Search Results (25)

Background: Postoperative delirium (POD) is a neurocognitive syndrome affecting patients undergoing surgery. It is a frequent complication of coronary artery bypass grafting (CABG) and is associated with higher morbidity, mortality and treatment costs. This study aimed to investigate the relationship between gaseous microemboli (GME) load during cardiopulmonary bypass (CPB) and subsequent POD in patients undergoing CABG. Methods: In total, 102 patients undergoing elective on-pump CABG were evaluated in this observational study. An ultrasonic microbubble counter, with probes placed on the arterial and venous lines, was used during CPB to evaluate the GME load for each patient. During the first postoperative week, the patients were examined for the presence of POD. Results: Patients diagnosed with POD had higher number of bubbles in the arterial CPB line (5382.8 (4127.8–6637.8) vs. 2389.4 (2033.9–2745.0), p < 0.001), higher volume of bubbles in both the venous (24.2 µL (16.8–31.6) vs. 12.4 µL (9.7–15.1), p = 0.004) and arterial lines (1.82 µL (1.43–2.21) vs. 0.29 µL (0.22–0.36), p < 0.001), lower quality factor (QF) values (p = 0.039), a lower venoarterial reduction in bubble number (83.0% (77.8–88.1) vs. 92.4% (90.9–93.8), p = 0.001) and a lower venoarterial reduction in bubble volume (88.8% (85.4–92.2) vs. 96.3% (95.2–97.3), p < 0.001) compared to the patients without POD. Older age (p = 0.005), a lower reduction in bubble volume (p < 0.001) and lower QF values (p = 0.004) were significant independent predictors of POD. Conclusions: Our findings indicate a strong association between GME and the occurrence of POD, which entails that all available actions should be implemented to prevent their generation and facilitate the elimination of GME from the CPB circuit. Full article

Background and Clinical Significance: Carotid stump syndrome (CSS) is a rare and unexpected cause of recurrent ischemic ipsilateral events in the carotid vascular territory despite the demonstrated occlusion of the internal carotid artery (ICA). It is believed to be caused by microemboli due to turbulent blood flow in the patent stump of the occluded ICA that passes through anastomotic channels and retrograde flow into the middle cerebral artery circulation. Case Presentation: We describe the case of a 65-year-old male patient who suffered multiple concurrent transient ischemic attacks (TIAs) with a totally occluded ipsilateral ICA revealed by computed tomography angiography (CTA). He was diagnosed with CSS, which required the safest therapeutic approach. A further investigation with digital subtraction angiography (DSA) was performed, and a trickle of blood flow was observed in the reportedly occluded ICA. The diagnosis of a true ICA occlusion was withdrawn, and a diagnosis of pseudo-occlusion was established, affecting the final treatment strategy. Therefore, the patient underwent an ipsilateral carotid endarterectomy (CEA), and he has remained asymptomatic since then. Conclusions: The differentiation between a pseudo-occlusion and a true ICA occlusion is essential in promptly managing acute recurrent ipsilateral ischemic strokes in the carotid vascular territory. A further investigation with DSA in cases with a totally occluded ICA using CTA is essential for excluding pseudo-occlusions in ipsilaterally symptomatic patients. Full article

Background: Most breast cancer-related deaths are caused by distant metastases and drug resistance. It is important to find appropriate biomarkers to monitor the disease and to predict patient responses after treatment early and accurately. Many studies have found that clustered circulating tumor cells, with more correlations with metastatic cancer and poor survival of patients than individual ones, are promising biomarkers. Methods: Eighty samples from eleven patients with breast cancer during follow-up visits were examined. By using a microfluidic chip and imaging system, the number of circulating tumor cells and microemboli (CTC/CTM) were counted to assess the distribution in stratified patients and the potential in predicting the disease condition of patients after treatments during follow-up visits. Specific components and subtypes of CTM were also preliminarily investigated. Results: Compared to CTC, CTM displayed a distinguishable distribution in stratified patients, having a better AUC value, in predicting the disease progression of breast cancer patients during follow-up visits in this study. Four subtypes were categorized from the identified CTM by considering different components. In combination with CEA and CA153, enumerated CTC and CTM from individual patients were applied to monitor the disease condition and patient response to the therapy during follow-up visits. Conclusions: The CTM and its subtypes are promising biomarkers and valuable tools for studying cancer metastasis and longitudinally monitoring cancer patients during follow-up visits. Full article

Circulating tumor cells (CTCs) and/or circulating tumor microemboli (CTM) from non-small cell lung cancer (NSCLC) patients may be a non-invasive tool for prognosis, acting as liquid biopsy. CTCs interact with platelets through the transforming growth factor-β/transforming growth factor-β receptor type 1 (TGF-β/TGFβRI) forming clusters. CTCs also may express the Cluster of Differentiation 47 (CD47) protein, responsible for the inhibition of phagocytosis, the “don’t eat me” signal to macrophages. Objectives: To isolate, quantify and analyze CTCs/CTMs from metastatic NSCLC patients, identify TGFβRI/CD47 expression in CTCs/CTMs, and correlate with progression-free survival (PFS). Methods: Blood (10 mL) was collected at two time-points: T1 (before the beginning of any line of treatment; T2 (60 days after initial collection). CTCs were isolated using ISET^®. Immunocytochemistry was conducted to evaluate TGFβRI/CD47 expression. Results: 45 patients were evaluated. CTCs were observed in 82.2% of patients at T1 (median: 1 CTC/mL; range: 0.33–11.33 CTCs/mL) and 94.5% at T2 (median: 1.33 CTC/mL; 0.33–9.67). CTMs were observed in 24.5% of patients and significantly associated with poor PFS (10 months vs. 17 months for those without clusters; p = 0.05) and disease progression (p = 0.017). CTMs CD47+ resulted in poor PFS (p = 0.041). TGFβRI expression in CTCs/CTMs was not associated with PFS. Conclusion: In this study, we observed that CTC/CTM from NSCLC patients express the immune evasion markers TGFβRI/CD47. The presence of CTMs CD47+ is associated with poor PFS. This was the first study to investigate CD47 expression in CTCs/CTM of patients with NSCLC and its association with poor PFS. Full article

Importance: The extent to which surgical management of oral squamous cell carcinoma (OSCC) disseminates cancer is currently unknown. Objective: To determine changes in numbers of malignant cells released into systemic circulation immediately following tumour removal and over the first seven post-operative days. Design: An observational study from March 2019 to February 2021. Setting: This study was undertaken at Queen Mary University Hospital, Hong Kong. Participants: Patients with biopsy-proven oral SCC were considered for eligibility. Patients under 18 years of age, pregnant or lactating women and those unable to understand the study details or unable to sign the consent form were excluded. Twenty-two patients were enrolled (12 male and 10 female) with mean age of 65.5 years. Intervention: Primary tumour management was performed in accord with multi-disciplinary team agreement. Anaesthesia and post-operative care were unaltered and provided in accord with accepted clinical practice. Main Outcomes and Measures: Three types of malignant cells detected in peripheral blood samples were enumerated and sub-typed based on the presence of chromosomal aneuploidy and immunohistochemical characteristics. To test the hypothesis that malignant cells are released by surgery, the numbers of single circulating tumour cells (CTCs), circulating tumour microemboli (CTM) and circulating endothelial cells (CTECs) were recorded pre-operatively, upon tumour removal and the second and seventh post-operative days. Results: Of a potential 88 data collection points, specimens were not obtainable in 12 instances. Tumour removal resulted in a statistically significant increase in CTCs and a non-statistically significant rise in CTMs. CTCs, CTMs and CTECs were detected in the majority of patients up to the seventh post-operative day. Individual patients demonstrated striking increases in post-operative CTCs and CTECs numbers. Conclusions/Relevance: Surgical management of OSCC has a significant impact on the systemic distribution of cancer cells. Malignant cells persisted post-operatively in a manner independent of recognised staging methods suggesting differences in tumour biology between individuals. Further investigation is warranted to determine whether circulating malignant cell enumeration can be used to refine risk stratification for patients with OSCC. Full article

Cancer is primarily a disease in which late diagnosis is linked to poor prognosis, and unfortunately, detection and management are still challenging. Circulating tumor cells (CTCs) are a potential resource to address this disease. Cell fusion, an event discovered recently in CTCs expressing carcinoma and leukocyte markers, occurs when ≥2 cells become a single entity (hybrid cell) after the merging of their plasma membranes. Cell fusion is still poorly understood despite continuous evaluations in in vitro/in vivo studies. Blood samples from 14 patients with high-grade serous ovarian cancer (A.C. Camargo Cancer Center, São Paulo, Brazil) were collected with the aim to analyze the CTCs/hybrid cells and their correlation to clinical outcome. The EDTA collected blood (6 mL) from patients was used to isolate/identify CTCs/hybrid cells by ISET. We used markers with possible correlation with the phenomenon of cell fusion, such as MC1-R, EpCAM and CD45, as well as CEN8 expression by CISH analysis. Samples were collected at three timepoints: baseline, after one month (first follow-up) and after three months (second follow-up) of treatment with olaparib (total sample = 38). Fourteen patients were included and in baseline and first follow-up all patients showed at least one CTC. We found expression of MC1-R, EpCAM and CD45 in cells (hybrid) in at least one of the collection moments. Membrane staining with CD45 was found in CTCs from the other cohort, from the other center, evaluated by the CellSearch^® system. The presence of circulating tumor microemboli (CTM) in the first follow-up was associated with a poor recurrence-free survival (RFS) (5.2 vs. 12.2 months; p = 0.005). The MC1-R expression in CTM in the first and second follow-ups was associated with a shorter RFS (p = 0.005). CEN8 expression in CTCs was also related to shorter RFS (p = 0.035). Our study identified a high prevalence of CTCs in ovarian cancer patients, as well as hybrid cells. Both cell subtypes demonstrate utility in prognosis and in the assessment of response to treatment. In addition, the expression of MC1-R and EpCAM in hybrid cells brings new perspectives as a possible marker for this phenomenon in ovarian cancer. Full article

Background: During Cardiopulmonary Bypass (CPB) gaseous micro-emboli (GMEs) decrease the quality of the blood flow and the capillary oxygen delivery, increasing the incidence of postoperative neurocognitive disorders (POCD) following cardiac surgery. In these circumstances, the use of an efficient device, could be crucial for the removal and reduction of micro-embolic activity. Methods: From February 2022 to March 2022, we prospectively collected data from 40 consecutive patients undergoing conventional and minimally invasive cardiac surgery that used the Horizon AF PLUS (Eurosets, Medolla, Italy). We collected, during the CPB’s time, the incidence of unexpected predisposing factors for micro-embolic activity reported in the literature with the GMEs count and their diameter through the GAMPT BCC 300 (Germany). Results: The group of patients without unexpected predisposing factors for micro-embolic activity (55%) reported a GME volume of 0.59 ± 0.1 (μL) in the arterial line (p-value 0.67). In both groups were no reported performance deficit during the procedures for oxygenation and CO₂ removal. Conclusions: Our clinical analysis showed that Horizon AF PLUS is an effective and safe device without iatrogenic perioperative complications, for the reduction of micro embolic activity during CPBs procedures, with high efficiency in terms of oxygenating performance and thermal exchange. Full article

Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate and death in colorectal cancer (CRC) patients. Various biomarkers have been explored in predicting CRC recurrence. This study investigated the expressions of plasma/exosomal microRNA-21 (miR-21) in 113 CRC patients by qPCR, their values of predicting CRC recurrence, and the possibility to improve the prognostic efficacy in early CRC recurrence in stratified patients by combined biomarkers including circulating miR-21s, circulating tumour cells/microemboli (CTCs/CTM), and serum carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9). Expressions of plasma and exosomal miR-21s were significantly correlated (p < 0.0001) in all and late-stage patients, presenting similar correlations with other biomarkers. However, stage IV patients stratified by a high level of exosomal miR-21 and stage I to III patients stratified by a high level of plasma miR-21 displayed significantly worse survival outcomes in predicting CRC recurrence, suggesting their different values to predict CRC recurrence in stratified patients. Comparable and even better performances in predicting CRC recurrence in late-stage patients were found by CTCs/CTM from our blood samples as sensitive biomarkers. Improved prognosing efficacy in CRC recurrence and better outcomes to significantly differentiate recurrence in stratified patients could be obtained by analysing combined biomarkers. Full article

Circulating tumor cells have a strong potential as a quasi-non-invasive tool for setting up a precision medicine strategy for cancer patients. Using a second-generation “filtration-based” technology to isolate CTCs, the Screencell™ technology (Sarcelles, France), we performed a large and simultaneous analysis of all atypical circulating tumor cells (aCTCs) isolated from the blood of metastatic breast cancer (mBC) patients. We correlated their presence with clinicopathological and survival data. We included 91 mBC patients from the PERMED-01 study. The median number of aCTCs was 8.3 per mL of blood. Three subsets of aCTCs, absent from controls, were observed in patients: single (s-aCTCs), circulating tumor micro-emboli (CTM), and giant-aCTCs (g-aCTCs). The presence of g-aCTCs was associated with shorter progression free survival and overall survival. This study highlights the heterogeneity of aCTCs in mBC patients both at the cytomorphological and molecular levels. In addition, it suggests the usefulness of the g-aCTC subset as a prognostic factor and a potential stratification tool to treat late-stage mBC patients and improve their chances of benefiting from early clinical trials. Full article

Tumor cells dissociate from the primary site and enter into systemic circulation (circulating tumor cells, CTCs) either alone or as tumor microemboli (clusters); the latter having an increased predisposition towards forming distal metastases than single CTCs. The formation of clusters is, in part, created by contacts between cell–cell junction proteins and/or cytokine receptor pairs with other cells such as neutrophils, platelets, fibroblasts, etc. In the present study, we provide evidence for an extravesicular (EV) mode of communication between pancreatic cancer CTCs and neutrophils. Our results suggest that the EV proteome of CTCs contain signaling proteins that can modulate degranulation and granule mobilization in neutrophils and, also, contain tissue plasminogen activator and other proteins that can regulate cluster formation. By exposing naïve neutrophils to EVs isolated from CTCs, we further show how these changes are modulated in a dynamic fashion indicating evidence for a deeper EV based remodulatory effect on companion cells in clusters. Full article

Circulating tumor cells (CTCs) have been recognized as a major contributor to distant metastasis. Their unique role as metastatic seeds renders them a potential marker in the circulation for early cancer diagnosis and prognosis as well as monitoring of therapeutic response. In the past decade, researchers mainly focused on the development of isolation techniques for improving the recovery rate and purity of CTCs. These developed techniques have significantly increased the detection sensitivity and enumeration accuracy of CTCs. Currently, significant efforts have been made toward comprehensive molecular characterization, ex vivo expansion of CTCs, and understanding the interactions between CTCs and their associated cells (e.g., immune cells and stromal cells) in the circulation. In this review, we briefly summarize existing CTC isolation technologies and specifically focus on advances in downstream analysis of CTCs and their potential applications in precision medicine. We also discuss the current challenges and future opportunities in their clinical utilization. Full article

The clinical relevance of circulating tumor cell clusters (CTC-clusters) in breast cancer (BC) has been mostly studied using the CellSearch^®, a marker-dependent method detecting only epithelial-enriched clusters. However, due to epithelial-to-mesenchymal transition, resorting to marker-independent approaches can improve CTC-cluster detection. Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch^®, CellSieve™ filters, and ScreenCell^® filters. In spiked-in samples, the 3 technologies showed similar recovery capability, whereas, in 19 clinical samples processed in parallel with CellSearch^® and CellSieve™ filters, filtration allowed us to detect more CTC-clusters than CellSearch^® (median number = 7 versus 1, p = 0.0038). Next, samples from 37 early BC (EBC) and 23 metastatic BC (MBC) patients were processed using ScreenCell^® filters for attaining both unbiased enrichment and marker-independent identification (based on cytomorphological criteria). At baseline, CTC-clusters were detected in 70% of EBC cases and in 20% of MBC patients (median number = 2, range 0–20, versus 0, range 0–15, p = 0.0015). Marker-independent approaches for CTC-cluster assessment improve detection and show that CTC-clusters are more frequent in EBC than in MBC patients, a novel finding suggesting that dissemination of CTC-clusters is an early event in BC natural history. Full article

(1) Background: Liquid biopsy (LB) is a novel diagnostic method with the potential of revolutionizing the prevention, diagnosis, and treatment of several solid tumors. The present paper aims to summarize the current knowledge and explore future possibilities of LB in the management of metastatic gastric cancer. (2) Methods: This narrative review examined the most recent literature on the use of LB-based techniques in metastatic gastric cancer and the current LB-related clinical trial landscape. (3) Results: In gastric cancer, the detection of circulating cancer cells (CTCs) has been recognized to have a prognostic role in all the disease stages. In the setting of localized disease, cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) qualitative and quantitative detection have the potential to inform on the risk of cancer recurrence and metastatic dissemination. In addition, gastric cancer-released exosomes may play an essential part in metastasis formation. In the metastatic setting, the levels of cfDNA show a positive correlation with tumor burden. There is evidence that circulating tumor microemboli (CTM) in the blood of metastatic patients is an independent prognostic factor for shorter overall survival. Gastric cancer-derived exosomal microRNAs or clonal mutations and copy number variations detectable in ctDNA may contribute resistance to chemotherapy or targeted therapies, respectively. There is conflicting and limited data on CTC-based PD-L1 verification and cfDNA-based Epstein–Barr virus detection to predict or monitor immunotherapy responses. (4) Conclusions: Although preliminary studies analyzing LBs in patients with advanced gastric cancer appear promising, more research is required to obtain better insights into the molecular mechanisms underlying resistance to systemic therapies. Moreover, validation and standardization of LB methods are crucial before introducing them in clinical practice. The feasibility of repeatable, minimally invasive sampling opens up the possibility of selecting or dynamically changing therapies based on prognostic risk or predictive biomarkers, such as resistance markers. Research is warranted to exploit a possible transforming area of cancer care. Full article

Circulation tumor cells (CTCs) play an important role in metastasis and highly correlate with cancer progression; thus, CTCs could be considered as a powerful diagnosis tool. Our previous studies showed that the number of CTCs could be utilized for recurrence prediction in colorectal cancer (CRC); however, the odds ratio was still lower than five. To improve prognosis in CRC patients, we analyzed CTC clusters/microemboli, CTC numbers, and carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9) levels using a self-assembled cell array (SACA) chip system for recurrence prediction. In CRC patients, the presence of CTC clusters/microemboli may have higher correlation in metastasis when compared to the high number of CTCs. Additionally, when both the number of CTCs and serum CEA levels are high, very high odds ratios of 24.4 and 17.1 are observed in patients at all stages and stage III of CRC, respectively. The high number of CTCs and CTC clusters/microemboli simultaneously suggests the high chance of relapse (odds ratio 8.4). Overall, the characteristic of CTC clusters/microemboli, CEA level, and CTC number have a clinical potential to enhance CRC prognosis. Full article

Circulating tumor microemboli (CTMs) are clusters of cancer cells detached from solid tumors, whose study can reveal mechanisms underlying metastatization. As they frequently comprise unknown fractions of leukocytes, the analysis of copy number alterations (CNAs) is challenging. To address this, we titrated known numbers of leukocytes into cancer cells (MDA-MB-453 and MDA-MB-36, displaying high and low DNA content, respectively) generating tumor fractions from 0–100%. After low-pass sequencing, ichorCNA was identified as the best algorithm to build a linear mixed regression model for tumor fraction (TF) prediction. We then isolated 53 CTMs from blood samples of six early-stage breast cancer patients and predicted the TF of all clusters. We found that all clusters harbor cancer cells between 8 and 48%. Furthermore, by comparing the identified CNAs of CTMs with their matched primary tumors, we noted that only 31–71% of aberrations were shared. Surprisingly, CTM-private alterations were abundant (30–63%), whereas primary tumor-private alterations were rare (4–12%). This either indicates that CTMs are disseminated from further progressed regions of the primary tumor or stem from cancer cells already colonizing distant sites. In both cases, CTM-private mutations may inform us about specific metastasis-associated functions of involved genes that should be explored in follow-up and mechanistic studies. Full article