size were unfavorable factors for long-term survival.

Background Severe emphysema is a debilitating condition with few treatment options. Lung volume reduction procedures in the treatment of severe emphysema have shown excellent results in selected patients but their exact role remains unclear with studies reporting a wide variation in outcomes. We therefore aimed to evaluate the effects of volume reduction. Methods We did a systematic review and meta-analysis. We searched MEDLINE on Sept 29, 2016, for trials of lung volume reduction in patients with emphysema, and we did an updated search on Embase and PubMed on June 18, 2018. We only included randomised controlled studies published in English evaluating the intervention with either sham or standard of care. Inclusion was limited to trials of techniques in which there was sustainable volume reduction. Primary outcomes were residual volume, FEV 1, St George's Respiratory Questionnaire (SGRQ), and 6-min walk distance (6MWT). Secondary outcomes were severe adverse events (including mortality), short-term mortality, and overall mortality. We extracted summary level data from the trial publications and where necessary we obtained unpublished data. A random-effects model with the I (2) statistic was used to determine heterogeneity and trial weight in each analysis. The study is registered with the PROSPERO database, number CRD42016045705. Findings We identified 4747 references in the search, and included 20 randomised controlled trials of lung volume reduction involving 2794 participants with emphysema. Following lung volume reduction from any of the interventions in pooled analyses (ie, surgery, endobronchial valve, endobronchial coil, or sclerosing agents), the mean differences compared with the control were reduction in residual volume of 0.58 L (95% CI -0.80 to -0.37), increase in FEV1 of 15.87% (95% CI 12.27 to 19.47), improvement in 6MWT of 43.28 m (31.36 to 55.21), and reduction in the SGRQ of 9.39 points (-10.92 to -7.86). The odds ratio for a severe adverse event, which included mortality, was 6.21 (95% CI 4.02 to 9.58) following intervention. Regression analysis showed improvements relative to the degree of volume reduction: FEV 1 (r(2) = 0.86; p Interpretation Despite limitations of high risk of bias and heterogeneity for some analyses, our results provide support that lung volume reduction in patients with severe emphysema on maximal medical treatment has clinically meaningful benefits. These benefits should be considered alongside potential adverse events. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

OBJECTIVE: Improvement in ex vivo lung perfusion protocols could increase the number of donors available for transplantation and protect the lungs from primary graft dysfunction. We hypothesize that perfusate adsorption during ex vivo lung perfusion reconditions the allograft to ischemia-reperfusion injury after lung transplantation. METHODS: Donor pig lungs were preserved for 24 hours at 4°C, followed by 6 hours of ex vivo lung perfusion according to the Toronto protocol. The perfusate was additionally adsorbed through a CytoSorb adsorber (CytoSorbents, Berlin, Germany) in the treatment group, whereas control lungs were perfused according to the standard protocol (n = 5, each). Ex vivo lung perfusion physiology and biochemistry were monitored. Upon completion of ex vivo lung perfusion, a left single lung transplantation was performed. Oxygenation function and lung mechanics were assessed during a 4-hour reperfusion period. The inflammatory response was determined during ex vivo lung perfusion and reperfusion. RESULTS: The cytokine concentrations in the perfusate were markedly lower with the adsorber, resulting in improved ex vivo lung perfusion physiology and biochemistry during the 6-hour perfusion period. Post-transplant dynamic lung compliance was markedly better during the 4-hour reperfusion period in the treatment group. Isolated allograft oxygenation function and dynamic compliance continued to be superior in the adsorber group at the end of reperfusion, accompanied by a markedly decreased local inflammatory response. CONCLUSIONS: Implementation of an additional cytokine adsorber has refined the standard ex vivo lung perfusion protocol. Furthermore, cytokine removal during ex vivo lung perfusion improved immediate post-transplant graft function together with a less intense inflammatory response to reperfusion in pigs. Further studies are warranted to understand the beneficial effects of perfusate adsorption during ex vivo lung perfusion in the clinical setting. ispartof: JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY vol:161 issue:2 pages:E109-E121 ispartof: location:United States status: published

Korrektur zu 10.1093/ejcts/ezab224

OBJECTIVES Resection of thymic tumours including the removal of both the tumour and the thymus gland (thymothymectomy; TT) is the procedure of choice and is recommended in most relevant articles in the literature. Nevertheless, in recent years, some authors have suggested that resection of the tumour (simple thymomectomy; ST) may suffice from an oncological standpoint in patients with early-stage thymoma who do not have myasthenia gravis (MG) (non-MG). The goal of our study was to compare the short- and long-term outcomes of ST versus TT in non-MG early-stage thymomas using the European Society of Thoracic Surgeons thymic database. METHODS A total of 498 non-MG patients with pathological stage I thymoma were included in the study. TT was performed in 466 (93.6%) of 498 patients who had surgery with curative intent; ST was done in 32 (6.4%). The completeness of resection, the rate of complications, the 30-day mortality, the overall recurrence and the freedom from recurrence were compared. We performed crude and propensity score-adjusted comparisons by surgical approach (ST vs TT). RESULTS TT showed the same rate of postoperative complications, 30-day mortality and postoperative length of stay as ST. The 5-year overall survival rate was 89% in the TT group and 55% in the ST group. The 5-year freedom from recurrence was 96% in the TT group and 79% in the ST group. CONCLUSION Patients with early-stage thymoma without MG who have a TT show significantly better freedom from recurrence than those who have an ST, without an increase in postoperative morbidity rate.

BACKGROUND Tracheal or cricotracheal resection is the standard of care for definitive treatment of tracheal stenosis. However, the incidence is low, the management is complex, and only a few centres have reported their experience. Therefore, more clinical reports on this topic are needed. METHODS We performed a retrospective analysis of all patients who underwent tracheal or cricotracheal resection for malignant or benign tracheal stenosis in our institution between 2001 and 2016. Fisher’s exact test was used for analysis of complications and recurrence. P-value

Objectives Adding bevacizumab, an anti-Vascular Endothelial Growth Factor (VEGF), to platinum-based chemotherapy/pemetrexed in 1$^{st}$ line treatment of advanced malignant pleural mesothelioma (MPM), significantly improved overall survival. However, increased high grade bleeding after operation was reported in patients with colorectal cancer who previously received bevacizumab. In the present analysis, we assessed for the first time the impact of adding bevacizumab to induction chemotherapy prior to surgery for mesothelioma patients. Methods Two hundred twenty-seven MPM patients, intended to be treated with induction chemotherapy followed by surgery at the University Hospital of Zurich between 2002 and December 2018, were included in the present analysis. After propensity score matching for gender, histology and age (1:3 ratio), data from 88 patients were analyzed. Sixty-six patients underwent induction chemotherapy (with cis-/carboplatin and pemetrexed: control group) alone and 22 patients underwent induction chemotherapy with the addition of bevacizumab (bevacizumab group) prior macroscopic complete resection (MCR). Perioperative and long-term outcome variables were analyzed. Results Patients undergoing combination treatment with bevacizumab had a significantly better response than with chemotherapy alone as assessed by modified RECIST (p=0.046). Intraoperative complications in the bevacizumab group (one patient), or in the control group (three patients) were not related to intraoperative bleeding. Postoperative transfusion of blood products occurred in a larger amount in the control group than in the bevacizumab group (p=0.047). Overall survival was not statistically different between both groups. Conclusion These initial data demonstrate that MCR can be performed safely after triple induction chemotherapy with bevacizumab without increased intra- and postoperative bleeding complications. Response rates were significantly improved by the addition of bevacizumab.

BACKGROUND: This retrospective study aims to identify clinical predictors of intraoperative blood loss during lung transplantation. While for other surgical specialties predictors of blood loss have been identified such as previous likewise located surgery, poor preoperative health status of patients, blood coagulation status, and use of extra corporeal circulation, predictors of blood loss during lung transplantation are not yet established. METHODS: A total of 326 lung transplants were performed between January 2000 and February 2014 at a tertiary hospital. The primary aim was to associate blood loss with the following potential predictors: pulmonary arterial hypertension, pre- or intraoperative extracorporeal life support (ECLS), previous thoracic surgery, previous lung transplant, and Charlson Comorbidity Index (CCI). Postoperative complications and 30-day mortality were secondary endpoints of the study. RESULTS: Median estimated blood loss during lung transplant was 1,500 mL (IQR, 1,000–2,875 mL). Pre- and intraoperative ECLS (P=0.02, P

Background: Radiotherapy is recommended as primary local therapy for inoperable patients with non-small cell lung cancer (NSCLC). We hypothesized that selected patients with advanced emphysema could be candidates for surgery and improved functional outcome might result in addition to low mortality and morbidity and successful cancer control when sublobar resection in a lung volume reduction surgery (LVRS) concept is applied. Methods: All patients with NSCLC and severe emphysema who underwent cancer resection in a LVRS concept between 2003 and 2015 were included for analysis. Postoperative 90-day mortality, complications, survival and lung function with forced expiratory volume in one second pre-operatively and three months postoperatively served as endpoints. Results: Fourteen patients were included. Three procedures were bilateral and eleven unilateral, eight have been performed with thoracoscopy and six with conversion to an open procedure due to adhesions. In ten patients, tumor resection was atypical and in four patients an anatomic segmentectomy was performed. All patients had lung volume reduction. Prolonged air leak occurred in three patients. Perioperative 90-mortality was zero. Median pre-operative forced expiratory volume in one second was 32.5% and increased to 37% (P=0.002) 3 months following surgery. Three and 5-year survival rates were 50% and 35%, respectively. Conclusions: Sublobar resection of NSCLC combined with LVRS in patients with severely impaired lung function due to emphysema can be performed with low mortality and morbidity making it an alternative treatment modality to radiotherapy. This approach allows cancer resection in marginal patients and improves emphysema symptoms simultaneously.

OBJECTIVES Abdominal surgery after lung transplantation is an important factor for major morbidity and mortality. Herein, we describe the incidence and outcome of abdominal surgery occurring early or late after transplantation. METHODS Overall, 315 patients who underwent lung transplantation between January 2000 and December 2013 at our institution were included in a prospective database. Perioperative parameters were assessed, and complications were graded according to the Clavien-Dindo Classification. RESULTS Among 315 patients after lung transplantation, 52 patients underwent abdominal surgery, 16 during the early postoperative phase and 42 at later time points. Bowel ischaemia and perforation of the right colon were the most common reason for early surgery, with a median interval of 7 days after lung transplantation. The median survival time for patients with early abdominal surgery was 31 months compared to 40 and 90 months for patients with no or late abdominal surgery (P = 0.001 and P = 0.002, respectively). The most common late indications for surgery were perforated diverticulitis, ileus and hernia, with a median interval of 37.9 months after lung transplantation and a median survival comparable with patients without any abdominal surgery (P = 0.9). However, prior hospitalization due to a non-abdominal disease was associated with increased morbidity (P = 0.006) after late surgery. CONCLUSIONS Early abdominal surgeries after lung transplantation are associated with a significant mortality risk. Abdominal operations at late time points have a favourable outcome unless patients were hospitalized prior to the abdominal complication. Clinical trial registration number ZH-KEK-Nr. 2014-0244.

Background Lung volume reduction surgery (LVRS) has been proven to be a successful procedure and can be performed with low mortality when defined selection criteria are met. We hypothesized good outcome and low mortality after LVRS for selected patients with severe hyperinflation and nonhomogeneous morphology even when diffusion capacity of the lung for carbon monoxide (Dlco) is less than 20%. Methods The study included all patients scheduled for LVRS between March 2005 and May 2014 with a preoperative Dlco of less than 20%. Postoperative 90-day mortality was the primary end point. Secondary end points were postoperative lung function and surgical morbidity at 3, 6, and 12 months. Results Included were 33 patients with a median forced expiratory volume in 1 second of 23% (interquartile range, 19% to 28%), a median diffusion capacity of 15% (interquartile range, 13% to 18%), and a median hyperinflation of 76% (residual volume–to–total lung capacity ratio of 70% to 76%). Mean follow-up was 44.8 months (range, 10 to 141 months). Heterogeneous emphysema was present in 26 patients, and 7 showed intermediately heterogeneous morphology. Sixteen procedures were bilateral, and 31 were performed by video-assisted thoracoscopic surgery. The 90-day mortality was 0%. Median forced expiratory volume in 1 second percentage predicted at 3 months increased from 23% to 29% ( p p p p = 0.028). Conclusions Selected patients with severely impaired Dlco of less than 20% can cautiously be considered as potential candidates if hyperinflation is severe and the lungs show areas with advanced destruction as targets for resection.

As large registries show an increased risk for lung transplant recipients aged 60 years or more, few single centers report favorable outcomes for carefully selected older recipients without providing essential details. The purpose of our study was to determine variables that influence survival in the elderly.All adult bilateral first lung transplants between January 2000 and December 2014 were divided in 2 groups: those aged less than 60 years (N = 223) and those aged 60 years or more (N = 83). The Charlson-Deyo Index determined recipient comorbidities. The Oto Donor Score assessed donor lung quality.Recipients aged 60 years or more had a significant lower median survival compared with their younger counterparts (48 vs 112 months, respectively, P .001). Recipient age was as an exponentially increasing univariate risk factor for mortality. By adjusting for variables in multivariate analysis, this trend was nonsignificant. The displacing variables were idiopathic pulmonary fibrosis (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.0-2.2), Charlson-Deyo Index 2 or greater (HR, 1.3; 95% CI, 1.0-1.8), systemic hypertension (HR, 1.7; 95% CI, 1.2-2.6), gastroesophageal reflux (HR, 1.9; 95% CI, 1.1-3.1), diverticulosis (HR, 1.7; 95% CI, 1.0-2.7), and an Oto Donor Score 8 or greater (HR, 1.5; 95% CI, 1.1-2.0). All of these risk factors were significantly more likely to occur in recipients aged 60 years or more, except for a tendency for high Charlson-Deyo Index.The comorbidity profile, underlying disease, and donor lung quality appear to be more important than age in reducing long-term survival. Older age serves as a marker for a complex constellation of factors that might be considered the relative or absolute contraindication to lung transplantation rather than age, per se.

BACKGROUND: Although sevoflurane (Sevo) had been shown to ameliorate posttransplant injury in various organs, data available are inconsistent, particularly in the context of lung transplantation (Tx). We here investigated if preconditioning by Sevo can protect from posttransplant injury regarding both, primary graft dysfunction (PGD) and acute rejection (AR) after experimental lung Tx, thereby focusing on two important clinical outcome parameters. MATERIALS AND METHODS: Three experimental approaches were used: (1) BALB/c mice were preconditioned for 2 h with Sevo or a fentanyl cocktail (Control; n = 10); (2) syngeneic (Syn) mouse lung Tx (C57BL/6) with a Sevo-preconditioned graft followed by 18 h storage to mimic PGD (Syn-Tx, n = 12) versus controls (fentanyl cocktail); and (3) allogeneic (Allo) Tx (BALB/c, donor; C57BL/6, recipient) to mimic AR (Allo-Tx, n = 12) versus controls (fentanyl cocktail). Syn-Tx grafts were harvested on Day 1, Allo-Tx grafts on Day 3 and analyzed for histology, immunohistochemistry, blood gas analysis, and inflammatory cytokines (enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction). RESULTS: Evaluating the preconditioning effect of Sevo only showed significantly better oxygenation (P = 0.03) and a tendency toward lower levels of lung tissue messenger RNA for tumor necrosis factor-α. In Syn-Tx recipients, the Sevo group had histologically a tendency toward an attenuation of PGD and showed significantly lower levels of interleukin 6 (P = 0.01) in plasma, but higher levels of interleukin 10 (P < 0.01) in lungs. Allo-Tx grafts in Sevo Tx recipients showed attenuated AR with histologically significantly lower rejection scores (P = 0.03), fewer classical macrophages (F4/80+; P < 0.01), but more anti-inflammatory activated macrophages (M2, CD206+; P < 0.01). Functionally, the Sevo group had a tendency toward improved oxygenation. CONCLUSIONS: We demonstrated that Sevo preconditioning has protective effects on lung transplants in both, PGD and AR. The observed amelioration may be attributed to suppressed inflammatory cytokines during PGD and the induction of alternatively activated macrophages during AR. These promising data could set the base for using Sevo preconditioning in donor lungs for a human trial.

Hydatosis is a clinical entity known since the time of Hippocrates with Echinococcus granulosus as most common cause of hydatidosis. Humans as well as herbivores are infected as intermediate hosts and the zoonosis is most commonly observed in the liver and lungs. Intrathoracic extrapulmonary cysts are uncommon. We present the rare presentation of concomitant intrathoracic extrapulmonary and cervical hydatid cysts after a follow-up of 10 years. The patient presented with a soft palpable supraclavivular mass and increasing pain. Thoracoscopic exploration (VATS, video-assisted thoracic surgery) revealed a cystic lesion at the apex of the left hemithorax without contact to the lung. We performed a cystotomy and removed the laminated membrane. Later, the cervical hydatid cyst was removed. Five years later, a recurrence of the disease was again resected. Currently, 10 years after initial referral, the patient remains without any signs of active disease. To our knowledge, this is the first report of an intrathoracic extrapulmonary hydatidosis removed by VATS. Our report presents VATS as a surgical option in the treatment of intrathoracic extrapulmonary hydatid disease of the thoracic apex and confirms the feasibility of minimal invasive surgery for intrathoracic hydatid disease.

Combining neo-adjuvant chemotherapy and surgery is part of multimodality treatment of malignant pleural mesothelioma (MPM), but not all patients benefit from this approach. In this exploratory analysis, we investigated the prognostic value of circulating miR-625-3p and lncRNA GAS5 after neo-adjuvant chemotherapy. 36 MPM patients from the SAKK 17/04 trial (NCT00334594), whose blood was available before and after chemotherapy were investigated. RNA was isolated from plasma and reverse transcribed into cDNA. miR-16-5p and &beta, actin were used as a reference gene for miR-625-3p and GAS5, respectively. After exclusion of samples due to hemolysis or RNA degradation, paired plasma samples from 32 patients before and after chemotherapy were further analyzed. Quantification of miR-625-3p levels in all 64 samples revealed a bimodal distribution and cloning and sequencing of miR-625-3p qPCR product revealed the presence of miR-625-3p isomiRs. Relative change of the circulating miR-625-3p and GAS5 levels after chemotherapy showed that increased circulating miR-625-3p and decreased GAS5 was significantly associated with disease progression (Fisher&rsquo, s test, p = 0.0393). In addition, decreased levels of circulating GAS5 were significantly associated with shorter overall and progression-free survival. Our exploratory analysis revealed a potential value of circulating non-coding RNA for selection of patients likely to benefit from surgery after platinum-based adjuvant chemotherapy.

OBJECTIVES Nonintubated surgical biopsy (NISB) of interstitial lung disease (ILD) has shown promise in unicentre reports as a reliable method to achieve pathological diagnosis with low morbidity. The aim of this study was to investigate for the first time early outcomes of NISB of ILD using a multicentre retrospective analysis. METHODS Seven European and extra-European institutions participated in the study. Overall, 112 procedures were included. The mean age was 60 ± 12 years (65 men and 47 women). Preoperative total lung capacity and diffusion capacity of carbon monoxide were 74 ± 16% predicted and 57 ± 18% predicted, respectively. Forty-five patients had 1 or more associated comorbidities. NISB of ILD were performed under spontaneous ventilation by intercostal block (n = 84) or epidural anaesthesia (n = 28) with (n = 58) or without (n = 54) sedation and by thoracoscopic surgery (n = 88) or minithoracotomy (n = 24). RESULTS Mean anaesthesia time, operative time and global time spent in the operating room were 31 ± 31 min, 29 ± 15 min and 89 ± 156 min, respectively. Feasibility was scored as excellent, good, satisfactory or unsatisfactory requiring conversion to general anaesthesia with intubation in 92, 12, 2 and 6 instances, respectively. There were no deaths. Morbidity was 7.1% and included prolonged air leaks in 4 patients and pneumonia, atelectasis, anaemia and gastric bleeding in 1 patient each. A precise pathological diagnosis was achieved in 108 patients (96%). The mean hospital stay was 2.5 ± 2.7 days. Comparisons of results achieved in the largest single-centre series (group A, 60 patients operated on) versus those resulting from the sum of the patients operated on in the other centres (group B, 52 patients operated on) showed no differences in feasibility (P = 0.10) and morbidity (P = 0.10) whereas hospital stay was shorter in group A (1.3 ± 0.5 days vs 3.9 ± 3.4 days, P

AIM OF THE STUDY Non-intubated, video-assisted thoracoscopic surgery (NiVATS) has been successfully developed in several centres worldwide. Local anaesthesia techniques and techniques to perform thoracoscopic surgery on a spontaneously breathing lung are the two key elements which must be adopted to establish a NiVATS programme. We established NiVATS by performing bilateral, uniportal sympathectomies, and compared it to classical video-assisted thoracoscopic surgery (VATS) under general anaesthesia with double-lumen intubation. METHODS Ten consecutive bilateral VATS sympathectomies were compared with ten consecutive NiVATS procedures. Nineteen of the procedures were for palmar hyperhidrosis and one was for facial blushing. Duration of anaesthesia, surgery and hospitalisation, perioperative complications, side effects and quality of life before and after sympathectomy were analysed. RESULTS Median age was 26.5 years (range 17–55) and mean BMI in the NiVATS group was 21.8 (range 19.1–26.3). NiVATS sympathectomies were performed as outpatient procedures significantly more often (9/10 vs 3/10, p = 0.008). Quality of life was significantly increased after sympathectomy in all patients, with no significant differences between the NiVATS and the VATS groups. There were no differences between the two groups regarding compensatory sweating (40 vs 50%, p = 0.66). The duration of anaesthesia, not including the time required for the surgery, was significantly shorter in the NiVATS group (p

We hypothesize a significant correlation between parameters of preoperative dynamic magnetic resonance imaging (MRI) and postoperative outcomes measured by pulmonary function tests.Dynamic MRI of the lungs was prospectively performed during 2 breath cycles 1 day before and 3 months after surgery, herein termed as pre- and post-lung-volume reduction surgery (LVRS) MRI. Quantitative measurements were performed on sagittal planes for the left lung and right lung: lung height, anteroposterior diameter, hemidiaphragm height and area as well as perimeter. Additionally, dynamic changes in hemidiaphragmatic area and height were measured. Parameters were normalized by patients' height. Pulmonary function test pre-LVRS and post-LVRS was performed. The cut-off value for treatment benefit was defined as a 30% increase in forced expiratory volume in 1 s.Thirty-nine consecutive patients (15 women, median age 61 years) were included. On expiration, the mean lung area on both sides (Pright = 0.001 and Pleft = 0.016) and anteroposterior diameter of the right lung (Pright = 0.003) improved post-LVRS. Dynamic measurements showed differences pre- and post-LVRS on the right lung but not on the left lung (Pright 0.001 and Pleft = 0.090). There were no significant changes in lung height for both sides, in hemidiaphragmatic height on the right as well as diaphragmatic area pre- and post-LVRS (P 0.05). Except for hemidiaphragmatic height on the left lung (P = 0.039), no significant differences were found on inspiration. Considering the 30% cut-off for treatment benefit, the receiver operating curves analysis indicated a height-normalized expiratory lung area ≥35 793 mm2 as the most sensitive preoperative outcome predictor (sensitivity = 86%; specificity = 61%).Preoperative dynamic MRI can be used as an additional outcome predictor for patient selection in LVRS. A height-normalized total lung area in expiration ≥35 793 mm2 correlates with a 30% increase in forced expiratory volume in 1 s.SNCTP000000480.

OBJECTIVES We queried the European Society of Thoracic Surgeons (ESTS) prospective thymic database for descriptive analysis and for comparison with the ESTS retrospective thymic database (1990-2010). METHODS Data were retrieved (January 2007-November 2017) for 1122 patients from 75 ESTS institutions. RESULTS There were 484 (65%) thymomas, 207 (28%) thymic carcinomas and 49 (7%) neuroendocrine thymic tumours. Staging (Masaoka) included 483 (67%) stage I and II, 100 (14%) stage III and 70 (10%) stage IV tumours. The new International Association for the Study of Lung Cancer/International Thymic Malignancies Interest Group tumour, node and metastasis (TNM) classification was available for 224 patients and including 177 (85%) stage I-II, 37 (16%) stage IIIA and 10 (4%) stage IIIB tumours. Chemotherapy as induction and adjuvant treatment was used in 14% and 15% of the patients. Radiotherapy was almost exclusively used postoperatively (24%). A minimally invasive surgical approach (video-assisted thoracic surgery/robotic-assisted thoracic surgery) was used in 276 (33%) patients. The overall recurrence rate was 10.8% (N = 38). Compared to the ESTS retrospective database, the increased prevalence of thymic carcinomas (from 9% to 28%) and neuroendocrine thymic tumours (from 2% to 7%), an increase in the use of minimally invasive techniques (from 6% to 34%) and a wider use of chemotherapy as induction (from 9% to 15%) and adjuvant (from 2% to 16%) treatment were observed in the prospective database. The introduction of a set of variables considered essential for the data use ('minimum dataset') resulted in an increased average completeness rate. CONCLUSIONS The reported data from the ESTS prospective thymic database confirm the recent trends in the management of thymic tumours. The ESTS prospective thymic database represents a powerful resource open to all ESTS members for the global effort to manage these rare tumours.

Background Extracorporeal life support (ECLS) as a bridge to lung retransplantation has been reported only anecdotally. Thus, we analyzed combined data from our center with pooled data from published studies to identify selection criteria for this advanced therapy. Methods Four patients at our center were bridged on ECLS to lung retransplantation. Patient data were retrospectively retrieved from electronic records. The MEDLINE database was searched using the PubMed engine and yielded 13 relevant studies that included a minimum of 3 patients bridged to lung retransplantation, and four studies described detailed data on 17 patients. Patient data from our center (n = 4) were pooled with data from the MEDLINE database (n = 17) and analyzed. Results Of 21 patients, 3 (14%) died on ECLS awaiting retransplantation, and 18 (86%) underwent retransplantation after a median of 37 months (range, 0 to 168 months) after primary transplantation. Type of ECLS was extracorporeal carbon dioxide removal (ECCO2R) in 4, venovenous extracorporeal membrane oxygenation (ECMO) in 7, venoarterial ECMO in 5, or was not mentioned in 2. The 90-day postoperative mortality was 28%. Overall 1-year survival was 48%. Patients bridged to retransplantation with ECCO2R/venovenous ECMO ( p = 0.05) or on awake ECMO ( p = 0.06) showed strong trends toward better survival in univariate analysis. Univariate and multivariate analysis identified a longer intertransplant interval as a statistically significant favorable prognostic factor. In a selected subgroup of patients (awake ECCO2R/venovenous ECMO support and intertransplant interval >2 years), 1-year survival reached 67%. Conclusions Despite limited overall 1-year survival for patients bridged with ECLS to lung retransplantation, careful patient selection may yield an acceptable 1-year survival of 67%.

Reusing tissue of amputated or unsalvageable limbs to reconstruct soft tissue defects is one aspect of the “spare parts concept.” Using a free fillet flap in such situations enables the successful formation of a proximal stump with the length needed to cover a large defect from forequarter amputation without risking additional donor-site morbidity. The use of free fillet flaps for reconstruction after forequarter and traumatic upper extremity amputations is illustrated here in a case report. A 41-year old patient required a forequarter amputation to resect a desmoid tumor, resulting in an extensive soft-tissue defect of the upper extremity. A free fillet flap of the amputated arm and an additional local epaulette flap were used to reconstruct the defect. At 9 months after the procedure, a satisfactory result with a very well healed flap was attained. Free fillet flaps can be used successfully for reconstruction of large upper extremity defects, without risking additional donor-site morbidity.

Background One-lung ventilation during thoracic surgery is associated with hypoxia–reoxygenation injury in the deflated and subsequently reventilated lung. Numerous studies have reported volatile anesthesia–induced attenuation of inflammatory responses in such scenarios. If the effect also extends to clinical outcome is yet undetermined. We hypothesized that volatile anesthesia is superior to intravenous anesthesia regarding postoperative complications. Methods Five centers in Switzerland participated in the randomized controlled trial. Patients scheduled for lung surgery with one-lung ventilation were randomly assigned to one of two parallel arms to receive either propofol or desflurane as general anesthetic. Patients and surgeons were blinded to group allocation. Time to occurrence of the first major complication according to the Clavien-Dindo score was defined as primary (during hospitalization) or secondary (6-month follow-up) endpoint. Cox regression models were used with adjustment for prestratification variables and age. Results Of 767 screened patients, 460 were randomized and analyzed (n = 230 for each arm). Demographics, disease and intraoperative characteristics were comparable in both groups. Incidence of major complications during hospitalization was 16.5% in the propofol and 13.0% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.75; 95% CI, 0.46 to 1.22; P = 0.24). Incidence of major complications within 6 months from surgery was 40.4% in the propofol and 39.6% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.95; 95% CI, 0.71 to 1.28; P = 0.71). Conclusions This is the first multicenter randomized controlled trial addressing the effect of volatile versus intravenous anesthetics on major complications after lung surgery. No difference between the two anesthesia regimens was evident.

Lung transplantation (LTx) is an accepted therapy in children with end-stage lung diseases. Pediatric-specific experience is considered important in pediatric LTx. We present our institutional experience and its outcome since the year 2000, asking whether different treatment strategies produce comparable outcomes in pediatric lung transplant recipients at our predominantly adult center. This is a retrospective analysis of children and adolescents aged ≤20 years, undergoing LTx between January 2001 and December 2013. Minimum follow-up was 12 months. Primary endpoints were re-transplantation or death. We performed 33 lung transplant procedures in 29 patients. Survival 1 month post-operatively was 96.6%, at 3 months 93.1% and at 12 months 82.8%, respectively. At the end of our follow up, 72.4% of our pediatric cohort was still alive - median post-transplant survival was 59 months (range 0-159). 72.4% of the children were transplanted with support of extracorporeal membrane oxygenation (ECMO), size-reduced donor grafts were used in 69.0%. The differences between post-transplant survival of the "non-ECMO-group" versus the "ECMO-group" (137 vs. 28 months, P=0.7) and "full size" versus "size-reduced bilateral transplants" (61 vs. 28 months, P = 0.7) were not significant, though. There were no anastomotic complications, also not in size-reduced lungs. Our results are well comparable to the international data and show excellent short- and mid-term outcomes. We advocate ECMO-bridge to be considered as a valuable treatment option to prolong time on the waiting list in highly selected patients, as well as size reduction and lobar transplants as a strong strategy to increase the donor pool and reduce donor-recipient size-mismatches. Pediatr Pulmonol. 2016;51:1222-1228. © 2016 Wiley Periodicals, Inc.

OBJECTIVES To analyse the relapse pattern and influence of second-line treatment after recurrence of malignant pleural mesothelioma (MPM) in patients who had previously undergone multimodality treatment. METHODS Between September 1999 and December 2013, 136 patients underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy after induction chemotherapy for MPM. We analysed 106 patients who presented with recurrent disease until October 2014. Data were retrieved from our mesothelioma database, with additional information regarding precise localization gathered by reviewing the imaging and medical records. RESULTS The overall recurrence rate was 78% (106/136 patients). The median freedom from recurrence was 9 months after surgery [95% confidence interval (95% CI) 7-10]. Local recurrence only was observed in 33 patients (31%), distant metastases only in 27 patients (26%) and simultaneous distant and local recurrence in 46 patients (43%). Local recurrence was observed significantly less frequently in patients having received adjuvant radiotherapy (19 vs 47%, P = 0.003), but there was no significant impact on overall survival (OS) [radiation: 22 months (95% CI 19-24); no-radiation: 23 months (95% CI 18-27), P = 0.6]. The median OS was 22 months (95% CI 21-24), median post-recurrence survival (PRS) was 7 months (95% CI 5-9) and patients with local recurrence only survived significantly longer (12 months, 95% CI 8-16) compared with patients with distant recurrence only (5 months, 95% CI 2-8) or distant plus local relapse (6 months, 95% CI 3-9; P = 0.04). A total of 78 patients received a second-line therapy after tumour recurrence: chemotherapy (n = 48), local radiotherapy (n = 9), surgery (n = 10) or a combination thereof (n = 11). Patients undergoing second-line treatment survived significantly longer compared with patients not receiving therapy (P < 0.0005). The median PRS after surgery was significantly longer than that of patients receiving chemo-, radio- or chemo-radiotherapy (P = 0.04). CONCLUSIONS Local recurrence of MPM remains the most frequent type of relapse even after multimodality treatment including MCR. In the present cohort, active treatment seems beneficial to the patient since surgical excision of local tumour relapse has good long-term outcome in selected patients. Thus, second-line treatment may prolong PRS; however, these results need to be confirmed in a prospective manner.

Lung volume reduction surgery improves exercise tolerance, lung function, and quality of life for selected patients with emphysema. Lung volume reduction surgery is well established for patients in a highly elective setting. It is, however, contraindicated in cases of acute cardiorespiratory failure. We present the case of a patient with severe emphysema who had acute respiratory failure and decompensated cor pulmonale requiring life-saving venovenoarterial extracorporeal life support after admission to the emergency unit. He underwent lung volume reduction surgery with intent to wean from extracorporeal life support. He had complete functional recovery after 4 months.

Objectives Intracavitary chemotherapy is a promising concept to improve local tumor control for malignant pleural mesothelioma with reported high morbidity rates. We have demonstrated that administration of cisplatin loaded to fibrin increased local drug concentration and reduced systemic toxicity in preclinical models. We present a phase I trial of intracavitary cisplatin-fibrin after surgical tumor resection. Methods A total of 12 patients (75% International Mesothelioma Interest Group stage III-IV) were treated with 4 dose levels of intracavitary cisplatin-fibrin (11-44 mg/m2 body surface area) in a dose-escalating design. Cisplatin-fibrin was sprayed on the resected surfaces after pleurectomy/decortication. Blood and tissue samples were taken to assess toxicity and pharmacokinetics. Patients were regularly followed up. Results No dose-limiting toxicity was observed. Major morbidity occurred in 4 patients (33%). The 30-day and 90-day mortality were both 0%. Of 80 adverse events, 9 were classified serious, but none of these were related to study treatment. Local cisplatin concentration in the chest wall tissue was high at all dose levels (median, 46.3 μg/g [12-133 μg/g]). In serum, median cisplatin area under the concentration time curve values were always below renal toxicity levels. The median overall survival with 95% confidence interval was 21 months (10-31 months). In 1 patient with epithelioid malignant pleural mesothelioma (International Mesothelioma Interest Group stage I), there was no sign of relapse 48 months after treatment (44 mg/m2 body surface area). Conclusions The administration of intracavitary cisplatin-fibrin is safe with favorable pharmacokinetics. Although most patients had advanced disease, long-term outcomes are comparable to other multimodal concepts. A confirmation phase II trial is ongoing.

Purpose: Utilization of donation after circulatory death (DCD) donors has the potential to decrease donor shortage in lung transplantation (LTx). This study reviews the long-term outcome of LTx from DCD donors. Methods: We included all consecutive DCD (Maastricht Category III) and all donations after brain death (DBD) donor lung transplants at our Center performed between January 2012 and February 2017. Data were analyzed comparing the two groups in regard of survival after LTx as primary outcome. Results: Median withdrawal to cardiac arrest time was 17 min (interquartile range [IQR]: 11.5–20.5). Median cardiac arrest to cold perfusion was 32 min (IQR: 24.5–36.5). Primary graft dysfunction (PGD) grade 3 at T72 occurred in three recipients. Chronic lung allograft dysfunction (CLAD) led to death in two cases. In DCD group, there was no 90-day mortality. In DCD, group 1- and 3-year survival rates were 100% and 80%. In DBD group, 1- and 3-year survival rates were 85% and 69% (p = 0.4). Conclusions: Our report confirmed the comparable outcome from DCD donors compared with DBD donors. Utility of DCD donors is a safe option to overcome donor shortage.

The aim of lung volume reduction surgery (LVRS) for patients suffering from severe emphysema is to improve lung function and palliate dyspnea. Careful patient selection in a multidisciplinary approach in a high-volume center is mandatory for a successful outcome. Pulmonary complications including air leak and pneumonia as well as cardiac complications are the most common complications after LVRS. The following article will focus on most common complications observed after LVRS and review the management strategies to improve surgical outcome.

We present an exemplary case of an immunocompromised patient with pulmonary mucormycosis successfully treated by a combination of surgical removal of the mucor and urokinase to control the recurring hemothorax. The use of urokinase in hemothoraces is a way to reduce repetitive surgeries in weak patients.

Background Ex vivo lung perfusion (EVLP) improved the process of donor-lung management. Cytokine accumulation during EVLP has been shown to correlate with a worse outcome after lung transplantation. Our objective was to test the safety and efficacy of cytokine filtration during EVLP in a large animal model. Methods Pig donor lungs were preserved for 24 hours at 4°C, followed by 12 hours of EVLP according to the Toronto protocol. The perfusate was continuously run through an absorbent device (CytoSorb ® ) via a veno-venous shunt from the reservoir in the filter group. EVLP was performed according to the standard protocol in the control group (n = 5 each). EVLP physiology, lung X-ray, perfusate biochemistry, inflammatory response, and microscopic injury were assessed. Results Cytokine filtration significantly improved airway pressure and dynamic compliance during the 12-hour perfusion period. Lung X-rays acquired at the end of perfusion showed increased consolidation in the control group. Electrolyte imbalance, determined by increased hydrogen, potassium, and calcium ion concentrations in the perfusate, was markedly worsened in the control group. Glucose consumption and lactate production were markedly reduced, along with the lactate/pyruvate ratio in the filter group. Cytokine expression profile, tissue myeloperoxidase activity, and microscopic lung injury were significantly reduced in the filter group. Conclusions Continuous perfusate filtration through sorbent beads is effective and safe during prolonged EVLP. Cytokine removal decreased the development of pulmonary edema and electrolyte imbalance through the suppression of anaerobic glycolysis and neutrophil activation in this setting. Further studies are needed to test the beneficial effect of cytokine filtration on post-transplant lung function.

Background: Studies have shown that survival after lung transplantation is impaired if extracorporeal membrane oxygenation (ECMO) support is implemented. We investigated the outcome and potential independent risk factors on survival in recipients undergoing lung transplantation with intraoperative ECMO support. Materials and methods: Medical records of recipients were retrospectively evaluated (January 2000-December 2014). Retransplantation and bridge to transplantation on ECMO were excluded. Recipients (n = 291) were divided into 2 groups: those who needed intraoperative ECMO support (Group 1, n = 134) and those who did not receive intraoperative ECMO support (Group 2, n = 157). Independent risk factors were identified by a stepwise backward regression analysis. Results: 1-year survival was 84.2% in Group 1 vs. 90.4% in Group 2, and 5-year survival was 52.8% in Group 1 vs. 70.5% in Group 2 (p = 0.002). Multivariate analysis indicated that recipient age (p = 0.001), renal replacement therapy (p = 0.001) and intraoperative ECMO support (p = 0.03) were significant risk factors for overall survival. The rate of postoperative early surgical complications was comparable between the two groups (p = 0.09). The number of patients requiring renal replacement therapy and experiencing late pulmonary complications was significantly higher in Group 1 (p = 0.02). Conclusions: Our data showed that lung transplantation with intraoperative ECMO support is associated with poor outcomes.

Objectives Lung volume reduction surgery (LVRS) and lung transplantation (LTx) are the treatments of choice in selected patients with end-stage emphysema. Recently, the history of LVRS has been questioned due to reduced post-transplant survival. We aim to address this question by reviewing our experience, which is the largest single-centre series of LVRS followed by LTx. Methods We reviewed our prospectively recorded database in patients with emphysema undergoing LTx between 1993 and 2014. Preoperative workup and postoperative outcomes were compared according to previous LVRS status. The Kaplan-Meier test was used for survival analysis and compared with a log-rank test. Results One hundred and seventeen patients (66 men; mean age 56 ± 7 years) underwent LTx during the study period, 52 of whom had previous LVRS (LVRS + LTx). The mean time from LVRS to LTx was 45 ± 31 months. Patients were slightly older and had extensive smoking history in the LVRS + LTx group. Overall, in-hospital mortality was 10%, which did not differ significantly regardless of the history of LVRS (P = 0.8). The median survival for the LTx-only and LVRS + LTx groups was 86 [95% confidence interval (CI) 56-116] and 107 (95% CI 77-137) months, respectively (P = 0.6). Conclusions Previous LVRS does not negatively affect short-term and long-term outcomes following LTx in patients with end-stage emphysema. The history of LVRS should not preclude the candidacy for LTx. Considering the limited number of donors available, the LVRS option should be kept in mind for the postponement of LTx in carefully selected patients.

Purpose Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease, for which the underlying pathophysiological mechanisms have yet to be fully elucidated. In recent years, microRNAs have emerged as important players in regulation of physiological processes, and dysregulation of microRNA expression has been linked to various diseases. So far, only a limited number of studies has investigated microRNAs in CTEPH. Therefore, the aim of this study was to investigate whether microRNAs are also detectable in tissue specimens obtained from patients undergoing pulmonary endarterectomy (PEA), since differential expression in the tissues could suggest a role of these microRNAs in disease development. Methods Tissue specimens were obtained from patients 16 patients undergoing PEA at the University Hospital Zurich, between 2016 and September 2018. RNA was extracted from FFPE blocks, and expression levels of three microRNAs identified as potential players in CTEPH development through a study of circular RNAs (Miao et al, Medicine 2017), miR-939, miR-942 and miR-92a-2-5p, were measured by microRNA-specific RT-qPCR. In addition, miR-210, the most important microRNA in regulation of hypoxia was measured. Expression of microRNAs was correlated to various clinical factors. Results Of the three miR-candidates measured in plasma before, miR-939 and miR-942 were detectable in PEA tissue specimens. In addition, the hypoxamiR miR-210 was also detectable and represented the microRNA with the highest expression levels. Expression of miR-939 showed a significant negative correlation with peripheral oxygen saturation (p=0.03; Spearman's R=-0.548) and pulmonary vascular resistance (p=0.05, R=-0.502), while miR-942 expression negatively correlated with Jamieson Classification (p=0.04, R=-0.623). Conclusion This pilot study has shown for the first time that microRNAs are readily detectable in material extracted during PEA. Our data shows that microRNAs are differentially expressed between different patients, and that microRNA expression is correlated with various factors of clinical presentation. Thus, our data highlight that microRNA expression warrants further investigation as their dysregulation might be involved in the development of CTEPH.

OBJECTIVES Primary graft dysfunction (PGD) is a major cause of mortality within the first year following lung transplantation. Pulmonary hypertension, elevated body mass index (BMI), prolonged ischaemic time of the graft, intraoperative blood transfusions >1000 ml and the use of cardiopulmonary bypass or extracorporeal membrane oxygenation increase the risk for PGD. We aimed to evaluate whether dyslipidaemia is an additional risk factor for the development of PGD. METHODS We retrospectively analysed demographic and clinical data of 264 patients who received their first bilateral lung transplantation between March 2000 and October 2013 at our institution. The endpoint was PGD grade 3 at any time, defined according to the International Society for Heart and Lung Transplantation (ISHLT) criteria. Fasting lipid profiles at listing time or just before transplantation (baseline) were documented and dyslipidaemia was defined as any of the parameters being out of range. Comparisons of continuous variables between patients with PGD grade 3 and patients without were performed with the Mann-Whitney U-test, whereas proportions were compared with the χ2 test. Continuous variables were presented as arithmetic means with standard deviation for ease of comparison, but levels of statistical significance were computed using the appropriate non-parametric statistical test. To identify PGD risk factors, a forward stepwise logistic regression model was used. RESULTS PGD occurred in 63 recipients (24%). Pretransplant dyslipidaemia was documented in 153 recipients (58%) and was significantly more prevalent among recipients developing PGD (45 vs 108, P < 0.013). Despite various underlying pulmonary pathologies, higher triglyceride (TG) levels (1.41 ± 0.78 vs 1.16 ± 0.78, P < 0.012), lower high-density lipoprotein-cholesterol (HDL-C) concentrations (1.24 ± 0.55 vs 1.57 ± 0.71, P < 0.0005) and higher cholesterol/HDL-C values (3.80 ± 2.02 vs 3.00 ± 0.92, P < 0.0005) were associated with a lower incidence of PGD. Patients with PGD had significantly longer ischaemic time (350 ± 89 vs 322 ± 91, P = 0.017) and higher BMI (23 ± 5 vs 21 ± 4.4, P < 0.007). CONCLUSIONS Dyslipidaemia seems to be an independent risk factor for PGD after lung transplantation: low circulating levels of HDL-C and hypertriglyceridaemia increase the incidence of PGD. Even if HDL-C levels are difficult to alter today, triglyceride and cholesterol levels can be addressed therapeutically and may have a positive influence on the development of PGD.

Summary Background Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. Methods We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1–3 N0–2, M0; WHO performance status 0–1; age 18–70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m 2 and pemetrexed 500 mg/m 2 on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0–1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0–1 vs N2), and T stage (T1–2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. Findings We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32–66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8–56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5–10·7) in the no radiotherapy group and 9·4 months (6·5–11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. Interpretation Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. Funding Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

Introduction Treatment of malignant pleural mesothelioma (MPM) remains a clinical challenge. The aim of this study was to identify selection factors for allocation of MPM patients to multimodal therapy based on survival data from 12 years of experience. Methods Eligible patients had MPM of all histological subtypes with clinical stage T1–3 N0–2 M0. Induction chemotherapy consisted of cisplatin/gemcitabine (cis/gem) or cisplatin/pemetrexed (cis/pem), followed by extrapleural pneumonectomy (EPP). Multivariate analysis was performed to assess independent prognosticators for overall survival (OS). A Multimodality Prognostic Score was developed based on clinical variables available before surgery. Results From May 1999 to August 2011, 186 MPM patients were intended to be treated with induction chemotherapy followed by EPP. Hematologic toxicity was significantly less frequent after cis/pem compared to cis/gem, but there was no difference in response or OS between the regimens. One hundred and twenty-eight patients underwent EPP with a 30-day mortality of 4.7%. Fifty-two percent of the patients received adjuvant radiotherapy. The median OS of patients undergoing EPP was significantly longer with 22 months (95% confidence interval: 20–24) when compared to 11 months (9–12) for patients treated without EPP. A prognostic score was defined considering tumor volume, histology, c-reactive protein level, and response to chemotherapy that identified patient groups not benefitting from multimodality treatment which was confirmed in an independent cohort. Conclusion Patients receiving induction chemotherapy followed by EPP for MPM of all histological subtypes and irrespective of nodal status showed a median survival of 22 months. A prognostic score is proposed to help patient allocation for surgery after validation in an independent cohort.