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Circulating tumor cells (CTC) have been studied extensively in various tumor types and are a well-established prognosticator in colorectal cancer (CRC). This is the first study to isolate CTC directly from the tumor outflow in secondary lung tumors. For this purpose in 24 patients with CRC who underwent pulmonary metastasectomy in curative intent blood was drawn intraoperatively from the pulmonary vein (tumor outflow). In 22 samples CTC-enumeration was performed using CellSieve-microfilters and immunohistochemical- and Giemsa-staining. Additionally 10 blood samples were analyzed using the CellSearch-System. We could isolate more CTC in pulmonary venous blood (total 41, range 0–15) than in samples taken from the periphery at the same time (total 6, range 0–5, p = 0.09). Tumor positive lymph nodes correlated with presence of CTC in pulmonary venous blood as in all cases CTC were present (p = 0.006). Our findings suggest a tumor cell release from pulmonary metastases in CRC and a correlation of CTC isolated from the tumor outflow with established negative prognostic markers in metastasized CRC. The presented data warrant further investigations regarding the significance of local tumor compartments when analyzing circulating markers and the possibility of tumor cell shedding from secondary lung tumors.

Lung cancer is the leading cause of cancer-related death and is usually diagnosed at an advanced stage, where lymph node/distant metastases are present. Only in about one-third of patients with non-small cell lung cancer (NSCLC) the disease is diagnosed as localized, for which a complete resection is the treatment of choice and a cure is possible. Hence, in most cases systemic therapy is required, either as part of a multimodal treatment or as sole therapeutic option. Despite advances in individualized approaches and modern chemotherapeutic regimens, the course of the disease remains unfavorable (1-3).It is widely acknowledged that the tumor microenvironment plays a critical role in tumor growth and spread, and in recent years, multiple therapeutic approaches have been developed based on this knowledge (4). In contrast to agents focusing on molecular targets such as the epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK), whose activity is confined to tumors with specific genetic alterations, immunotherapy is effective in various histological subtypes (5-8).Tumor microenvironment consists of tumor cells, the leukocyte infiltrate and the tumor associated immunologic microenvironment. One of the key players, the tumor associated macrophages (TAMs) can make up a large fraction of the tumor mass (9). Depending on the tumor microenvironment, macrophages can be polarized into different functional states, of which the two extremes are known as the M1 and M2 phenotypes. M1 macrophages have been shown to carry out pro-inflammatory, cytotoxic and thus mostly anti-neoplastic effects, whilst the M2 phenotype is responsible for tissue remodeling and repair and is believed to be involved in the subversion of adaptive immunity and thus the immunological interactions that promote tumor growth and progression. TAMs in the tumor microenvironment are mostly found to have the M2 phenotype (10). TAMs secrete a specific pattern of cytokines and chemokines and are one of the main producers of CC-chemokine ligand 18 (CCL18) in this context (11,12). CCL18 is responsible for the recruitment of naive T-cells and dendritic cells, and is capable of inducing regulatory T-cells. In the tumor microenvironment, it has been demonstrated to promote tumor spread and is believed to be one of the factors involved in the immune escape of tumor cells (13)(14)(15)(16)(17). 4667

Background To date, many studies investigated results and prognostic factors of pulmonary metastasectomy (PM) in renal cell cancer (RCC). However, reports concerning repeated resection for patients with recurrent pulmonary metastases (RPM) are limited. In this study, we analyzed safety, efficacy, and prognostic factors for survival after PM focusing on RPM for RCC. Patients and Methods Clinical, operative, and follow-up data of patients who underwent PM or RPM for RCC in our institution were retrospectively collected and correlated with each other from January 2005 to December 2019. Results Altogether 154 oncological pulmonary resections in curative intention as PM or RPM were performed in 82 and 26 patients. Postoperative complications were similar in both groups (n = 22 [26.8%] vs. 4 [15.4%], p = 0.2). Zero mortality was documented up to the 30th postoperative day. RPM was not associated with decreased 5-year-survival compared with PM (66.2 vs. 57,9%, p = 0.5). Patients who underwent RPM for recurrent lung metastases had a better overall survival in comparison with the other treatments including chemotherapy, radiotherapy, immunotherapy, and best supportive care (p = 0.04). In the multivariate analysis, disease-free survival was identified as an independent prognostic factor for survival (hazard ratio: 0.969, 0.941–0.999, p = 0.04). Conclusion RPM is a safe and feasible procedure. The resection of recurrent lung metastases shows to prolong survival in comparison with the other therapeutic options for selected patients with RCC.

Background: Limited information is available about the impact of cardiovascular comorbidities (CVC) on the postoperative course of patients undergoing pulmonary metastasectomy. In this study, we aim to compare the postoperative morbidity, mortality, and the long-term survival of patients with and without CVC undergoing pulmonary metastasectomy (PM).Methods: A retrospective monocentric study was conducted including 760 patients who underwent PM in curative intention. Patients were divided into two groups depending on the presence of CVC. Results:The data from 164 patients with CVC (21.6%) and 596 patients without CVC (78.4%) were investigated. In both groups, zero in-hospital-mortality and limited 30-day mortality was detected.Postoperative complications occurred more often in patients with CVC (N=47, 28.7% vs. N=122, 20.5%, P=0.02). However, most of them were minor (N=37, 22.6% vs. N=93, 15.6%, P=0.03). The presence of multiple CVC (N=18 patients, 40% vs. N=28, 23.9%, P=0.04) and reduced left ventricular function (N=5, 62.5% vs. N=42, 27.1%, P=0.03) were identified as risk factors for postoperative morbidity. Patients with CVC showed reduced overall survival (5-year survival rate: 75.8% vs. 68%, P=0.03). In the multivariate analysis lobectomy [hazard ratio (HR) 0.3, 95% confidence interval (CI): 0.1-0.8, P=0.02] and general vascular comorbidities (HR 2.1, 95% CI: 1.1-3.9, P=0.01) were identified as independent negative prognostic factors.Conclusions: Resection of pulmonary metastases can be performed safely in selected patients with stable CVC. The presence of CVC in patients undergoing PM is associated with reduced overall survival compared to patients without CVC in the long term follow up. However, a prolonged 5-year survival rate of 68% could be achieved.