Patient pathways from first suspicious imaging until final surgical treatment vary and in some instances cause considerable delay. This study aims to investigate the impact of this delay on survival of lung cancer patients. The institutional database was queried to identify patients with primary lung cancer who were treated with primary surgery. Time intervals were defined as date of first suspicious medical images until date of surgical treatment. All patients received PET-CT staging and tissue confirmation prior to treatment planning in a multidisciplinary tumor board. Patients with unknown date of first contact, follow-up CT-scans of pulmonary nodules, or neoadjuvant therapy were excluded. In total, 287 patients treated between 2009 and 2017 were included for further analysis. Median time between first suspicious medical imaging and surgical therapy was 62 (range 23–120) days and did not differ between male and female patients. Patients were then classified into two groups according to the duration of the medical work-up: group A up to 60 days, and group B from 61 to 120 days. Clinical T and N stages were comparable between the groups. There was no difference in overall survival between the two groups. In the subgroup of cT2 tumors (87 patients), there was a significant survival benefit for patients in group A (p = 0.043), while nodal stages, stage migration, lymphatic vessel invasion, grading and other potentially survival-influencing clinical parameters were comparable between the groups. Delay between diagnosis and treatment of lung cancer may result in dismal outcome. Efforts need to focus on improving and streamlining patient pathways to shorten the delay until surgical treatment to a minimum. Process improvement might be achieved by stringent interdisciplinary work-up and a patient-centered approach.

Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as an early marker protein for kidney dysfunction in various clinical settings. In this prospective study we evaluated serial changes of serum and urinary NGAL within the first 7 days after kidney transplantation in 170 consecutive recipients. The main focus of this study was to assess the performance of serum and urinary NGAL in the prediction of delayed graft function (DGF) and two-year graft and patient survival. Serum and urine samples of 170 patients undergoing primary kidney transplantation from October 2010 to December 2012 were prospectively collected from day 0 to 7. NGAL was analyzed by ELISA. Multivariate regression models, receiver-operating characteristics (ROC), and areas under ROC curves (AUC) were used to identify predictors of DGF. DGF occurred in 52 patients (30.6%). Serum (AUC = 0.869) and urinary NGAL (AUC = 0.872) on postoperative day (POD) 2 could accurately predict DGF compared to serum creatinine (AUC = 0.619). Multivariate analyses revealed donor age, serum and urinary NGAL significantly associated with DGF (p<0.001). Recipient age was the only significant factor in a cox regression model influencing two-year graft and patient survival. In conclusion, serum and urinary NGAL are early predictors of DGF after kidney transplantation.

One characteristic of tumor cells is the increased anaerobic metabolism through glycolysis leading to an acidic environment of the tumor. This acidity is linked to tumor progression, invasion and metastasis, besides stimulated survival pathways in the malignant cells. The aim of our analysis is to investigate the role of systemic acid–base parameters such as the pH, bicarbonate, baseexcess and lactate in lung cancer patients. Furthermore, alterations in electrolytes and hemoglobin were investigated regarding their impact on overall survival. Data of 937 non-small-cell lung cancer (NSCLC) patients, who underwent anatomic video-assisted thoracoscopic surgery (VATS) resection, was collected in a prospectively maintained database and analyzed. To minimize confounding effects and due to the retrospective study design, we decided to use data from the first arterial blood gas analysis during surgery and the most recent lab results prior to surgery. We found significant correlations between low systemic bicarbonate (<20 mEq/L) and overall survival (p = 0.006). Hyponatremia (<135 mmol/L) correlated with lower 5-year overall survival (p = 0.004) and decreased disease-free survival (p = 0.017). Hypochloremia (<98 mmol/L) was linked to reduced overall survival (p = 0.003) and hypocalcemia (<1.15 mmol/L) with worse disease-free survival (p = 0.015). Hemoglobin under 12 g/dL for women and 13 g/dL for men was associated with poorer outcomes (p < 0.001). Other acid–base parameters such as the pH (p = 0.563), baseexcess (BE) (p = 0.290) and lactate (p = 0.527) did not show significant differences in overall or disease-free (pH: p = 0.130; BE: p = 0.148; lactate: p = 0.418) survival. Systemic bicarbonate, sodium, calcium, chloride and hemoglobin levels were found as prognostic markers and possible therapeutic targets to improve overall survival. Further investigations are necessary to develop therapeutic strategies.

Background: Cancer immune evasion is critical in non-small cell lung cancer (NSCLC) and has been targeted by immunotherapy. High soluble (s)PD-L1 is associated with reduced survival and treatment failure in advanced stages. Here we evaluated the effects of sPD-L1 on T cells, relapse free survival, and overall survival in early stage NSCLC. Methods: In vitro T cell stimulation was performed in the presence of sPD-L1 to evaluate its immunomodulatory activity. Data from The Cancer Genome Atlas (TCGA) were investigated for PD-L1 splice variants and enzymes involved in proteolytic cleavage (i.e. ADAM10). Plasma from 74 NSCLC (stage IA-IIIB), as well as an additional 73 (control cohort) patients was collected prior to curative surgery. Thereafter sPD-L1 levels from an immunosorbent assay were correlated with patient outcome. Results: In vitro sPD-L1 inhibited IFN-gamma production and proliferation of T cells and induced a terminal effector CD4 T cell subtype expressing CD27. Data from the TCGA demonstrated that elevated mRNA levels of ADAM10 is a negative predictor of outcome in NSCLC patients. To investigate the clinical relevance of these in vitro and TCGA findings, we quantified sPD-L1 in the plasma of early-stage NSCLC patients. In the first cohort we found significantly higher sPD-L1 levels in relapsing NSCLC patients, with a multivariate analysis revealing high sPD-L1 (>1000 pg/mL) as an independent predictor of survival. However, these findings could not be validated in two independent control cohorts. Discussion: Although in vitro and TCGA data support the suppressive effect of sPD-L1 we were unable to translate this in our clinical setting. These results may be due to the small patient number and their heterogeneity as well as the lack of a standardized sPD-L1 ELISA. Our inconclusive results regarding the value of sPD-L1 in early stage NSCLC warrant assay validation and further investigation in larger (neo-)adjuvant trials.

Robotic versus uniportal video-assisted thoracic surgery for lung cancer