scholarly journals The effect of chemotherapy on endothelial function and microcirculation in patients with gastric cancer

Kardiologiia ◽  
2020 ◽  
Vol 60 (2) ◽  
pp. 89-95
Author(s):  
Yu. Yu. Kirichenko ◽  
I. S. Ilgisonis ◽  
Yu. N. Belenkov ◽  
E. V. Privalova ◽  
Yu. I. Naymann ◽  
...  

Objective. To evaluate and study the dynamics of endothelial dysfunction instrumental indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer (adenocarcinoma) before and after chemotherapy; compare it with the results obtained from healthy volunteers and patients with cardio-vascular diseases.Materials and Methods. The study included 65 people: 25 healthy volunteers, 15 patients with known cardio-vascular diseases (CVD) and 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage 2—4 who underwent surgical treatment followed by chemotherapy according to the FOLFOX, XELOX, and XP regimes. For non-invasive assessment of the vascular wall’s state of large vessels and microcirculation, all patients in the main group underwent computer nailfold capillaroscopy and finger photoplethysmography before chemotherapy and within a month after the completion of the last course. For healthy volunteers and patients with CVD, the above studies were performed once during the examination.Results. The data obtained indicate a significant increase in the reflection index of small muscle arteries (RI) and the stiffness index of large conducting arteries (aSI) during chemotherapy. In cancer patients, even before the treatment, endothelial dysfunction was detected, which significantly worsened after treatment (occlusion index (IO) before and after chemotherapy 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p<0.0002, respectively). Significant differences in the compared indices in cancer patients and CVD group were revealed only after chemotherapy. Significant structural and functional disorders of capillaries were noted in the studied groups, which also worsened during chemotherapy in the main group (density of the capillary network at rest 43.23cap/mm2 vs. 42.19cap/mm2, p <0.01, respectively; density of the capillary network after the reactive hyperemia test 46.77cap/mm2 vs. 44.11cap/mm2, p<0,02, respectively).Conclusion. In this study, for the first time, the dynamics of endothelial dysfunction indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer were studied, and a reliable increasing of these changes was proved during chemotherapy. The results indicate the need for a further search for accurate and effective methods of identifying early signs of close and distant vasculotoxicity, the development of individual prevention programs in order to significantly reduce the risk of cardiovascular events during and after chemotherapy.

2021 ◽  
Vol 20 (Supplement_1) ◽  
Author(s):  
A Emelianov ◽  
YU Kirichenko ◽  
I Ilgisonis ◽  
YU Belenkov ◽  
E Privalova ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The reported study was funded by Russian Foundation for Basic Research (RFBR) project number 19-315-90034 Background. Nowadays gastric cancer is one of the leading causes of world cancer mortality. Modern chemotherapy (CT) significantly improves survival and quality of life among these patients. Unfortunately, anticancer drugs induce some biomolecular disorders, which influence endothelial dysfunction and microcirculation lesions, subsequently leading to vasculo- and cardiotoxicity. The aim To study the dynamics of endothelial dysfunction’s (ED) biomarkers (endothelin-1 (ET-1), von Willebrand factor (VWF)) in patients with gastric cancer before and after CT. Material and methods The study included 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage II - IV, who have been treated by CT including platinum compound (oxaliplatin, cisplatin) and fluoropyrimidine group (5-fluorouracil, capecitabine) and are proven to be cardiovasculotoxic. All patients underwent blood tests, computer nailfold capillaroscopy and finger photoplethysmography (non-invasive assessment of vascular wall stiffness and endothelial function), electrocardiography (ECG), 24-hour ECG, echocardiography before CT and within a month after the last course. Results The median patients’ age was 64 ± 13 years; 68% were male; 52% had a prior cardiac illness: arterial hypertension (n = 12, 48%), coronary artery disease (n = 7, 28%), chronic heart failure (n = 3, 12%). The data obtained showed that ET-1 median levels were below normal values and did not change during CT: 0,95pg/ml (0,6;1,4) vs. 0,94pg/ml (0,7;1,4), р&lt;0,9 (N = 1–3pg/ml), before and after CT respectively. The level of VWF remained within normal ranges and did not significantly differ in cancer patients before and after treatment 0,75IU/ml (0,7;0,9) vs. 0,8IU/ml (0,74;0,9), р&lt;0,6 (N = 0,5–1,5IU/ml). Even before CT, endothelial dysfunction was detected, which significantly worsened after the treatment (occlusion index (IO) before and after CT 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p &lt; 0.0002, respectively). During data analysis, significant correlations were found: between ET-1 level and IO (r = 0.554, p = 0,006), ET-1 and percentage of capillary recovery (r= -0.7, p = 0,029) [both parameters characterize functional abnormalities of the microvasculature], ET-1 and the quantity of supraventricular extrasystoles (r=-0.48, p = 0,032). Conclusion In this study, the dynamics of ED biomarkers in patients with gastric cancer were studied. Even though reliable changes were not proven for the assessed molecular parameters ET-1 and VWF during CT (supposing depletion of endothelin system, small patient cohort), the above parameters may be used for identifying early signs of close and long-term cardio/vasculotoxicity due to significant positive correlations with microvasculature lesions. Further bigger trials for identification of other accurate and effective laboratory methods of detecting early features of vasculotoxicity are required.


2021 ◽  
Vol 20 (7) ◽  
pp. 2923
Author(s):  
Yu. Yu. Kirichenko ◽  
I. S. Ilgisonis ◽  
T. V. Ivanova ◽  
A. S. Zolotukhina ◽  
N. V. Khabarova ◽  
...  

Aim. To study the effect of multiagent chemotherapy on structural and functional vascular, electrophysiological parameters and cardiac hemodynamics in patients with stomach cancer.Material and methods. The study included 3 groups of 25 people: healthy volunteers, those with established cardiac disease (hypertension + coronary artery disease), gastric adenocarcinoma (fluoropyrimidine/platinum-based chemotherapy). Cancer patients before and after chemotherapy courses underwent non-invasive assessment of vascular wall and endothelial dysfunction (videocapillaroscopy, digital photoplethysmography), as well as electrocardiography and echocardiography. Healthy volunteers and cardiac patients were examined once.Results. In cancer patients, even before chemotherapy courses, endothelial dysfunction (ED) (occlusal index, 1,7 (1,4; 1,9), normal values >1,8) and structural vascular disorders (stiffness index, 8,9 m/s (7,7; 9,7), normal values <8 m/s; refractive index, 32,4% (27,5; 37,7), normal values <30%). All above-mentioned parameters significantly worsened after multiagent chemotherapy (progression of ED and vascular wall remodeling: occlusal index, 1,3 (1,2; 1,5) (p<0,0002); stiffness index, 10,3 m/s (9,5; 11,2) (p<0,0001); reflection index, 40,2% (35,5; 43,6) (p<0,001) Decrease in left ventricular ejection fraction and diastolic function was detected. The number of supraventricular and ventricular premature beats during chemotherapy increased 9 and 10 times, respectively (p<0,05).Conclusion. The study for the first time assessed the effect of multiagent chemotherapy on ED, vascular stiffness and cardiac hemodynamics in patients with gastric cancer. A significant aggravation of all endothelial function parameters after treatment has been proven, which requires further study in order to develop criteria for early cardiovascular toxicity. 


Kardiologiia ◽  
2020 ◽  
Vol 60 (5) ◽  
pp. 35-40
Author(s):  
Yu. Yu. Kirichenko ◽  
Yu. N. Belenkov ◽  
E. V. Privalova ◽  
Yu. I. Naymann ◽  
E. P. Gitel ◽  
...  

Aim To evaluate dynamics of biomarkers for endothelial dysfunction (ED), including endothelin-1 (ET-1) and von Willebrand factor (VWF) in patients with stomach cancer (adenocarcinoma) before and after polychemotherapy (PCT); to compare these results with respective values in healthy volunteers and patients with cardiovascular diseases (CVD); to study correlations of the ED biomarkers with indexes of instrumental evaluation of endothelial dysfunction.Material and methods The study included 75 participants, including 25 healthy volunteers (control group), 25 patients with documented CVDs (arterial hypertension + ischemic heart disease), and 25 patients of the main group with histologically documented stage II-IV stomach cancer (adenocarcinoma) who received different courses of PCT with platinum-based agents (oxaliplatin, cisplatin) and fluoropyrimidines (5 fluorouracil, capecitabin). Laboratory measurement of ED biomarkers, computerized nailfold video capillaroscopy (CNVC), and finger laser photoplethysmography (PPG) (methods for noninvasive evaluation of vascular wall and ED), electrocardiography, 24-h ECG Holter monitoring, and echocardiography (EchoCG) were performed for all patients of the main group prior to PCT and within one months after the last course completion. This evaluation was performed once for healthy volunteers and patients of the CVD group upon inclusion into the study.Results In the main group, ET-1 levels were non-significantly lower than normal and did not change during the courses of antitumor treatment (0.95 [0.6; 1.4] and 0.94 [0.7; 1.4] pg /ml (р<0.9) before and after PCT, respectively). Statistically significant differences were found between the control group and oncological patients after the treatment (р<0.04). Levels of VWF remained within the normal range in all examined participants and did not significantly differ between study groups, including oncological patients before and after the specific treatment (р>0.05 for all comparisons). The correlation analysis detected significant correlations of ET-1 levels with functional disorders of microcirculation, ET-1 with the occlusion index (rs=0.56; p=0.005), ЕТ-1 with percentage of capillary restoration (PCR, rs= –0.72; p=0.018) and with the incidence rate of supraventricular extrasystole (rs=0.48; p=0.032).Conclusion The dynamics of ED biomarkers was studied for the first time in patients with stomach cancer receiving a specific antitumor therapy. Although no significant changes in ЕТ-1 and VWF were observed during the PCT (probably due to exhaustion of the endothelial system and a small patient sample), these indexes can be considered as early vasculotoxicity markers due to the presence of significant correlations with indexes of impaired endothelial function according to the results of instrumental evaluation.


2019 ◽  
Vol 156 (6) ◽  
pp. S-1027
Author(s):  
Yo Han Kim ◽  
Yong Eun Park ◽  
Yumun Jeong ◽  
Tae Young Park ◽  
Su Jin Jeong ◽  
...  

2021 ◽  
Vol 22 (24) ◽  
pp. 13288
Author(s):  
Svitlana Demyanets ◽  
Stefan Stojkovic ◽  
Kurt Huber ◽  
Johann Wojta

In this review, we focus on the actual understanding of the role of IL-33 in vascular biology in the context of the historical development since the description of IL-33 as a member of IL-1 superfamily and the ligand for ST2 receptor in 2005. We summarize recent data on the biology, structure and signaling of this dual-function factor with both nuclear and extracellular cytokine properties. We describe cellular sources of IL-33, particularly within vascular wall, changes in its expression in different cardio-vascular conditions and mechanisms of IL-33 release. Additionally, we summarize the regulators of IL-33 expression as well as the effects of IL-33 itself in cells of the vasculature and in monocytes/macrophages in vitro combined with the consequences of IL-33 modulation in models of vascular diseases in vivo. Described in murine atherosclerosis models as well as in macrophages as an atheroprotective cytokine, extracellular IL-33 induces proinflammatory, prothrombotic and proangiogenic activation of human endothelial cells, which are processes known to be involved in the development and progression of atherosclerosis. We, therefore, discuss that IL-33 can possess both protective and harmful effects in experimental models of vascular pathologies depending on experimental conditions, type and dose of administration or method of modulation.


2021 ◽  
Vol 27 (3) ◽  
pp. 24-29
Author(s):  
Zheyna Cherneva ◽  
Radostina Cherneva

COVID-19 infection is characterized with hyperstimulated infl ammatory response that affects lungs, cytokine storm and acute respiratory distress syndrome. Thrombotic complications are the leading reason for death in COVID-19 patients. Those of them with previous cardio-vascular diseases or risk factors – obesity, arterial hypertension, diabetes mellitus, advanced age are with higher risk for worse clinical outcome. Coagulopathy as well as thrombocytopathy and endothelial dysfunction are signifi cant pathophysiological factors for the severe clinical course of the infection. Beside anticoagulation therapy, targetеd strategies regarding thrombocytopathy and endothelial dysfunction are necessary for the treatment of patients with COVID-19 infection. 


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16026-e16026
Author(s):  
Si Tao ◽  
Xin Liu ◽  
Chunhui Jin ◽  
Rongrong Chen

e16026 Background: Peritoneum is a common site of recurrence and metastasis of gastric cancer. The traditional clinical methods have poor sensitivity for the diagnosis of peritoneal metastasis, and there is no effective marker for predicting peritoneal metastasis of gastric cancer. In this study, the genetic profiles of primary tumors in gastric cancer patients with and without peritoneal metastasis, as well as the genetic alterations before and after metastasis in the same patient were analyzed to explore the genetic alterations associated with peritoneal metastasis. Methods: 232 patients with stage Ⅳ gastric cancer were divided into PM group and non-PM group according to whether there was peritoneal metastasis, DNA based Next Generation Sequencing (NGS) with a 1021 gene panel was performed on their samples. Clinical information was obtained synchronously from physicians and surgeons. Results: There was no significant difference in baseline clinical characteristics between patients in PM and non-PM groups. Molecular analysis revealed that in the PM group, the incidence of CDH1, CDH23, HDAC1, IDH1, KRAS, MED12, RHOA, NOTCH2, TGFBR1 mutations was significantly higher in PM group than that in non-PM group, and these mutated genes were mostly located in wnt/β- catenin and MAPK signaling pathway. On the contrary, the incidence of ERBB2 and CCNE1 amplification was significantly higher in non-PM group than in the other group. Further analysis of samples before and after peritoneal metastasis of 13 patients did not find significant differences in genetic alterations. Conclusions: Compared with other sites, the primary tumor of gastric cancer patients with peritoneal metastasis seems to have its unique molecular characteristics, and large-panel NGS can help us identify this part of patients. Future research may need to clarify whether more radical treatment strategies are needed for these patients.


2018 ◽  
Vol 17 (4) ◽  
pp. 652-660
Author(s):  
SP Mittal ◽  
Harendra Singh Sandhu ◽  
Bant Singh

Introduction: Apart from classical functions, vitamin D has autocrine function. Autocrine function of vitamin D has a potential impact on the morbidity and mortality in the Chronic Kidney Disease patients. This study is undertaken to observe probable modality, if present, between post Hemodialysis (HD) decrease in vitamin D levels and clinical deterioration in CKD patients.Method & Material: 63 patients (32 males and 31 females) of Stage – 5 CKD were studied. There vitamin D was estimated before and after HD on first and subsequent maintenance HDs all patients with or without comorbidities.Results: Pre HD total vitamin D levels were ‘deficient’ (58.73%) and ‘sufficient’ in 38.1%, almost equal in patients of both sexes despite intake of supplement containing Calcium and Calcitriol. Post HD vitamin D levels were detected to be markedly low, seems to be ‘washed out’ during HD, in 85.71% of patients (29 males and 27). Vitamin D ‘wash out’ effect was also observed in subsequent maintenance HDs. Females and elderly patients were more prone to vitamin D ‘wash out’. Conventional therapy with vitamin D supplements can replenish but could not prevent its post HD ‘wash out’.Conclusion: It seems, in CKD the deleterious effects of post HD vitamin D deficiency are due to appreciable autocrine dysfunctions resulting in cardio vascular diseases (CVDs) and comorbidities especially diabetes mellitus add to worsening of CVDs, which are the main causes of high morbidity and mortality in these patients.Bangladesh Journal of Medical Science Vol.17(4) 2018 p.652-660


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