Short-chain fatty acids induced lung tumor cell death and increased peripheral blood CD4+ T cells in NSCLC and control patients ex vivo.

Background: Despite therapy advances, one of the leading causes of cancer deaths still remains lung cancer. To improve current treatments or prevent non-small cell lung cancer (NSCLC), the role of the nutrition in cancer onset and progression needs to be understood in more detail. While in colorectal cancer, the influence of local microbiota derived SCFAs have been well investigated, the influence of SCFA on lung cancer cells via peripheral blood immune system should be investigated more deeply. In this respect, nutrients absorbed via the gut might affect the tumor microenvironment (TME) and thus play an important role in tumor cell growth. Objective: This study focuses on the impact of the short-chain fatty acid (SCFA) Sodium Butyrate (SB), on lung cancer cell survival. We previously described a pro-tumoral role of glucose on A549 lung adenocarcinoma cell line. In this study, we wanted to know if SB would counteract the effect of glucose and thus cultured A549 and H520 in vitro with and without SB in the presence or absence of glucose and investigated how the treatment with SB affects the survival of lung cancer cells and its influence on immune cells fighting against lung cancer. Methods: In this study, we performed cell culture experiments with A549, H520 and NSCLC-patient-derived epithelial cells under different SB levels. To investigate the influence on the immune system, we performed in vitro culture of peripheral mononuclear blood cells (PBMC) from control, smoker and lung cancer patients with increasing SB concentrations. Results: To investigate the effect of SB on lung tumor cells, we first analyzed the effect of 6 different concentrations of SB on A549 cells at 48 and 72 hours cell culture. Here we found that, SB treatment reduced lung cancer cell survival in a concentration dependent manner. We next focused our deeper analysis on the two concentrations, which caused the maximal reduction in cell survival. Here, we observed that SB led to cell cycle arrest and induced early apoptosis in A549 lung cancer cells. The expression of cell cycle regulatory proteins and A549 lung cancer stem cell markers (CD90) was induced. Additionally, this study explored the role of interferon-gamma (IFN-γ) and its receptor (IFN-γ-R1) in combination with SB treatment, revealing that, although IFN-γ-R1 expression was increased, IFN-γ did not affect the efficacy of SB in reducing tumor cell viability. Furthermore, we examined the effects of SB on immune cells, specifically CD8+ T cells and natural killer (NK) cells from healthy individuals, smokers, and NSCLC patients. SB treatment resulted in a decreased production of IFN-γ and granzyme B in CD8+ T cells and NK cells. Moreover, SB induced IFN-γ-R1 in NK cells and CD4+ T cells in the absence of glucose both in PBMCs from controls and NSCLC subjects. Conclusion: Overall, this study highlights the potential of SB in inhibiting lung cancer cell growth, triggering apoptosis, inducing cell cycle arrest, and modulating immune responses by activating peripheral blood CD4+ T cells while selectively inducing IFN-γ-R1 in NK cells in peripheral blood and inhibiting peripheral blood CD8+ T cells and NK cells. Thus, understanding the mechanisms of action of SB in the TME and its influence on the immune system provide valuable insights of potentially considering SB as a candidate for adjunctive therapies in NSCLC.

Managing One-Lung Ventilation in Tracheostomized Patients: A 6-Year Retrospective Analysis.

BACKGROUND: To ensure safe and optimal surgical conditions in thoracic surgery, one-lung ventilation is crucial. Various techniques exist to achieve one-lung ventilation. Tracheotomized patients who require one-lung ventilation represent a unique and rare subgroup that demands specialized knowledge and skills. The very limited literature has discussed alternative methods, no randomized controlled trials have addressed this issue yet. METHODS: We performed a retrospective analysis of patients who underwent one-lung ventilation in the Department of Thoracic Surgery of a German University Hospital between 2016 and 2021. The study assessed patient demographics, airway management techniques, ventilation parameters, and adverse events. RESULTS: In 3,197 anesthesia procedures during the observation period, 152 patients had an existing tracheostomy, of which 56 required one-lung ventilation. Among others in 42 cases, a tracheostomy tube was combined with a bronchial blocker, and in 10 cases, a double-lumen tracheostomy tube was used. There were no severe complications. Intraoperative dislocations that required repositioning of the device occurred in six patients (13.3%) with bronchial blockers and one patient with double-lumen tracheostomy tube (10%). CONCLUSION: The management of one-lung ventilation in tracheotomized patients presents unique challenges. While double-lumen tracheostomy tubes have specific advantages, we recommend considering their use carefully. For most tracheotomized patients, bronchial blockers in conjunction with a tracheostomy tube are used, which offers safety and practicality, irrespective of the tracheostomy's age or type. Further research and randomized controlled trials are warranted to establish best practices for one-lung ventilation in this unique patient population.

Video double-lumen tube for one lung ventilation: implementation and experience in 343 cases of routine clinical use during the first 20 months of the SARS-CoV-2 pandemic.

BACKGROUND: Double-lumen tubes (DLTs) are the preferred device for lung isolation. Conventional DLTs (cDLT) need a bronchoscopic position control. Visualisation of correct DLT positioning could be facilitated by the use of a video double-lumen tube (vDLT). During the SARS-CoV-2-pandemic, avoiding aerosol-generation was suggesting using this device. In a large retrospective series, we report both general and pandemic related experiences with the device. METHODS: All anesthesia records from patients aged 18 years or older undergoing surgery from April 1st, 2020 to December 31st, 2021 in the department of thoracic surgery requiring intraoperative lung isolation were analyzed retrospectively. RESULTS: During the investigation period 343 left-sided vDLTs (77.4%) and 100 left-sided cDLTs (22.6%) were used for one lung ventilation. In the vDLT group bronchoscopy could be reduced by 85.4% related to the cDLT group. Additional bronchoscopy to reach or maintain correct position was needed in 11% of the cases. Other bronchoscopy indications occured in 3.6% of the cases. With cDLT, in 1% bronchoscopy for other indications than conforming position was observed. CONCLUSIONS: The Ambu® VivaSight™ vDLT is an efficient, easy-to-use and safe airway device for the generation of one lung ventilation in patients undergoing thoracic surgery. The vDLT implementation was achieved easily with full interchangeability to the left-sided cDLT. Using the vDLT can reduce the need for aerosol-generating bronchoscopic interventions by 85.4%. Continuous video view to the carina enabling position monitoring of the DLT without need for bronchoscopy might be beneficial for both employee's and patient's safety.

Interdisciplinary Treatment of Malignant Chest Wall Tumors.

BACKGROUND: Chest wall resections for malignant chest wall tumors (MCWTs), particularly those with full-thickness chest wall involvement requiring reconstruction, present a therapeutic challenge for thoracic and plastic reconstructive surgeons. The purpose of this study was to review our experience with chest wall resection for primary and metastatic MCWTs, with a focus on perioperative outcomes and postoperative overall survival (OS). METHODS: All patients who underwent surgical resection for primary and secondary MCWTs at our single institution between 2000 and 2019 were retrospectively analyzed. RESULTS: A total of 42 patients (25 male, median age 60 years) operated upon with curative (n = 37, 88.1%) or palliative (n = 5, 11.9%) intent were reviewed. Some 33 (78%) MCWTs were of secondary origin. Chest wall reconstruction was required in 40 (95%) cases. A total of 13 (31%) patients had postoperative complications and one (2.3%) died perioperatively. The 5-year postoperative overall survival rate was 51.9%. The postoperative 5-year survival rate of 42.6% in patients with secondary MCWTs was significantly lower compared to the figure of 87.5% in patients with primary MCWTs. CONCLUSIONS: In well-selected patients, chest wall resections for primary and secondary MCWTs are feasible and associated with good perioperative outcomes. For secondary MCWTs, surgery can also be performed with palliative intent.

Contribution of serum lipids and cholesterol cellular metabolism in lung cancer development and progression.

Neoplasms of the lungs are the leading cause of cancer incidence and mortality worldwide. Although immunotherapy has increased the overall survival of patients with lung cancer, there is the need to improve this treatment. At this regard, blood lipid levels are thought to be linked to cancer risk and thus a preventive intervention through regulation of the nutrition of patients with lung cancer is gaining much attention. In this study, we therefore asked about the contribution of serum lipids and cholesterol cellular metabolism in lung cancer development and progression. We measured different serum lipids and analyzed cholesterol synthesis enzymes 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) and acetyl-coenzyme A cholesterol acetyltransferase 1 (ACAT1) as well as the cholesterol cellular export protein ATP-binding cassette (ABC) A-1 mRNA by quantitative PCR (qPCR) in the control and tumoral regions of post-surgery lung tissues to analyze the accumulation of cholesterol in cancer cells in a cohort of patients with lung adenocarcinoma (LUAD). We found that triglycerides in serum directly correlated with the body mass index (BMI) in patients with LUAD. By contrast, we found that high-density lipoprotein (HDL) cholesterol inversely correlated with the BMI, C-reactive protein (CRP) and overall survival and total cholesterol inversely correlated with the tumor diameter, serum CRP and overall survival in these LUAD patients. Functionally, the role of cholesterol is indispensable for the growth and development of normal animal cells where it is tightly regulated. Excess of cellular cholesterol regulated by HMGCR is converted to cholesteryl esters by the enzyme ACAT1 and exported extracellularly by the cholesterol transporter ABCA1. Here we found HMGCR and ACAT1 upregulated and ABCA1 downregulated in the lung's tumoral region of our LUAD cohort, indicating cholesterol dysregulated cellular export in lung tumor cells.

Spread through Air Spaces (STAS) in Solitary Pulmonary Metastases from Colorectal Cancer (CRC).

BACKGROUND: Spread through air spaces (STAS) is a recently described route of tumor invasion associated with poor prognosis in primary lung cancer. Aim of this study was to investigate the presence of STAS and to assess its prognostic significance in patients undergoing pulmonary metastasectomy (PM) for solitary metastases from colorectal cancer (CRC). MATERIALS AND METHODS: All 49 CRC patients (30 male and 19 female, median age 66 years) who underwent PM between January 2008 and December 2015 were retrospectively analyzed. RESULTS: STAS was identified in 26.5% (n = 13) of resected specimens. Location of pulmonary lesions (central vs. peripheral) was assessed based on the available computed tomography imaging (n = 47, 96%). STAS was detected in all five patients with central metastases (100%) versus 7 of 42 (17%) with peripheral metastases (p = 0.0001). Locoregional recurrence occurred in STAS-positive patients (n = 4 of 13 vs. n = 0 of 36), all STAS-negative patients remained recurrence-free (p = 0.003). Median number of alveoli with STAS involvement was four (range from 2 to 9). There was statistically positive relationship between the number of alveoli invaded with STAS and locoregional recurrence of metastases (p = 0.0001). The presence of STAS is not a factor affecting the 5-year overall survival rate (p = 0.6651). CONCLUSION: We identified STAS as a frequent finding in resected CRC lung metastases and found insignificant association with outcome.

Glucose-Restricted Diet Regulates the Tumor Immune Microenvironment and Prevents Tumor Growth in Lung Adenocarcinoma.

Background: Lung cancer is the second common cancer type in western countries and has a high mortality. During the development and progression of the tumor, the nutrients in its environment play a central role. The tumor cells depend crucially on glucose metabolism and uptake. Tumor cell metabolism is dominated by the Warburg effect, where tumor cells produce large amounts of lactate from pyruvate under aerobic conditions. We thus reasoned that, reducing carbohydrates in the diet might support anti-tumoral effects of current immunotherapy and additionally target tumor immune escape. Objectives: The link between reducing carbohydrates to improve current immunotherapy is not clear. We thus aimed at analyzing the effects of different glucose levels on the tumor development, progression and the anti-tumoral immune response. Methods: We correlated the clinical parameters of our LUAD cohort with different metabolic markers. Additionally, we performed cell culture experiments with A549 tumor cell line under different glucose levels. Lastly, we investigated the effect of low and high carbohydrate diet in an experimental murine model of lung cancer on the tumor progression and different immune subsets. Results: Here we found a positive correlation between the body mass index (BMI), blood glucose levels, reduced overall survival (OS) and the expression of Insulin-like growth factor-1 receptor (IGF1R) in the lung tumoral region of patients with lung adenocarcinoma (LUAD). Furthermore, increasing extracellular glucose induced IGF1R expression in A549 LUAD cells. Functional studies in a murine model of LUAD demonstrated that, glucose restricted diet resulted in decreased tumor load in vivo. This finding was associated with increased presence of lung infiltrating cytotoxic CD8+ T effector memory (TEM), tissue resident memory T (TRM) and natural killer cells as well as reduced IGFR mRNA expression, suggesting that glucose restriction regulates lung immunity in the tumor microenvironment. Conclusions: These results indicate that, glucose restricted diet improves lung immune responses of the host and suppresses tumor growth in experimental lung adenocarcinoma. As glucose levels in LUAD patients were negatively correlated to postoperative survival rates, glucose-restricted diet emerges as therapeutic avenue for patients with LUAD.

IL-9 Producing Tumor-Infiltrating Lymphocytes and Treg Subsets Drive Immune Escape of Tumor Cells in Non-Small Cell Lung Cancer.

Although lung cancer is the leading cause of cancer deaths worldwide, the mechanisms how lung cancer cells evade the immune system remain incompletely understood. Here, we discovered IL-9-dependent signaling mechanisms that drive immune evasion in non-small cell lung cancer (NSCLC). We found increased IL-9 and IL-21 production by T cells in the tumoral region of the lung of patients with NSCLC, suggesting the presence of Th9 cells in the lung tumor microenvironment. Moreover, we noted IL-9 producing Tregs in NSCLC. IL-9 target cells in NSCLC consisted of IL-9R+ tumor cells and tumor-infiltrating lymphocytes. In two murine experimental models of NSCLC, and in vitro, IL-9 prevented cell death and controlled growth of lung adenocarcinoma cells. Targeted deletion of IL-9 resulted in successful lung tumor rejection in vivo associated with an induction of IL-21 and reduction of Treg cells. Finally, anti-IL-9 antibody immunotherapy resulted in suppression of tumor development even in established experimental NSCLC and was associated with reduced IL-10 production in the lung. In conclusion, our findings indicate that IL-9 drives immune escape of lung tumor cells via effects on tumor cell survival and tumor infiltrating T cells. Thus, strategies blocking IL-9 emerge as a new approach for clinical therapy of lung cancer.

Pleural Resident Macrophages and Pleural IRA B Cells Promote Efficient Immunity Against Pneumonia by Inducing Early Pleural Space Inflammation.

Airway infection is a major cause of mortality worldwide. The identification of new mechanisms aiding in effective host immune response is therefore required. Here, we show that the specific depletion of the pleural immune cell compartment during bacterial pneumonia resulted in a reduced pulmonary immune response and increased mortality in mice. Bacterial airway infection provoked early pleural space (PS) inflammation characterized by innate response activator (IRA) B cell development and pleural large resident macrophage (LRM) necroptosis, the repopulation of LRMs being driven by cellular proliferation in situ. Necroptotic LRMs amplified PS inflammation by stimulating pleural Mincle-expressing macrophages whereas IRA B cells contributed partially to GM-CSF-induced PS inflammation. Upon pulmonary infection, the induction of PS inflammation resulted in reduced bacterial burden whereas the specific depletion of pleural resident macrophages led to increased mortality and bacterial burden and reduced pulmonary immunity. Moreover, mice in which B cells were unable to produce GM-CSF exhibited reduced CD103+ dendritic cells and reduced CD4+ T cell numbers in the draining lymph node. Altogether, our results describe a previously unrecognized mechanism of pleural space inflammation necessary for effective protection against bacterial airway infection.

MET Amplification in Non-Small Cell Lung Cancer (NSCLC)-A Consecutive Evaluation Using Next-Generation Sequencing (NGS) in a Real-World Setting.

In non-small cell lung cancer (NSCLC), approximately 1-3% of cases harbor an increased gene copy number (GCN) of the MET gene. This alteration can be due to de novo amplification of the MET gene or can represent a secondary resistance mechanism in response to targeted therapies. To date, the gold standard method to evaluate the GCN of MET is fluorescence in situ hybridization (FISH). However, next-generation sequencing (NGS) is becoming more relevant to optimize therapy by revealing the mutational profile of each NSCLC. Using evaluable n = 205 NSCLC cases of a consecutive cohort, this study addressed the question of whether an amplicon based NGS assay can completely replace the FISH method regarding the classification of MET GCN status. Out of the 205 evaluable cases, only n = 9 cases (43.7%) of n = 16 high-level MET amplified cases assessed by FISH were classified as amplified by NGS. Cases harboring a MET GCN > 10 showed the best concordance when comparing FISH versus NGS (80%). This study confirms that an amplicon-based NGS assessment of the MET GCN detects high-level MET amplified cases harboring a MET GCN > 10 but fails to detect the various facets of MET gene amplification in the context of a therapy-induced resistance mechanism.

Surgery for Pulmonary Metastases: Long-Term Survival in 281 Patients.

BACKGROUND: Despite weak evidence, pulmonary metastasectomy (PM) is widely performed with intent to improve patient survival. Our single-institution analysis aims to evaluate outcomes and to identify factors influencing survival of patients undergoing PM for metastases from wide range of primary tumors. MATERIALS AND METHODS: All patients undergoing curative-intent PM between 2008 and 2018 were retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on overall survival (OS) was evaluated using univariable and multivariable Cox proportional hazard models. Cutoff values of continuous variables were determined by a receiver operating characteristic analysis. RESULTS: In this study, 281 patients (178 male, median age 61 years) underwent PM. Two (0.7%) perioperative deaths and 23 (8.2%) major complications occurred. Median interval between the treatment of primary tumor and PM was 21 months. Median size of largest metastasis was 1.4 cm. After the median follow-up of 29 months, 134 patients (47.7%) had died. Five-year OS rate after first PM was 47.1%. Complete resection was achieved in 274 (97.5%) patients. Multivariable analysis identified genitourinary origin (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.15-0.60, p = 0.0008) as independent positive survival prognosticator; incomplete resection (HR: 3.53, 95% CI: 1.40-8.91, p = 0.0077) and age at PM of ≥66 years (HR: 1.97, 95% CI: 1.36-2.85, p = 0.0003) were negative prognosticators. CONCLUSION: The use of PM as a part of multimodal treatment is in selected population justified. Our analysis identified age, primary tumor origin, and completeness of resection as independent survival prognosticators.

Gene Expression in Solitary Fibrous Tumors (SFTs) Correlates with Anatomic Localization and NAB2-STAT6 Gene Fusion Variants.

Solitary fibrous tumors (SFTs) harbor recurrent NAB2-STAT6 gene fusions, promoting constitutional up-regulation of oncogenic early growth response 1 (EGR1)-dependent gene expression. SFTs with the most common canonical NAB2 exon 4-STAT6 exon 2 fusion variant are often located in the thorax (pleuropulmonary) and are less cellular with abundant collagen. In contrast, SFTs with NAB2 exon 6-STAT6 exon 16/17 fusion variants typically display a cellular round to ovoid cell morphology and are often located in the deep soft tissue of the retroperitoneum and intra-abdominal pelvic region or in the meninges. Here, we employed next-generation sequencing-based gene expression profiling to identify significant differences in gene expression associated with anatomic localization and NAB2-STAT6 gene fusion variants. SFTs with the NAB2 exon 4-STAT6 exon 2 fusion variant showed a transcriptional signature enriched for genes involved in DNA binding, gene transcription, and nuclear localization, whereas SFTs with the NAB2 exon 6-STAT6 exon 16/17 fusion variants were enriched for genes involved in tyrosine kinase signaling, cell proliferation, and cytoplasmic localization. Specific transcription factor binding motifs were enriched among differentially expressed genes in SFTs with different fusion variants, implicating co-transcription factors in the modification of chimeric NGFI-A binding protein 2 (NAB2)-STAT6-dependent deregulation of EGR1-dependent gene expression. In summary, this study establishes a potential molecular biologic basis for clinicopathologic differences in SFTs with distinct NAB2-STAT6 gene fusion variants.

Survival and Prognostic Analysis after Pulmonary Metastasectomy for Head and Neck Cancer.

BACKGROUND: There is no consensus on the value of pulmonary metastasectomy (PM) for head and neck cancer (HNC). The aim of our single-institution study was to evaluate outcomes and to examine factors influencing 5-year survival of patients undergoing resections for HNC lung metastases. METHODS: All HNC patients undergoing curative-intent PM between January 2008 and December 2018 were retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on patient survival was evaluated using the univariable Cox proportional hazard model. Cutoff values of continuous variables were determined by a receiver operating characteristic analysis. RESULTS: In total, 44 patients (32 males and 12 females, with a median age of 65 years) underwent PM for metastatic HNC. There was one perioperative death, and major complications occurred in 2 (4.5%) patients. The median interval between the treatment of primary tumor and PM was 19.4 months (range: 0-151 months). Median size of the largest resected pulmonary lesion was 1.3 cm (range: 0.3-6.9 cm). Mean follow-up was 21 months (range: 0-123 months), and 5-year overall survival (OS) rate after the first PM was 41%. Resection was complete (R0) in all patients. Larger size of pulmonary metastasis (≥1.4 cm; hazard ratio: 4.49; 95% confidence interval: 1.79-11.27) was a significantly negative prognostic factor. CONCLUSION: Despite the lack of randomized controlled trials, PM for HNC is a reasonable therapeutic option with favorable survival in a selected population. In patients with larger pulmonary lesions, shorter OS after PM is to be expected.

Negative Pressure Wound Therapy Combined With Instillation for Sternoclavicular Joint Infection.

BACKGROUND: There is no consensus on the management of spontaneous sternoclavicular joint infection (SCJI). Negative pressure wound therapy (NPWT) has been widely accepted for SCJI. We reviewed our experience with the management of this condition comparing NPWT alone and NPWT combined with instillation and dwell time. METHODS: We retrospectively analyzed the data of patients with spontaneous SCJI treated in our thoracic unit. RESULTS: From March 2008 to October 2019, 27 patients (21 men and 6 women) underwent NPWT combined with muscle flap transfer after necrosectomy and chest wall resection for SCJI. The median age was 57.1 years (range, 35 to 85). Depending on management, the patients were divided into two groups: 16 patients with NPWT in group 1, and 11 patients with NPWT combined with instillation and dwell time in group 2. The severity of SCJI, extent of chest wall resection, and type of muscle flap were not significantly different (P = .35, P = .858, P = .705, respectively). Median duration of hospital stay and NPWT were shorter in group 2 (30 vs 25 days, and 20 vs 16 days, respectively). The required wound dressing changes were significantly lower in group 2 (P = .008). Statistical trend to higher bacterial eradication in group 2 was noted (P = .093). Postoperative complications including SCJI recurrence, wound seroma, and dehiscence were not significantly different between groups (P = .269). CONCLUSIONS: The NPWT combined with instillation and dwell time appears a useful strategy in patients with SCJI, leading to higher incidence of bacterial eradication and shorter wound care.

Major Pathologic Response after Induction Therapy Has a Long-Term Impact on Survival and Tumor Recurrence in Stage IIIA/B Locally Advanced NSCLC.

BACKGROUND: Major pathologic response (MPR) determines favorable outcome in locally advanced non-small cell lung cancer after induction therapy (IT) followed by lung resection. The aim of this retrospective study was to identify the prognostic relevance of MPR in long-term interval. METHODS: In 55 patients, the survival rate according to MPR and non-MPR was estimated by Kaplan-Meier method and compared using log-rank, Breslow, and Tarone-Ware tests. RESULTS: The IT included chemoradiation with 50.4 Gy (range: 45-56.4 Gy) combined with platinum-based chemotherapy in 52 patients (94.5%) and platinum-based chemotherapy in 3 patients (5.5%). Perioperative morbidity and 30-day mortality were 36 and 3.6%, respectively. The estimated 5-year postoperative and progressive-free survivals were statistically significantly improved in MPR versus non-MPR with 53.5 versus 18% and 49.4 versus 18.5%, respectively. According to the log-rank, Breslow, and Tarone-Ware tests, the MPR demonstrates prognostic significance in early, long-term, and whole postoperative interval. CONCLUSION: MPR is associated with a robust correlation to long-term postoperative and recurrence-free survival improvement, and can potentially simplify the multidisciplinary debate and allow further stratification of adjuvant treatment in multimodality therapy.

Pulmonary metastasectomy for sarcoma-survival and prognostic analysis.

BACKGROUND: Pulmonary metastasectomy (PM) has commonly been performed in patients with controlled metastatic sarcoma. We reviewed our single-institution experience with pulmonary resections for sarcoma to analyse clinical outcome and to identify prognostic factors associated with patient survival. METHODS: All sarcoma patients undergoing curative intent PM between 2008 and 2014 were retrospectively analysed. Factors related to primary tumour, metastases, applied therapy, systematic inflammation and preoperative nutritional condition, associated with survival after PM were evaluated using the univariable Cox proportional hazard model. Cut-off values of continuous variables were determined by a receiver operating characteristic (ROC) analysis. RESULTS: In total, 33 patients (19 male and 14 female, median age 55 years) underwent PM for metastatic sarcoma. There were no perioperative deaths; major complications occurred in 5 (15.2%) patients. The median interval between the treatment of primary tumour and PM was 16 months (range, 0-171 months). The median size of the largest pulmonary lesion was 1.3 cm. Mean follow-up was 37 months (range, 1-100 months) and the 5-year overall survival (OS) rate after first PM was 40.4%. Resection was complete (R0) in 31 (93.9%) patients. In univariable analysis, a shorter interoperative interval [<30 months, hazard ratio (HR) 5.05, 95% confidence interval (CI): 1.15-22.19] and grade 3 (G3) sarcoma (HR 3.52, 95% CI: 1.01-12.25) were significant negative prognosticators. CONCLUSIONS: Despite the lack of randomized controlled trials PM for sarcomatous disease is a reasonable therapeutic option with acceptable survival in a selected patient population. In sarcoma patients with a shorter interoperative interval and G3 tumour, shorter survival after PM can be expected.

Combined recurrent laryngeal nerve monitoring and one-lung ventilation using the EZ-Blocker and an electromyographic endotracheal tube.

BACKGROUND: Intraoperative neuromuscular monitoring (IONM) is a widespread procedure to identify and protect the recurrent laryngeal nerve (RLN) during thyroid surgery. However, for left thoracic surgery with high risk of RLN injury, both reliable recurrent laryngeal nerve monitoring and one-lung ventilation could interfere. METHODS: In this prospective study, a new method for IONM during one-lung ventilation combining RLN monitoring with an electromyographic (EMG) endotracheal tube (ETT) and lung separation using the EZ-Blocker (EZB) is described and its clinical feasibility and effectiveness were assessed. RESULTS: A total of 14 patients undergoing left upper lobe surgery and left upper mediastinal lymph node dissection were enrolled. The EZB was introduced and positioned without any problems and sufficient lung collapse was achieved in all patients. No tracheobronchial injuries or immediate complications occurred. A stable EMG signal was present in all patients and no RLN palsy and no negative side effects of the NIM EMG ETT or the EZB were observed postoperatively. CONCLUSIONS: The described method is technically feasible, easy to apply and save. It provides both reliable IONM and independent lung separation for optimal surgical exposure. The combined use of the EZB and the NIM EMG ETT might reduce the risk for RLN palsy and impaired lung separation during left thoracic surgery with high risk for RLN injury.

Increased expression of the immunosuppressive interleukin-35 in patients with non-small cell lung cancer.

BACKGROUND: The immunosuppressive role of the cytokine IL-35 in patients with non-small cell lung cancer (NSCLC) is poorly understood. In this study, we analysed the localisation and regulation of IL-35 in the lung of patients with non-small cell lung cancer (NSCLC) to further elucidate the immune-escape of cancer cells in perioperative course of disease. METHODS: Interleukin 35 (IL-35) was measured by ELISA in postoperative serum from 7 patients with NSCLC as well as 8 samples from healthy controls. Immunohistochemistry, FACS analysis, real-time PCR, as well as western blot from samples of the control (CTR), peri-tumoural (PT) and the tumoural (TU) region of the lung derived from patients with NSCLC and 10 controls were performed. RESULTS: Here we found elevated levels of IL-35 in the TU region as well as postoperative serum from patients with lung adenocarcinoma. Consistently, we found an increased expression of IL-35+Foxp-3+ cells, which associated with ARG1 mRNA expression and decreased TNFA in the TU region of the lung of patients with NSCLC as compared to their CTR region. Furthermore, in the CTR region of the lung of patients with NSCLC, CD68+ macrophages were induced and correlated with IL-35+ cells. Finally, IL-35 positively correlated with TTF-1+PD-L1+ cells in the TU region of NSCLC patients. CONCLUSIONS: Induced IL-35+Foxp3+ cell numbers in the TU region of the lung of patients with NSCLC associated with ARG1 mRNA expression and with TTF-1+PD-L1+ cells. In the tumour-free CTR area, IL-35 correlated with CD68+ macrophages. Thus inhibitors to IL-35 would probably succeed in combination with antibodies against immune checkpoints like PD-L1 and PD-1 currently used against NSCLC because they would inhibit immunosuppressive macrophages and T regulatory cells while promoting T cell-mediated anti-tumoural immune responses in the microenvironment as well as the TU region of NSCLC patients.

Sternal resection and reconstruction for secondary malignancies.

BACKGROUND: Limited data on sternal and/or anterior chest wall resections for secondary malignancies exist. The purpose of this study was to examine the perioperative outcomes and postoperative overall survival (OS) in patients who underwent sternal and/or anterior chest wall resections for secondary sternal tumors (SSTs). METHODS: A retrospective analysis of all patients who underwent resection of SSTs at single institution between 2000 and 2016 has been performed. OS was estimated using the Kaplan-Meier method. RESULTS: Ten patients underwent sternal and/or anterior chest wall resection for SSTs with curative (70%) or palliative (30%) intent. Two (20%) patients underwent complete and 8 (80%) partial sternal and/or anterior chest wall resection. There were no perioperative deaths, major complications occurred in 3 (30%) patients. Tumor resection was complete (R0) in 5 (50%) patients. The 5-year OS rate was 40%. No OS difference in R0 vs. R1 resections was observed. CONCLUSIONS: Sternal and/or anterior chest wall resections for SSTs can be performed with low morbidity and mortality. Complete SST resection does not assure favorable OS. Sternal resections can be considered palliative treatment option in patients with stable stage IV disease with isolated sternal involvement.