Claudia Alexandra Dumitru

Background: Brain metastases (BrMs) represent the most common intracranial tumors, which occur at a significantly higher incidence than primary brain neoplasms. Although some studies addressed the modulation of endothelial cells (ECs) and macrophages in lung and breast BrMs, it is still unclear how these cells are modulated in other BrM types. Methods: Tumor cells (TCs) were isolated from human melanoma, lung and gastrointestinal (GI) BrM tissues, using individual patient isolates (n=2 per tissue origin) as the primary unit of inference. The paracrine effects of BrM-TCs on ECs and macrophages were examined in ex vivo models using BrM-TC-derived supernatants, HUVEC ECs, and peripheral blood monocytes isolated from healthy donors. The functional implications of the macrophages stimulated with BrM-TCs were investigated on autologous T-cells, focusing on T-cell proliferation. Results: None of the BrM-TCs had a direct effect on the ECs regarding MMP release, migration, proliferation and tubulogenesis. Interestingly, lung and GI but not melanoma BrM-TCs polarized macrophages into an M2-like phenotype, characterized by enhanced MMP9 release, increased Arg1 and CD206 expression, as well as elevated IL-6, IL-8, IL-10, and VEGF levels. Moreover, macrophages polarized by lung and GI but not melanoma BrM-TCs inhibited the proliferation of CD8 and CD4 T-cells. Conclusion: These findings indicate that lung and GI but not melanoma BrM-TCs polarize macrophages towards a tumor-promoting, M2-like phenotype. Although the direct effects of BrM-TCs on ECs remain to be further elucidated, our results highlight the need for further comparative studies on BrMs, with particular focus on their histological origins.

Background: Tumor-resident mesenchymal stem/stromal cells (MSCs) were identified in several cancers, and were implicated in regulating multiple aspects of tumor progression. However, the role of tumor-resident MSCs in the pathophysiology of brain metastases (BrMs) -the most prevalent type of malignant brain tumor- is currently unknown, and was investigated in this study. Methods: Tumor-resident MSCs were isolated from fresh human lung-BrM tissues (n=3) and were phenotypically assessed in FFPE lung-BrM tissues (n=11). The paracrine effects of BrM-MSCs on neutrophil granulocytes and endothelial cells (ECs) were examined in ex vivo models using MSC-derived supernatants (SNs), peripheral blood neutrophils from healthy donors and two different EC models (HUVEC and HCAEC). Results: The isolated BrM-MSCs were characterized and validated according to the ISCT ^® criteria. Cells with an MSC-like phenotype were also identified in situ , in the majority of the samples analyzed (9 out of 11). The MSC-derived SNs promoted neutrophil chemotaxis, and prolonged their survival. Additionally, BrM-MSC SNs stimulated neutrophils to release significant levels of pro-angiogenic and pro-invasive matrix metalloprotease (MMP) 9. In contrast, BrM-MSC SNs had no direct stimulatory effect on the ECs regarding MMP2 release, migration and proliferation, and even inhibited the tubulogenesis in HUVEC. However, the latter effect could not be validated with the HCAEC cells. Conclusion: These results indicate that BrMs harbor tumor-resident MSCs that modulate neutrophil biology and function within the BrM microenvironment. While the direct effects of BrM-MSCs on ECs remain to be further characterized, tumor-resident MSCs may play critical roles in the pathophysiology of this disease.

Background/Objectives: Postoperative pneumonia is a common complication in surgical patients. Despite its clinical significance, there is limited evidence regarding its occurrence following intracranial tumor resection, the most common procedure in neurosurgery. The objective of this study is to determine the incidence of postoperative pneumonia, to examine its association with length of hospital stay, and to identify potential risk factors. Methods: A retrospective cohort study was conducted on 1481 patients who underwent intracranial tumor resection in our department over a ten-year period, excluding the influence of anticoagulant or antiplatelet medications. Results: Of the 1481 patients included in this study, postoperative pneumonia occurred in 1.48% of cases. Smoking status (p = 0.014) and prolonged hospital stay (p = 0.011) emerged as significant risk factors in the univariate analysis for postoperative pneumonia in patients undergoing brain tumor resection. In contrast, demographic factors (age, sex, body mass index), pre-existing comorbidities (hypertension, diabetes, cardiovascular disease, chronic inflammatory conditions), and laboratory parameters did not show significant associations with the development of postoperative pulmonary infection. Conclusions: This study identified pre- and postoperative risk factors associated with pneumonia following craniotomy for intracranial tumors. These findings may provide a valuable framework for pre- und postoperative risk assessment and guide strategies to mitigate the occurrence of postoperative pneumonia.

Background/Objectives: Postoperative intracerebral hematomas (POHs) are a common complication following brain tumor surgery and are typically associated with unfavorable outcomes. While extensive hemorrhages have been studied extensively, smaller, Non-Space-Occupying hemorrhages are frequently detected, yet their clinical relevance and associated risk factors remain insufficiently understood. This study aimed to identify predictive factors for the occurrence of Non-Space-Occupying postoperative cerebral hemorrhages in patients undergoing brain tumor resection. Methods: A total of 1481 patients without a history of anticoagulant or antiplatelet therapy underwent brain tumor surgery at our neurosurgical institute over a ten-year period. Non-Space-Occupying postoperative hemorrhages were diagnosed in 84 patients using cranial computed tomography (cCT) or magnetic resonance imaging (cMRI) performed after the tumor resection. Demographic data, pre-existing comorbidities, and tumor characteristics were collected and analyzed. Results: Non-Space-Occupying POHs occurred in 5.6% of patients. The most frequent tumor type associated with POHs was glioblastoma multiforme (N = 33; 39.3%), followed by metastatic lesions (N = 9; 10.7%) and benign primary intracranial neoplasms (N = 31; 38%). None of the affected patients exhibited new neurological deficits or signs of increased intracranial pressure. A multivariate analysis identified the tumor size as an independent risk factor for Non-Space-Occupying POHs (p = 0.002), with patient age emerging as the strongest predictor (p = 0.001). Conclusions: Non-Space-Occupying POHs after a brain tumor resection are significantly associated with the tumor size, an advanced patient age, and the presence of pre-existing liver disease. The recognition of these risk factors may facilitate targeted perioperative monitoring and guide postoperative management strategies.

Background: p120-catenin, COL4A2 and SOX10 are emerging as modulators of glioma pathophysiology and progression. This study aimed to characterize the expression pattern of these markers in glioma tissues with different degrees of malignancy, and tested their prognostic value for the outcome of glioblastoma IDH wild-type (GBM IDH ^wt ) patients, with an additional focus on potential sex-related differences. Methods: All markers were assessed by immunohistochemistry in tissue microarrays prepared from healthy brain (n=38), astrocytoma grade 2 (n=24), astrocytoma grade 3 (n=22), and GBM IDH ^wt (n=204) samples. Correlation analyses were performed using Spearman’s Rho, and survival analyses (5-year overall survival and 1-year progression-free survival) were performed using Kaplan-Meier curves, log-rank test and multivariate proportional hazard models. Results: The levels of p120-catenin significantly increased with the degree of glioma malignancy (pwt patients (HR = 1.861, CI = 1.303-2.658, pwt patients (HR = 1.552, CI = 1.025-2.352, p=0.038). Interestingly, SOX10 was an independent prognostic factor only in female patients (HR = 2.842, CI = 1.241-6.511, p=0.014). Regarding progression-free survival, p120-catenin was a significant prognostic factor in the whole cohort of GBM IDH ^wt patients (HR = 2.542; CI = 1.499-4.312; p<0.001) and in the male patients (HR = 2.431; CI = 1.222-4.836; p=0.011), while SOX10 did not predict the progression-free survival in any group of patients. For COL4A2, we found no significant associations with the patients’ outcome, irrespective of sex. Conclusions: p120-catenin is a potential tumor-promoting factor in glioma, and a prognostic marker in GBM. In contrast, COL4A2 and SOX10 appear to act as tumor suppressors in glioma pathophysiology. SOX10 may additionally be a valuable prognostic marker in female GBM patients.

Background/Objectives: This study aimed to identify risk factors for postoperative wound infections and healing disorders in patients with brain tumors, based on a large, single-center analysis, and to establish an evidence-based foundation for prevention. Methods: A retrospective analysis was conducted on 1480 patients who underwent intracranial tumor resection in our department over a ten-year period, without the influence of anticoagulant or antiplatelet medication. Potential predictors of wound healing disorders were evaluated, focusing on demographic variables and pre-existing conditions. Results: Among the 1480 patients, postoperative wound infections occurred in 47 cases, corresponding to a cumulative incidence of 3.17%. Platelet count (p = 0.018) and partial thromboplastin time (p = 0.011) emerged as potential risk factors for postoperative wound infections. Length of hospital stay appeared as a distinct outcome-associated marker in cases of postoperative wound infection (p = 0.018). In contrast, demographic characteristics (age, sex, blood type), comorbidities (hypertension, diabetes mellitus, cardiovascular disease, kidney disease, chronic inflammatory conditions), and other surgical or laboratory parameters showed no significant association with wound healing disorders. Conclusions: In patients with brain tumors undergoing surgery without the influence of anticoagulant or antiplatelet therapy, most demographic factors, common comorbidities, and selected laboratory parameters were not associated with an increased risk of postoperative wound infections. Awareness of the identified risk factors may help guide preventive strategies and nursing care.

Postoperative hemorrhage (POH) is a rare but serious complication of cranial neurosurgery, often resulting in neurological deterioration and necessitating urgent surgical intervention. Despite its clinical relevance, POH remains underreported and insufficiently understood. This study aimed to identify potential risk factors including perioperative variables and tumor-related characteristics associated with POH requiring surgical evacuation. A total of 1862 cranial tumor procedures were performed in our department over a 10-year period. Data on perioperative parameters and tumor characteristics were retrospectively collected and analyzed. Statistical analyses were conducted to assess associations of them to POH. Statistical analysis revealed several peri- and postoperative variables significantly associated with POH in univariate analyses. These included intraoperative blood loss (p = 0.012) and length of postoperative hospital stay (p = 0.016). Furthermore, the outcomes measured using the Glasgow Outcome Scale (p < 0.001) and the Karnofsky Performance Scale (p < 0.001) showed also statistical relevance as a result of postoperative bleeding in these patients. The findings suggest that specific perioperative factors particularly intraoperative blood loss are associated with an increased risk of POH after intracranial tumor surgery. Additionally, prolonged hospitalization and worsened functional outcomes were linked to the occurrence of postoperative hemorrhage. In contrast, tumor-specific characteristics and routine laboratory values showed no significant association with hemorrhagic complications in this cohort.

Background: Postoperative hemorrhage (POH) is a rare yet serious complication of cranial surgery, potentially resulting in extended hospitalization, neurological impairment, or death. Existing predictive models often encompass diverse cranial pathologies, despite differing mechanisms of POH depending on the underlying condition. There is a lack of large-scale investigations focusing exclusively on POH following surgery for intracranial tumors. This study aimed to assess demographic variables—age, sex, and blood type—and pre-existing medical conditions as potential risk factors for POH in this specific context. Methods: A retrospective review was conducted on medical records of 1862 adult patients who underwent primary surgical resection of intracranial tumors. Univariate and multivariate analyses were applied to identify associations between POH and demographic or clinical characteristics. Results: POH, defined as postoperative hematoma necessitating surgical evacuation, was observed in 31 patients (1.7%). Univariate analysis revealed no statistically significant correlation between POH and demographic factors (age, sex) or pre-existing conditions such as hypertension, diabetes mellitus, cardiac disease, or liver dysfunction. Conclusions: The study found no evidence that demographic variables or pre-existing medical conditions independently contribute to the risk of POH following intracranial tumor resection in adults.