Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis.

Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. Here, we establish that aging of the immune system, regardless of the age of the stroma and tumor, drives lung cancer progression. Hematopoietic aging enhances emergency myelopoiesis, resulting in the local accumulation of myeloid progenitor-like cells in lung tumors. These cells are a major source of IL-1⍺ that drives the enhanced myeloid response. The age-associated decline of DNMT3A enhances IL-1⍺ production, and disrupting IL-1R1 signaling early during tumor development normalized myelopoiesis and slowed the growth of lung, colonic, and pancreatic tumors. In human tumors, we identified an enrichment for IL-1⍺-expressing monocyte-derived macrophages linked to age, poorer survival, and recurrence, unraveling how aging promotes cancer and offering actionable therapeutic strategies.

Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumors.

Monocyte-derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin analysis over the continuum of BM myeloid progenitors, circulating monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing chromatin accessibility and histone mark changes, we show that lung tumors prime accessibility for Nfe2l2 (NRF2) in BM myeloid progenitors as a cytoprotective response to oxidative stress. NRF2 activity is sustained and increased during monocyte differentiation into mo-macs in the lung TME to regulate oxidative stress, in turn promoting metabolic adaptation, resistance to cell death, and contributing to immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs' survival and immunosuppression in the TME, enabling NK and T cell therapeutic antitumor immunity and synergizing with checkpoint blockade strategies. Altogether, our study identifies a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the TME.

[Intra- and perioperative imaging options in neurosurgery]. / Az intra- és perioperatív képalkotás lehetoségei az idegsebészetben.

The treatment of central nervous system tumors is still a major challenge for the oncological and neurosurgical teams. Due to the heterogeneous histological and topological characteristics of these neoplasms, every case requires individual evaluation. In addition to histology and stage, survival is largely determined by the extent of resection, which can be severely limited by the proximity of eloquent brain regions. A key component of current modern neuro-oncological care is the planning and execution of surgical intervention to ensure the longest possible progression-free survival with adequate quality of life. The simultaneous development of several pre- and intra-operative imaging modalities is making optimal therapy more and more accessible and safe. Structural, diffusion and functional MRI offers the possibility to visualize the tumor and the surrounding areas both before and during surgery. For the surgeon, the optimal intra-operative environment, orientation and visual acuity are provided by increasingly sophisticated microscopes, navigation devices, intra-operative imaging equipment, endo- and exoscopes.

The transcriptional control of the VEGFA-VEGFR1 (FLT1) axis in alternatively polarized murine and human macrophages.

Introduction: Macrophages significantly contribute to the regulation of vessel formation under physiological and pathological conditions. Although the angiogenesis-regulating role of alternatively polarized macrophages is quite controversial, a growing number of evidence shows that they can participate in the later phases of angiogenesis, including vessel sprouting and remodeling or regression. However, the epigenetic and transcriptional regulatory mechanisms controlling this angiogenesis-modulating program are not fully understood. Results: Here we show that IL-4 can coordinately regulate the VEGFA-VEGFR1 (FLT1) axis via simultaneously inhibiting the proangiogenic Vegfa and inducing the antiangiogenic Flt1 expression in murine bone marrow-derived macrophages, which leads to the attenuated proangiogenic activity of alternatively polarized macrophages. The IL-4-activated STAT6 and IL-4-STAT6 signaling pathway-induced EGR2 transcription factors play a direct role in the transcriptional regulation of the Vegfa-Flt1 axis. We demonstrated that this phenomenon is not restricted to the murine bone marrow-derived macrophages, but can also be observed in different murine tissue-resident macrophages ex vivo and parasites-elicited macrophages in vivo with minor cell type-specific differences. Furthermore, IL-4 exposure can modulate the hypoxic response of genes in both murine and human macrophages leading to a blunted Vegfa/VEGFA and synergistically induced Flt1/FLT1 expression. Discussion: Our findings establish that the IL-4-activated epigenetic and transcriptional program can determine angiogenesis-regulating properties in alternatively polarized macrophages under normoxic and hypoxic conditions.

Nur77 and PPARγ regulate transcription and polarization in distinct subsets of M2-like reparative macrophages during regenerative inflammation.

Macrophage polarization is a process whereby macrophages develop a specific phenotype and functional response to different pathophysiological stimuli and tissue environments. In general, two main macrophage phenotypes have been identified: inflammatory (M1) and alternatively activated (M2) macrophages characterized specifically by IL-1ß and IL-10 production, respectively. In the cardiotoxin-induced skeletal muscle injury model bone marrow-derived macrophages (BMDMs) play the central role in regulating tissue repair. Bone marrow-derived monocytes arriving at the site of injury differentiate first to M1 BMDMs that clear cell debris and trigger proliferation and differentiation of the muscle stem cells, while during the process of efferocytosis they change their phenotype to M2 to drive resolution of inflammation and tissue repair. The M2 population is formed from at least three distinct subsets: antigen presenting, resolution-related and growth factor producing macrophages, the latest ones expressing the transcription factor PPARγ. Nuclear receptor subfamily 4 group A member 1 (NR4A1; also termed Nur77) transcription factor is expressed as an early response gene, and has been shown to suppress the expression of pro-inflammatory genes during efferocytosis. Here we demonstrate that (1) Nur77 null BMDMs are characterized by elevated expression of PPARγ resulting in enhanced efferocytosis capacity; (2) Nur77 and PPARγ regulate transcription in different subsets of M2 skeletal muscle macrophages during muscle repair; (3) the loss of Nur77 prolongs M1 polarization characterized by increased and prolonged production of IL-1ß by the resolution-related macrophages normally expressing Nur77; whereas, in contrast, (4) it promotes M2 polarization detected via the increased number of IL-10 producing CD206+ macrophages generated from the PPARγ-expressing subset.

Effects of anterior thalamic nucleus DBS on interictal heart rate variability in patients with refractory epilepsy.

OBJECTIVE: Heart rate variability (HRV) changes were investigated by several studies after resective epilepsy surgery/vagus nerve stimulation. We examined anterior thalamic nucleus (ANT)-deep brain stimulation (DBS) effects on HRV parameters. METHODS: We retrospectively analyzed 30 drug-resistant epilepsy patients' medical record data and collected electrocardiographic epochs recorded during video- electroencephalography monitoring sessions while awake and during N1- or N2-stage sleep pre-DBS implantation surgery, post-surgery but pre-stimulation, and after stimulation began. RESULTS: The mean square root of the mean squared differences between successive RR intervals and RR interval standard deviation values differed significantly (p < 0.05) among time-points, showing increased HRV post-surgery. High (0.15-0.4 Hz) and very low frequency (<0.04 Hz) increased, while low frequency (0.04-0.15 Hz) and the LF/HF ratio while awake decreased, suggesting improved autonomic regulation post-surgery. Change of effect size was larger in patients where both activated contacts were located in the ANT than in those where only one or none of the contacts hit the ANT. CONCLUSIONS: In patients with drug-resistant epilepsy, ANT-DBS might positively influence autonomic regulation, as reflected by increased HRV. SIGNIFICANCE: To gain a more comprehensive outcome estimation after DBS implantation, we suggest including HRV measures with seizure count in the post-surgery follow-up protocol.

The epigenetic state of IL-4-polarized macrophages enables inflammatory cistromic expansion and extended synergistic response to TLR ligands.

Prior exposure to microenvironmental signals could fundamentally change the response of macrophages to subsequent stimuli. It is believed that T helper-2 (Th2)-cell-type cytokine interleukin-4 (IL-4) and Toll-like receptor (TLR) ligand-activated transcriptional programs mutually antagonize each other, and no remarkable convergence has been identified between them. In contrast, here, we show that IL-4-polarized macrophages established a hyperinflammatory gene expression program upon lipopolysaccharide (LPS) exposure. This phenomenon, which we termed extended synergy, was supported by IL-4-directed epigenomic remodeling, LPS-activated NF-κB-p65 cistrome expansion, and increased enhancer activity. The EGR2 transcription factor contributed to the extended synergy in a macrophage-subtype-specific manner. Consequently, the previously alternatively polarized macrophages produced increased amounts of immune-modulatory factors both in vitro and in vivo in a murine Th2 cell-type airway inflammation model upon LPS exposure. Our findings establish that IL-4-induced epigenetic reprogramming is responsible for the development of inflammatory hyperresponsiveness to TLR activation and contributes to lung pathologies.

Evidence of islet CADM1-mediated immune cell interactions during human type 1 diabetes.

BACKGROUNDPathophysiology of type 1 diabetes (T1D) is illustrated by pancreatic islet infiltration of inflammatory lymphocytes, including CD8+ T cells; however, the molecular factors mediating their recruitment remain unknown. We hypothesized that single-cell RNA-sequencing (scRNA-Seq) analysis of immune cell populations isolated from islets of NOD mice captured gene expression dynamics providing critical insight into autoimmune diabetes pathogenesis.METHODSPancreatic sections from human donors were investigated, including individuals with T1D, autoantibody-positive (aAb+) individuals, and individuals without diabetes who served as controls. IHC was performed to assess islet hormones and both novel and canonical immune cell markers that were identified from unbiased, state-of-the-art workflows after reanalyzing murine scRNA-Seq data sets.RESULTSComputational workflows identified cell adhesion molecule 1-mediated (Cadm1-mediated) homotypic binding among the most important intercellular interactions among all cell clusters, as well as Cadm1 enrichment in macrophages and DCs from pancreata of NOD mice. Immunostaining of human pancreata revealed an increased number of CADM1+glucagon+ cells adjacent to CD8+ T cells in sections from T1D and aAb+ donors compared with individuals without diabetes. Numbers of CADM1+CD68+ peri-islet myeloid cells adjacent to CD8+ T cells were also increased in pancreatic sections from both T1D and aAb+ donors compared with individuals without diabetes.CONCLUSIONIncreased detection of CADM1+ cells adjacent to CD8+ T cells in pancreatic sections of individuals with T1D and those who were aAb+ validated workflows and indicated CADM1-mediated intercellular contact may facilitate islet infiltration of cytotoxic T lymphocytes and serve as a potential therapeutic target for preventing T1D pathogenesis.FUNDINGThe Johns Hopkins All Children's Foundation Institutional Research Grant Program, the National Natural Science Foundation of China (grant 82071326), and the Deutsche Forschungsgemeinschaft (grants 431549029-SFB1451, EXC2030-390661388, and 411422114-GRK2550).

A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.

Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-ß superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs]).

Transcriptional repression shapes the identity and function of tissue macrophages.

The changing extra- and intracellular microenvironment calls for rapid cell fate decisions that are precisely and primarily regulated at the transcriptional level. The cellular components of the immune system are excellent examples of how cells respond and adapt to different environmental stimuli. Innate immune cells such as macrophages are able to modulate their transcriptional programs and epigenetic regulatory networks through activation and repression of particular genes, allowing them to quickly respond to a rapidly changing environment. Tissue macrophages are essential components of different immune- and nonimmune cell-mediated physiological mechanisms in mammals and are widely used models for investigating transcriptional regulatory mechanisms. Therefore, it is critical to unravel the distinct sets of transcription activators, repressors, and coregulators that play roles in determining tissue macrophage identity and functions during homeostasis, as well as in diseases affecting large human populations, such as metabolic syndromes, immune-deficiencies, and tumor development. In this review, we will focus on transcriptional repressors that play roles in tissue macrophage development and function under physiological conditions.

Changes of the outcomes of epilepsy surgery within 10 years in the National Institute of Clinical Neurosciences, Hungary / Az epilepsziasebészet eredményességének változása 2006 és 2016 között az Országos Klinikai Idegtudományi Intézetben.

Összefoglaló. Bevezetés és célkituzés: A terápiarezisztens fokális epilepsziák sebészeti kezelése elterjedten használt kezelési lehetoség. Célunk az epilepsziasebészet-hatékonyság változásának vizsgálata egy évtizednyi távlatból a budapesti centrumban. Módszerek: Az Országos Klinikai Idegtudományi Intézetben reszektív epilepsziasebészeti beavatkozásokon átesett fokális epilepsziás betegek adatai kerültek feldolgozásra. A vizsgált 10 év beteganyagát két periódusra osztottuk a mutét idopontja szerint (2006-2010 és 2011-2016). Vizsgálati szempontjaink: demográfiai adatok, az epilepszia kezdete és típusa, mágnesesrezonancia-lelet, preoperatív rohamfrekvencia, mutéttípus és szövettani lelet. Az epileptológiai kimenetelt az Engel-klasszifikáció alapján értékeltük. Eredmények: Epilepsziasebészeti beavatkozás 187 betegen történt, akik közül 137-nél került sor reszekciós mutétre. A betegek 65%-ában temporalis, 18%-ában frontalis, míg 7%-ában olyan multilobaris epilepszia igazolódott, mely a temporalis vagy a frontalis lebenyt érintette. Teljes rohammentességet (Engel I/A) az 1. évben 68%-ban, a 2. évben 64%-ban, míg az 5. évben 63%-ban mértünk. A két intervallum összehasonlításakor az 1 éves rohammentesség aránya 60%-ról (temporalis: 67%, extratemporalis: 50%) 73%-ra (temporalis: 79%, extratemporalis: 62%) javult a második periódusban. Az etiológia szempontjából a hippocampalis sclerosis aránya 28%-ról 14%-ra csökkent, a fokális corticalis dysplasiák aránya 22%-ról 31%-ra növekedett. Következtetés: A sebészeti kezelés fokális epilepsziák esetén - alapos elozetes kivizsgálást követoen - általában biztonságos és a legnagyobb arányban sikeres beavatkozás. A legkedvezobb kimenetel temporalis lokalizációban érheto el. A hatékonyság az évek során egyre javuló tendenciát mutatott az egyre nehezebb sebészeti esetek ellenére. Ez magyarázható a sebészeti technikák fejlodésével, illetve a jobb, mutét elotti elektrofiziológiai és képalkotó technikákkal, amelyek bevezetésével pontosabb lokalizáció adható. Orv Hetil. 2021; 162(6): 219-226. INTRODUCTION AND OBJECTIVE: The surgical treatment of medically intractable focal epilepsies is a well established practice. Our aim was to examine the efficacy of epilepsy surgery within a decade long period in our centre in Budapest. METHODS: Data of drug-resistant patients with resective epilepsy surgery in the National Institute of Clinical Neurosciences were evaluated. The examined 10-year period was divided based on the year of the operation in two parts (2006-2010 and 2011-2016). The following data were collected: demography, beginning and type of epilepsy, magnetic resonance, preoperative seizure frequency, type of surgery and histology. Epileptological outcome was based on modified Engel's classification. RESULTS: Out of 187 surgeries, we identified 137 patients with resective intervention: 65% temporal lobe, 18% frontal, and 7% multilobar epilepsy. Seizure-freedom (Engel I/A) was 68% in the first postoperative year, 64% in the second, and 63% in the fifth year. In the first period, 1-year seizure freedom was 60% (temporal: 67% extratemporal: 50%), while in the second period it was 73% (temporal 79%, extratemporal 62%). Hippocampal sclerosis ratio dropped from 28% to 14%, while focal cortical dysplasia ratio increased from 22% to 31%. CONCLUSION: Surgical treatment in focal epilepsy - after thorough presurgical evaluation - is generally safe and successful. The most favorable outcome is in temporal localization. The efficacy tended to improve over time despite of the more challenging cases. This can be explained with the development of surgical techniques and improvement of presurgical localization. Orv Hetil. 2021; 162(6): 219-226.

Unorthodox Transcriptional Mechanisms of Lipid-Sensing Nuclear Receptors in Macrophages: Are We Opening a New Chapter?

Work over the past 30 years has shown that lipid-activated nuclear receptors form a bridge between metabolism and immunity integrating metabolic and inflammatory signaling in innate immune cells. Ligand-induced direct transcriptional activation and protein-protein interaction-based transrepression were identified as the most common mechanisms of liganded-nuclear receptor-mediated transcriptional regulation. However, the integration of different next-generation sequencing-based methodologies including chromatin immunoprecipitation followed by sequencing and global run-on sequencing allowed to investigate the DNA binding and ligand responsiveness of nuclear receptors at the whole-genome level. Surprisingly, these studies have raised the notion that a major portion of lipid-sensing nuclear receptor cistromes are not necessarily responsive to ligand activation. Although the biological role of the ligand insensitive portion of nuclear receptor cistromes is largely unknown, recent findings indicate that they may play roles in the organization of chromatin structure, in the regulation of transcriptional memory, and the epigenomic modification of responsiveness to other microenvironmental signals in macrophages. In this review, we will provide an overview and discuss recent advances of our understanding of lipid-activated nuclear receptor-mediated non-classical or unorthodox actions in macrophages.

The transcription factor EGR2 is the molecular linchpin connecting STAT6 activation to the late, stable epigenomic program of alternative macrophage polarization.

Macrophages polarize into functionally distinct subtypes while responding to microenvironmental cues. The identity of proximal transcription factors (TFs) downstream from the polarization signals are known, but their activity is typically transient, failing to explain the long-term, stable epigenomic programs developed. Here, we mapped the early and late epigenomic changes of interleukin-4 (IL-4)-induced alternative macrophage polarization. We identified the TF, early growth response 2 (EGR2), bridging the early transient and late stable gene expression program of polarization. EGR2 is a direct target of IL-4-activated STAT6, having broad action indispensable for 77% of the induced gene signature of alternative polarization, including its autoregulation and a robust, downstream TF cascade involving PPARG. Mechanistically, EGR2 binding results in chromatin opening and the recruitment of chromatin remodelers and RNA polymerase II. Egr2 induction is evolutionarily conserved during alternative polarization of mouse and human macrophages. In the context of tissue resident macrophages, Egr2 expression is most prominent in the lung of a variety of species. Thus, EGR2 is an example of an essential and evolutionarily conserved broad acting factor, linking transient polarization signals to stable epigenomic and transcriptional changes in macrophages.

The BACH1-HMOX1 Regulatory Axis Is Indispensable for Proper Macrophage Subtype Specification and Skeletal Muscle Regeneration.

The infiltration and subsequent in situ subtype specification of monocytes to effector/inflammatory and repair macrophages is indispensable for tissue repair upon acute sterile injury. However, the chromatin-level mediators and regulatory events controlling this highly dynamic macrophage phenotype switch are not known. In this study, we used a murine acute muscle injury model to assess global chromatin accessibility and gene expression dynamics in infiltrating macrophages during sterile physiological inflammation and tissue regeneration. We identified a heme-binding transcriptional repressor, BACH1, as a novel regulator of this process. Bach1 knockout mice displayed impaired muscle regeneration, altered dynamics of the macrophage phenotype transition, and transcriptional deregulation of key inflammatory and repair-related genes. We also found that BACH1 directly binds to and regulates distal regulatory elements of these genes, suggesting a novel role for BACH1 in controlling a broad spectrum of the repair response genes in macrophages upon injury. Inactivation of heme oxygenase-1 (Hmox1), one of the most stringently deregulated genes in the Bach1 knockout in macrophages, impairs muscle regeneration by changing the dynamics of the macrophage phenotype switch. Collectively, our data suggest the existence of a heme-BACH1--HMOX1 regulatory axis, that controls the phenotype and function of the infiltrating myeloid cells upon tissue damage, shaping the overall tissue repair kinetics.

Connectivity-based segmentation of the brainstem by probabilistic tractography.

Diffusion magnetic resonance imaging is a non-invasive tool increasingly used for the investigation of brain connectivity in vivo. In this paper we propose a method that allows segmentation of the brainstem to four subregions (frontopontine, motor, sensory and reticular) based on connections to supratentorial structures, thereby eliminating the need for using anatomical landmarks within the brainstem for the identification of these subregions. The feasibility of connectivity-based brainstem segmentation was investigated in a group of healthy subjects (n = 20). Multifiber probabilistic tractography was performed using the FMRIB Software Library, and connections between a pontomesencephalic seed mask and four supratentorial target regions (anterior and posterior limbs of the internal capsule, sensory and medial thalamus) were used to determine connectivity maps of the brainstem. Results were compared with a neuroanatomy atlas and histological sections, confirming good anatomic correspondence. The four subregions detected by the connectivity-based segmentation showed good intersubject reproducibility. The presented method may be a potential tool to investigate brainstem connectivity in diseases that distort normal anatomy, and quantitative analyses of the diffusion-related parameters may provide additional information on the involvement of brainstem pathways in certain disease states (e.g., traumatic brain injury, demyelinating disorders, brainstem tumors). The potential clinical applicability of the method is demonstrated in two cases of severe traumatic brain injury.

Inhibition of Amyloid-like Fibril Formation of Trypsin by Red Wines.

The aim of the present study was to examine the potential role and applicability of dietary supplements in reducing the risk of development of amyloid diseases associated with the gastrointestinal tract, such as type II diabetes. Trypsin, a well-known serine protease was used as a model protein in our experiments. The effect of various red wines on the formation of amyloid-like fibrils of trypsin was studied in vitro, in aqueous ethanol, at pH 7.0. Turbidity measurements, aggregation kinetics experiments, Congo red binding assays and electronic circular dichroism spectroscopic measurements were used to follow the aggregation process in the presence or absence of various red wines. The results suggest that red wines effectively inhibit the formation of amyloid-like fibrils of trypsin and the inhibitory effect is dose-dependent. The extent of inhibition was found to be proportional to the total concentration of phenolic compounds.

[The role of D2 lymphadenectomy in the surgical treatment of gastric carcinoma]. / A D2 lymphadenectomia szerepe a gyomorkarcinóma sebészi kezelésében.

The authors examine 145 patients with gastric carcinoma who underwent curative resection with additional D2 lymphadenectomy at the 2nd Surgical Department of DUMHSC between January 1, 1996 and December 31, 2000. Subtotal resection was performed in 103 patients, and total, gastrectomy was performed in 42 patients. Postoperative mortality was 5.5% and disease-related complications occurred in 17.9%. The three-year survival was 49.7%, while in patients with "early" (maximum infiltration to the level of the submucosa) gastric carcinoma 3-year survival rate of was 86.3%. The results correlate with the data in the literature, so the use of D2 lymphadenectomy in the surgical treatment of gastric carcinoma is strongly advised.

[Surgical treatment of pleural metastases in breast cancer]. / Az emlórák pleurametasztázisainak sebészi kezelése.

Pleural metastases of breast cancer is a severe progression of the disease and the treatment is difficult. Distant metastases are mainly treated by chemo-, radio- or hormone therapy, but in recent years surgical intervention is increasingly important. Between the 1st of January 1992 and 31st of December 2001 in the 2nd Department of Surgery University of Debrecen Medical and Health Science Center Medical School of Medicine 43 patients with breast cancer were operated on because of pleural metastases. In these patients biopsy and pleurodesis with talcum insufflation were performed. The surgical treatment was followed by chemotherapy. Pleurodesis was successful at 76.7 percent. The 6, 12 and 24 months survival was 58.1, 39.5 and 16.3 percent. Based on literature data and own experience we conclude that surgical intervention with adjuvant therapy extends life expectancy for patients with pleural metastases. Pleurodesis can prevent or delay hydrothorax, it improves vital functions and the quality of life for patients with pleural metastases.