CD44+ cytokeratin-positive tumor cells in blood and bone marrow are associated with poor prognosis of patients with gastric cancer

Background The phenotypic heterogeneity of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells (DTC) in bone marrow is an important constraint for clinical decision making. Here, we investigated the implications of two different subpopulations of these cells in gastric cancer (GC). Methods GC patients (n=228) who underwent elective gastric resections were prospectively examined for CTC/DTC. The cells obtained from peripheral blood and bone marrow aspirates were sorted by flow cytometry and CD45- cells expressing cytokeratins (8, 18, and 19) and CD44 were identified by immunofluorescent double staining. Results Ninety-three (41%) patients had cytokeratin-positive tumor cells in either blood or bone marrow, while cells expressing CD44 were found in 22 (10%) cases. CK+CD44+ cells were significantly more common among patients with distant metastases (50 vs 19%, P=0.001), while no such correlations were demonstrated for CK+CD44- cells. Detection of CK+CD44+ cells, but not CK+CD44-, was associated with significantly shortened survival. Moreover, the Cox proportional hazards model identified CK+CD44+ cells as a negative prognostic factor with an odds ratio of 2.38 (95% CI 1.28-4.41, P=0.006). Conclusion CD44+ phenotype of cytokeratin-positive cells in blood and bone marrow is an independent prognostic factor in patients with gastric cancer

Preoperative plasma level of IL-10 but not of proinflammatory cytokines is an independent prognostic factor in patients with gastric cancer

There have been many discrepant observations on the serum levels of cytokines in cancer patients and their prognostic value. The purpose of this study was to determine the plasma levels of pro- and anti-inflammatory cytokines and their clinical significance in a large group of patients with gastric carcinoma. The levels of tumour necrosis factor alpha (TNF α), interleukin-12p40 (IL-12p40), IL-12p70, IL-18, IL-10 and soluble TNF receptors I and II sTNF-Rs were investigated in the plasma of 136 consecutive patients with biopsy proven gastric cancer using specific enzymelinked immunoabsorbent assays (ELISA). Survival curves were estimated using the method of Kaplan and Meier and the differences in the survival rates were tested by the logrank test. For multivariate analysis of prognostic factors, the Cox proportional hazard model was used. Proinflammatory cytokines and sTNF-Rs were higher in the whole group of patients in comparison to healthy volunteers. IL-10 was elevated mostly in advanced disease. The increased levels of IL-10 (>10 pg/ml) were associated with significantly poorer survival of patients, while the levels of the other cytokines and sTNF-Rs showed no correlation with prognosis. The increased level of IL-10 is an independent unfavorable prognostic factor in patients with gastric cancer

Hybrid Revascularization for Multivessel Coronary Artery Disease

AbstractObjectivesThe aim of this study was to assess the feasibility of hybrid coronary revascularization (HCR) in patients with multivessel coronary artery disease (MVCAD) referred for standard coronary artery bypass grafting (CABG).BackgroundConventional CABG is still the treatment of choice in patients with MVCAD. However, the limitations of standard CABG and the unsatisfactory long-term patency of saphenous grafts are commonly known.MethodsA total of 200 patients with MVCAD involving the left anterior descending artery (LAD) and a critical (>70%) lesion in at least 1 major epicardial vessel (except the LAD) amenable to both PCI and CABG and referred for conventional surgical revascularization were randomly assigned to undergo HCR or CABG (in a 1:1 ratio). The primary endpoint was the evaluation of the safety of HCR. The feasibility was defined by the percent of patients with a complete HCR procedure and the percent of patients with conversions to standard CABG. The occurrence of major adverse cardiac events such as death, myocardial infarction, stroke, repeated revascularization, and major bleeding within the 12-month period after randomization was also assessed.ResultsMost of the pre-procedural characteristics were similar in the 2 groups. Of the patients in the hybrid group, 93.9% had complete HCR and 6.1% patients were converted to standard CABG. At 12 months, the rates of death (2.0% vs. 2.9 %, p = NS), myocardial infarction (6.1% vs. 3.9%, p = NS), major bleeding (2% vs. 2%, p = NS), and repeat revascularization (2% vs. 0%, p = NS) were similar in the 2 groups. In both groups, no cerebrovascular incidents were observed.ConclusionsHCR is feasible in select patients with MVCAD referred for conventional CABG. (Safety and Efficacy Study of Hybrid Revascularization in Multivessel Coronary Artery Disease [POL-MIDES]; NCT01035567)

Tumour-derived microvesicles contain interleukin-8 and modulate production of chemokines by human monocytes

Background: Tumour-derived microvesicles (TMVs) may interact with cells of the immune system. Our previous observations indicated that TMVs modulate production of cytokines and reactive oxygen species (ROS) by monocytes. This study was designed to determine the role of TMVs in stimulation of chemokine production by human monocytes. Materials and Methods: Chemokines at the mRNA and protein level were detected by real-time PCR and by Western blot, respecively. Chemokine release and chemotaxis of blood leukocytes were analysed by flow cytometry. Matrigel assay was used to determine angiogenesis in a NOD-SCID mice model. Results: TMVs induced secretion of interleukin-8 (CXCL8), monocyte chemoattractant protein-1 (CCL2), macrophage inflammatory protein-1α (CCL3) and MIP-1β (CCL4), and regulated on activation normal T-cells expressed and secreted (CCL5) chemokines and accumulation of their mRNA in monocytes. Moreover, TMVs enhanced angiogenesis in NOD-SCID mice by delivering chemokines and via stimulation of monocytes. In addition, TMVs may be storage for chemokines thus inducing chemotaxis of blood leukocytes. Conclusion: These results further support the role of TMVs in modulation of monocyte biological activity

Long-term survival following surgical ablation for atrial fibrillation concomitant to isolated and combined coronary artery bypass surgery-analysis from the polish national registry of cardiac surgery procedures (KROK)

The current investigation aimed to evaluate long-term survival in patients undergoing isolated and combined coronary artery bypass grafting (CABG) with concomitant surgical ablation for atrial fibrillation (AF). Procedural data from KROK (Polish National Registry of Cardiac Surgery Procedures) were retrospectively collected. Eleven thousand three hundred sixteen patients with baseline AF (72.4% men, mean age 69.6 ± 7.9) undergoing isolated and combined CABG surgery between 2006–2019 in 37 reference centers across Poland and included in the registry were analyzed. The median follow-up was four years (3.7 IQR 1.3–6.8). Over a 12-year study period, there was a significant survival benefit (Hazard Ratio (HR) 0.83; (95% Confidence Interval (CI): 0.73–0.95); p = 0.005) with concomitant ablation as compared to no concomitant ablation. After rigorous propensity matching (LOGIT model, 432 pairs), concomitant surgical ablation was associated with over 25% improved survival in the overall analysis: HR 0.74; (95% CIs: 0.56–0.98); p = 0.036. The benefit of concomitant ablation was maintained in the subgroups, yet the most benefit was appraised in low-risk patients (EuroSCORE < 2, p = 0.003) with the three-vessel disease (p < 0.001) and without other comorbidities. Ablation was further associated with significantly improved survival in patients undergoing CABG with mitral valve surgery (HR 0.62; (95% CIs: 0.52–0.74); p < 0.001) and in patients in whom complete revascularization was not achieved: HR 0.43; (95% CIs: 0.24–0.79); p = 0.006. View Full-Text

Tumour-derived microvesicles (TMV) mimic the effect of tumour cells on monocyte subpopulations

Background: Monocytes/macrophages may be affected by tumour cells via cell-to-cell contact, soluble factors and by tumour-derived microvesicles (TMV). Previous observations indicate that TMV interact with monocytes and alter their immunophenotype and activity. This study was designed to determine interactions of TMV with subpopulations (CD14++CD16– and CD14+CD16++) of human monocytes. Methods: Engulfment of TMV by subsets of monocytes was analysed by flow cytometry. Moreover cytokine release and production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) by CD14++CD16– and CD14+CD16++ cells after TMV stimulation was determined. Results: It was found that TMV are engulfed more efficiently by CD14++CD16– than CD14+CD16++ cells. TMV-activated CD14++CD16– cells produce more ROI and interleukin -10 (IL-10) than CD14++CD16+. CD14+CD16++ cells following TMV stimulation showed an increased release of tumour necrosis factor alpha, IL-12p40 and RNI. Conclusion: TMV significantly modulate biological activity of monocyte subsets with a pattern similar to tumour cells. Therefore, TMV mimic the activating effect of tumour cells on monocytes as assessed by release of cytokines, ROI and RNI

Lung transplantation as a viable option of treatment for pulmonary veno-occlusive disease

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension caused by alteration of pulmonary veins. Many clinical and hemodynamic similarities to idiopathic pulmonary arterial hypertension (IPAH) may cause diagnostic and therapeutic difficulties. This case report is about a patient with PVOD, whose first symptoms of the disease occurred after infectious mononucleosis. Patient was administered with prostacycline (PGI2) mimetic (Treprostinil), what made qualification process and lung transplantation possible. Despite more and more knowledge about causes, ethiopathogenesis and changes in pulmonary veins on molecular level, lung transplantation is the only successful therapeutic option for patients suffering from PVOD