Postoperative Circulating Tumor Cells Research Articles

Circulating tumor cells and tumor DNA in patients with resectable colorectal liver metastases: The MIRACLE.

3011 Background: Recurrence risk after curative surgery for colorectal liver metastases (CRLM) remains high, underlining the need for prognostic markers to detect minimal residual disease after local treatment. The aim of this study was to determine the association between recurrence-free survival (RFS) and detection of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) before and after surgical treatment of resectable CRLM. Methods: The MIRACLE isa prospective, observational biomarker study in patients with isolated, resectable CRLM without (neo)adjuvant chemotherapy, recruited between October 2015 and December 2021. The study was powered to detect at least a 20% difference in one-year recurrence rate between detectable and undetectable circulating tumor load after surgery. Blood samples were collected one day before surgery (T0) and three weeks (T3) after surgery. CTCs were enumerated using the FDA-approved CellSearch system. ctDNA before surgery was measured by next generation sequencing (NGS) using a targeted panel (Oncomine Colon cfDNA assay) and postoperatively by digital PCR (dPCR). Results: CTC enumeration resulted in positivity for 43 out of 192 patients (22%) at baseline and 14 out of 161 patients (9%) at T3. ctDNA was detected in 125 out of 191 patients (65%) at baseline, of which 25 (20%) still had detectable ctDNA at T3. Patients with postoperative undetectable CTC had a significantly improved RFS (1-year RFS: 15% vs. 51%, log-rank test p=0.009). Also, patients with postoperative undetectable ctDNA had a significantly improved RFS (1-year RFS: 20% vs. 54%, log-rank test p<0.001). In multivariable analysis, at baseline no association was found between RFS and CTCs (HR 1.01; p=0.97) or ctDNA (HR 1.29; p=0.29). In contrast, after surgery a significantly shorter RFS was observed in patients with detectable CTCs (HR 3.09; p=0.002) and ctDNA (HR 3.53; p<0.001). Postoperative ctDNA status was a stronger predictor of recurrence compared to known clinical risk factors. Conclusions: This is the first study conducted in patients with resectable CRLM without (neo)adjuvant chemotherapy, which demonstrates the impact of detectable circulating tumor load after surgery on RFS. Postoperative ctDNA and CTC detection are a strong predictor for a shorter RFS after local treatment, as opposed to preoperative ctDNA or CTC detection. [Table: see text]

Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma.

Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma. Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma. CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation. The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTM-based survival models can enable clinicians to evaluate patients' response to surgery as well as their outcomes.

Effect of various hepatectomy procedures on circulating tumor cells in postoperative patients: a case-matched comparative study.

The objective of this study is to elucidate the prevalence of systemic circulating tumor cells (CTCs) prior to and following resection of hepatocellular carcinoma (HCC), and to compare the disparities in postoperative CTCs in terms of quantity and classifications between the open liver resection (OPEN) and laparoscopic liver resection (LAP) cohorts. From September 2015 to May 2022, 32 consecutive HCC patients who underwent laparoscopic liver resection at Southwest Hospital were retrospectively enrolled in this study. The clinicopathological data were retrieved from a prospectively collected computer database. Patients in the OPEN group matched at a 1:1 ratio with patients who underwent open liver resection during the study period on age, gender, tumor size, number of tumors, tumor location, hepatitis B surface antigen (HBsAg) positivity, alpha-fetoprotein (AFP) level, TNM and Child-Pugh staging from the database of patients to form the control group. The Can-Patrol CTC enrichment technique was used to enrich and classify CTCS based on epithelial-mesenchymal transformation phenotypes. The endpoint was disease-free survival (DFS), and the Kaplan-Meier method and multiple Cox proportional risk model were used to analyze the influence of clinicopathological factors such as total CTCs and CTC phenotype on prognosis. The mean age of the 64 patients with primary liver cancer was 52.92 years (23-71), and 89.1% were male. The postoperative CTC clearance rate was more significant in the OPEN group. The total residual CTC and phenotypic CTC of the LAP group were significantly higher than those of the OPEN group (p = 0.017, 0.012, 0.049, and 0.030, respectively), which may increase the possibility of metastasis (p = 0.042). In Kaplan-Meier analysis, DFS was associated with several clinicopathological risk factors, including Barcelona Clinical Liver Cancer (BCLC) stage, tumor size, and vascular invasion. Of these analyses, BCLC Stage [p = 0.043, HR (95% CI) =2.03(1.022-4.034)], AFP [p = 0.007, HR (95% CI) =1.947 (1.238-3.062)], the number of positive CTCs [p = 0.004, HR (95% CI) =9.607 (2.085-44.269)] and vascular invasion [p = 0.046, HR (95% CI) =0.475 (0.22-1.023)] were significantly associated with DFS. In comparison to conventional OPEN technology, LAP technology has the capacity to augment the quantity of epithelial, mixed, and mesenchymal circulating tumor cells (CTCs). Following the surgical procedure, there was a notable increase in the total CTCs, epithelial CTCs, and mixed CTCs within the LAP group, indicating a potential drawback of LAP in facilitating the release of CTCs.

A Prospective Long-Term Follow-Up Study: The Application of Circulating Tumor Cells Analysis to Guide Adjuvant Therapy in Stage II Colorectal Cancer.

The efficacy of circulating tumor cells (CTCs) in the selection of stage II colorectal cancer (CRC) patients for adjuvant chemotherapy remains inconclusive. The aim of this study was to validate the necessity of adjuvant chemotherapy for stage II CRC patients with positive postoperative CTCs. The clinicopathological features and overall survival (OS) of a cohort of 70 patients with confirmed CRC were collected and analyzed. The total rate of positive CTCs was 55.7%, while the average OS was 70.8months and the OS rate was 75.7% (53/70). These 70 patients were divided into four subgroups, including a CTC-negative group with non-adjuvant chemotherapy (CHEMO-/CTC-) versus a CTC-positive group with non-adjuvant chemotherapy (CHEMO-/CTC+), CHEMO+/CTC- versus CHEMO+/CTC+, CHEMO-/CTC- versus CHEMO+/CTC-, and CHEMO+/CTC+ versus CHEMO-/CTC+; the total numbers in each subgroup were 25 versus 32, 6 versus 7, 25 versus 6, and 7 versus 32, respectively. The average OS of the CHEMO-/CTC- and CHEMO-/CTC+ groups was 82.0 and 68.1months, respectively (p = 0.020); the average OS of the CHEMO+/CTC- and CHEMO+/CTC+ groups was 83.6months and 76.4months, respectively (p = 0.963); the average OS of the CHEMO-/CTC- and CHEMO+/CTC- groups was 82.0months and 83.6months, respectively (p = 0.999); and the average OS of the CHEMO+/CTC+ and CHEMO-/CTC+ groups was 76.4months and 68.1months, respectively (p = 0.247). Positive CTCs are a potential prognostic marker for stage II CRC.

Monitoring with circulating tumor cells in the perioperative setting of patients with surgically treated stages I-IIIA NSCLC.

Surgery is regarded as the treatment's cornerstone for early stage and locally advanced non-small cell lung cancer (NSCLC) whenever the tumor is considered resectable. Liquid biopsy is one of the most promising research areas in oncology in the last 10 years, providing a useful non-invasive tool to detect and monitor cancer. The prognostic value of circulating tumor cells (CTCs) has been studied in different cancer types and had been related with a higher risk of relapse and worse prognosis. The aim of this study is to evaluate the prognostic value of CTC detection in patients with stage I-IIIA NSCLC treated with surgery. We conducted a prospective, single-center study of 180 consecutive patients with resected and pathological confirmed stage I to IIIA (TNM AJCC/UICC 8th edition) NSCLC. Patients' blood samples were processed and CTCs were characterized before and after the surgery. A cohort of patients had CTC determination after chemotherapy and surgery. Cut-off points were established in 1 and 5 CTCs for statistical analysis. A proportion of 76.7% had at least 1 CTC before the surgery, and 30.6% had 5 or more, while 55.9% had at least 1 CTC after surgery, and 8.3% had 5 or more. We found no correlation between preoperative CTC detection for a cut-off of 5 with neither overall survival (OS) [hazard ratio (HR): 0.99, P=0.887], disease-free survival (DFS) (HR: 0.95, P=0.39) nor relapse (32.7% vs. 28.8%, P=0.596). We also did not find a correlation between postoperative CTCs detection for a cut-off of 5 with either OS (HR: 1.01, P=0.808), DFS (HR: 0.95, P=0.952) or relapse (26.7% vs. 29.5%, P=0.83). The mean change in the number of CTCs over time between preoperative and postoperative samples was 2.13, with a standard deviation of 6.78. Despite the large cohort of patients included in this study, CTC monitoring in the perioperative setting was not correlated with relapse, DFS or OS in our study, and therefore cannot be recommended as a reliable biomarker for minimal residual disease (MRD) after surgery.

Perioperative change of circulating tumor cells in cytoreductive radical prostatectomy for oligometastatic hormone-sensitive prostate cancer: the preliminary safety evidence from long-term oncologic outcomes.

Surgical manipulation has a risk of triggering the shedding of circulating tumor cells (CTCs) in patients with malignancies, However, perioperative change of circulating tumor cells in cytoreductive radical prostatectomy (CRP) for patients with oligometastatic hormone-sensitive prostate cancer (omHSPC) has not yet been well documented. This study aimed to assess whether CRP is a safe procedure for patients with omHSPC by monitoring the perioperative change of CTCs and investigating its impact on long-term oncologic outcomes. We have observed a significant decrease between the median CTC counts before and after surgery (6 vs. 4, p = 0.026). Comparing preoperative and postoperative CTC levels, seven patients increased (CTC increase group), one did not change and nineteen decreased (CTC non-increase group). PSA response rates in CTC increase group were lower than those in CTC non-increase group (73.0% vs 99.8%, p = 0.162), and nadir PSA was higher in CTC increase group (0.043 vs 0.003, p = 0.072). The CTC increase was positively correlated with the nadir PSA (r = 0.386, p = 0.047). The median follow-up period was 71.6months, we found that there was no significant difference in clinical-pathological, operative variables or long-term oncologic outcomes between perioperative CTC increase and non-increase groups. In the entire cohort, the CTC level significantly decreased after surgery. There was no significant differences in long-term oncologic outcomes between the CTC increase and non-increase groups, implying that CRP potentially represents a safe procedure for the treatment of patients with omHSPC. The results need to be confirmed in a prospective large-scale clinical trial.

Influence of opioid analgesia type on circulating tumor cells in open colorectal cancer surgery (POACC-1): study protocol for a prospective randomized multicenter controlled trial

BackgroundOpioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet.MethodsWe intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2–4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development.DiscussionThe mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies.Trial registration numberNCT03700411, registration date: October 3, 2018. Study status: recruiting.

The mesenchymal circulating tumor cells as biomarker for prognosis prediction and supervision in hepatocellular carcinoma

PurposeHepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. Accurate prognosis prediction tools are urgently needed. While the use of circulating tumor cells (CTCs) as prognostic prediction tool has a clear potential.MethodsWe established a comprehensive, negative enrichment-based strategy for CTCs analysis in patients with HCC, involving identification of epithelial CTCs (E-CTCs) and mesenchymal CTCs (M-CTCs) through specific biomarker. This strategy was performed in 127 HCC cases, 21 nonmalignant liver disease (NMLD) patients and 42 health control to analyze the relevance between CTCs and tumor recurrence.ResultsThe total CTC number and M-CTC percent were positively correlated with tumor malignancy and high recurrence risk. Individually, preoperative total CTC number and M-CTC percent could robustly distinguish relapse cases from those with no relapse, with sensitivity of 80.95% and 90.48%, specificity of 74.12% and 84.71%, respectively. Levels of preoperative total CTC number and M-CTC percent can both be regarded as independent risk factors for HCC with early recurrence (P = 0.0053, P < 0.0001), and are both significantly correlated with worse recurrence-free survival (RFS) (log rank P < 0.0001; HR 7.78, 95% CI = 3.59–16.87; log rank P < 0.0001; HR 24.4, 95% CI = 8.67–68.77). The levels of total CTC number and M-CTC number had higher effectiveness than alpha fetal protein (AFP) in HCC longitudinal supervision (77.78% vs 88.89% vs 22.22%).ConclusionPreoperative and postoperative CTCs with higher effectiveness than AFP in prognosis prediction and recurrence supervision, indicating that CTCs could work as the biomarker for HCC clinical management.

Circulating Tumor Cells as a Predictive Biomarker in Resectable Lung Cancer: A Systematic Review and Meta-Analysis.

In breast, prostate, and other epithelial tumors, circulating tumor cells (CTC) in peripheral blood may predict survival. Our study evaluated the prognostic significance of baseline and postoperative CTC in patients with early non-small cell lung cancer (NSCLC) through a meta-analytic approach. Prospective studies comparing survival outcomes between positive (CTC+) and negative CTC (CTC-) patients were systematically searched. Primary outcomes were overall (OS) and disease-free survival (DFS) with hazard ratio (HR) and 95% confidence interval (CI) as the effect measure. Pooled HR determined the prognostic role under a fixed-effect or random-effect model depending on heterogeneity. Eighteen studies with 1321 patients were eligible. CTC+ patients were associated with an increased risk of death (HR 3.53, 95% CI 2.51-4.95; p &lt; 0.00001) and relapse (HR 2.97, 95% CI 2.08-4.22; p &lt; 0.00001). Subgroup analysis results were consistent in different subsets, including time points (baseline and postoperative) and sources (peripheral and pulmonary vein) of blood collection, detection methods (label-free, label-dependent, and RT-PCR), and follow-up duration. Our meta-analysis revealed that CTC is a promising predictive biomarker for stratifying survival outcomes in patients with early-stage NSCLC. However, future studies are required to validate these findings and standardize detection methods.

Circulating tumor cells correlating with Ki-67 predicts the prognosis of bladder cancer patients

PurposeTo investigate the value of circulating tumor cells (CTCs) and Ki-67 in predicting the prognosis of bladder cancer. Here, we tested CTC counts and Ki-67 levels to assess patient prognosis.Methods84 patients with bladder cancer who underwent surgery were included in this study. Peripheral blood CTCs were detected by SE-iFISH technology before and after surgery, and Ki-67 levels were analyzed by immunohistochemistry. The association between CTCs and Ki-67 and the combination of the two was analyzed to predict the prognosis of patients.Results76 out of 84 patients (90.5%) were positive. ROC curve analysis showed that preoperative and postoperative CTC counts = 4 and 2 were the best thresholds for predicting patient recurrence or death. In multivariate analysis, high postoperative CTC count (≥ 2) (P < 0.001) and Ki-67 high expression (≥ 15%) (P < 0.001) were independent poor prognostic factors for PFS in bladder cancer patients. In addition, the study found that Ki-67 levels were positively correlated with high postoperative CTC counts, Bladder cancer patients with Ki-67 high expression and high postoperative CTC counts were associated with extremely poor progression-free survival.ConclusionKi-67 high expression is associated with high postoperative CTC counts, both of which predict poor prognosis in bladder cancer patients.

Predictive Value of Circulating Tumor Cells Based on Subtraction Enrichment for Recurrence Risk in Stage II Colorectal Cancer.

Current guidelines recommend adjuvant chemotherapy (ACT) for stage II colorectal cancer (CRC) patients by using clinical high risk factors, with which circulating tumor cells (CTCs) were not considered. Here, an assessment to detect CTCs based on subtraction enrichment mediated by magnetic beads conjugated with CD45, immunofluorescence staining of CK, and fluorescence in situ hybridization of CEP8 is established. Both CEP8- and CK-positive CTCs have the potential to improve the risk stratification of stage II CRC patients. Patients with preoperative CTCs of ≥4 had a significantly higher recurrence risk than those with preoperative CTCs of <4 in two external validation cohorts (P < 0.0001). In the subgroup with clinical high risk, when preoperative CTCs were <4, patients did not benefit from ACT (P = 0.5764); however, when preoperative CTCs were ≥4, patients received benefit from ACT (P = 0.0064). Additionally, regardless of clinical risk status and preoperative CTC levels, if postoperative CTC levels were ≥4 for more than three consecutive time points (monitoring time interval, 2-6 months), the recurrence rate was 100%. Our findings suggested that the subtraction enrichment of CTCs could provide a reliable method to stratify the recurrence risk and make therapeutic decisions after surgery in stage II CRC patients.

Early ligation of the pulmonary vein can reduce the dissemination of shed tumor cells during thoracoscopic lobectomy

ObjectiveThe sequence of vessel ligation in lobectomy can significantly affect the hematogenous spread of circulating tumor cells (CTCs). Vein-first ligation substantially reduces CTC dissemination and achieves favorable survival compared with artery-first ligation. In this study, we further explored whether the timing of pulmonary vein (PV) ligation determined according to the early and late PV ligation technique is associated with CTC dissemination. MethodsA total of 44 patients who underwent uniform 2-port video-assisted thoracoscopic surgery lobectomy were enrolled; the subjects were divided into the early ligation group (n = 18) and late ligation group (n = 26) according to whether PV ligation was prioritized during surgery. PV blood was obtained before PV ligation and after lobe resection. CTCs were detected using telomerase reverse transcriptase-based CTC detection and validated using FlowSight and fluorescence in situ hybridization. ResultsThe median postoperative PV CTC (Post-PVCTC) count was 9 (interquartile range [IQR], 6-18), which was higher than the median preoperative PV CTC (Pre-PVCTC) count of 1 (IQR, 0-3; P < .001). Clinicopathologic correlation analysis showed that the Pre-PVCTC count correlated positively with TNM stage (P = .002) and lymph node metastasis (P = .002) and that the Post-PVCTC count correlated positively with tumor density (P = .043) and vessel/lymphatic invasion (P < .030). Interestingly, although no statistical difference in the median Pre-PVCTC count was observed, the median Post-PVCTC count in the early ligation group was 16 (IQR, 9.5-36.75), whereas that in the late ligation group it was 8 (IQR, 4.75-12.25), showing a significant difference (P = .004). ConclusionsWe provide the first evidence to show that early PV ligation can prevent PVCTCs from spreading into the circulation, offering an innovative surgical concept for the principle sequence of pulmonary vessel management.

Circulating Tumor Cells and the Non-Touch Isolation Technique in Surgery for Non-Small-Cell Lung Cancer.

Simple SummaryOur review discusses findings for the non-touch isolation technique in surgery, especially in surgery for non-small-cell lung cancer. This technique aims to prevent the release of circulating tumor cells (CTCs) from the tumor nest to the bloodstream during surgery, but its efficacy has not been clearly verified. We have summarized the history of CTC detection, relevance of CTCs to clinical practice, and evidence regarding this technique for lung cancer surgery.Circulating tumor cells (CTCs) are dislodged from the primary tumor into the bloodstream, travel within the bloodstream to distant organs, and finally extravasate and proliferate as epithelial metastatic deposits. The relationship between the existence of CTCs and tumor prognosis has been demonstrated by many researchers. In surgery for malignancies, the surgical manipulation of tumors and tissues around the tumor may lead to the release of CTCs into the bloodstream. The non-touch isolation technique (NTIT) has been advocated to prevent the release of CTCs during surgery. The concept of NTIT is the prevention of intraoperative increment of CTCs from the primary tumor by the early blockade of outflow vessels, and ‘pulmonary vein (PV)-first lobectomy’ during surgery for non-small-cell lung cancer (NSCLC) corresponds to this technique. The concept of PV-first lobectomy is well known among thoracic surgeons, but evidence of its efficacy for preventing the increase of intra- and postoperative CTCs and for improving postoperative prognosis is still uncertain. Our study summarizes evidence regarding the relationship between NTIT and CTCs in NSCLC and suggests the need for further research on CTCs and CTC-detecting modalities.

Prognostic Role of Circulating Tumor Cells in Resectable Colorectal Liver Metastases

Background: A systematic review and meta-analysis was performed to assess the prognostic role of preoperative, intraoperative, and postoperative circulating tumor cells (CTC) in resectable colorectal liver metastases (CRLM). Methods: The following databases were searched in May 2021: Medline, Embase, Biosis, Cochrane, Web of Science, and clinicaltrials.gov. Resectable CRLM where CTC was detected using CellSearch® (FDA approved) or RT-PCR was included. A random-effects model was used for pooled and subgroup analyses of Disease-Free Survival (DFS) and Overall Survival (OS). Surgical resections performed for palliative purposes were excluded. Randomized and non-randomized clinical trial, and cohort studies were included. Hazard ratio (HR) along with confidence interval (CI) were extracted or calculated using the Tierney method. Study bias was assessed using the Newcastle-Ottawa (NOS) scale. Results: 10 studies (801 patients) were identified for qualitative analysis (Table 1). 9 studies (781 patients) were included in the pooled analysis, out of which 6 studies detected CTC using CellSearch®. Two studies were high quality based on NOS. There was no statistical difference in DFS in patients with preoperative CTC (HR 1.97; 95% CI 0.85 – 4.57), intraoperative CTC (HR 3; 95% CI 0.98 – 9.21), and postoperative CTC (HR 1.93, 95% CI 0.82 – 4.57) detected in peripheral blood with CellSearch®. The OS was worse in patients with preoperative CTC (HR 2.36, 95% CI 1.15 – 4.84) (Figure 1) but similar in patients with intraoperative CTC (HR 2.33, 95%, 0.79 – 6.83). Conclusion: Preoperative CTC detected in peripheral blood using CellSearch® may predict OS in patients undergoing liver resection for CRLM.

The Effect of Different Surgical Methods on the Number of Circulating Tumor Cells in the Peripheral Blood of Patients with Renal Cell Carcinoma

Objective: The objective is to explore the effects of different surgical methods-retroperitoneal laparoscopic radical nephrectomy (RLRN) and open radical nephrectomy (ORN) on the number of circulating tumor cells (CTC) in the peripheral blood of patients with renal cancer. Methods: The clinical data of 63 patients in the Department of Urology, Affiliated Hospital of Chengde Medical College who underwent radical surgery for renal cancer were divided into CTC positive group (18 cases of open surgery and 16 cases of minimally invasive surgery) and CTC negative group (14 cases of open surgery), 15 cases of minimally invasive surgery), overall group (32 cases of open surgery, 31 cases of minimally invasive surgery). Observe the changes in the number of CTC 1 week before operation and 1 week after operation. Results: In the positive group, whether it was open surgery or minimally invasive surgery, the postoperative CTC level of patients was significantly reduced (P surgery (P 0.05). In the overall group, both open and minimally invasive surgery CTC decreased significantly, and the difference was statistically significant (P Conclusion: The two different surgical methods can reduce the level of CTC, but compared with ORN, RLRN can significantly increase the number of postoperative CTC. Patients in the CTC-negative group may be less suitable for minimally invasive surgery. CTC levels have certain potential in the selection and guidance of treatment modes for patients with renal cell carcinoma (RCC).

Telomerase-positive circulating tumor cells are associated with poor prognosis via a neutrophil-mediated inflammatory immune environment in glioma

BackgroundGliomas are the most common aggressive cancer in the central nervous system. Considering the difficulty in monitoring glioma response and progression, an approach is needed to evaluate the progression or survival of patients with glioma. We propose an application to facilitate clinical detection and treatment monitoring in glioma patients by using telomerase-positive circulating tumor cells (CTCs) and to further evaluate the relationship between the immune microenvironment and CTCs in glioma patients.MethodsFrom October 2014 to June 2017, 106 patients newly diagnosed with glioma were enrolled. We used the telomerase reverse transcriptase CTC detection method to detect and analyze the CTC statuses of glioma patients before and after surgery. FlowSight and FISH confirmed the CTCs detected by the telomerase-based method. To verify the correlation between CTCs and the immune response, peripheral white blood cell RNA sequencing was performed.ResultsCTCs were common in the peripheral blood of glioma patients and were not correlated with the pathological classification or grade of patients. The results showed that the presence of postoperative CTCs but not preoperative CTCs in glioma patients was a poor prognostic factor. The level of postoperative CTCs, which predicts a poor prognosis after surgery, may be associated with neutrophils. RNA sequencing suggested that postoperative CTCs were positively correlated with innate immune responses, especially the activation of neutrophils and the generation of neutrophil extracellular traps, but negatively correlated with the cytotoxic response.ConclusionsOur results showed that telomerase-positive CTCs can predict a poor prognosis of patients with glioma. Our results also showed a correlation between CTCs and the immune macroenvironment, which provides a new perspective for the treatment of glioma.

Perioperative Circulating Tumor Cells (CTCs), MCTCs, and CTC-White Blood Cells Detected by a Size-Based Platform Predict Prognosis in Renal Cell Carcinoma.

To explore the clinical significance of the perioperative counts of circulating tumor cells (CTCs), mesenchymal CTCs (MCTCs), and CTC- white blood cells (WBCs) in renal cell carcinoma patients. A total of 131 patients with renal cancer who underwent operation excision from our hospital were enrolled. In addition, 20 patients with benign renal diseases were recruited as a control. Blood samples were collected from the 131 patients, before operation and 3 months after surgery. Samples were also obtained simultaneously from the control group. CanPatrol CTC detection technique was used to enrich and identify CTCs, MCTCs, and CTC-WBCs. All enrolled patients were T1-3N0M0. From these, 52 patients with renal cancer underwent radical resection, while other 79 patients underwent nephron-sparing surgery. The positive rate of CTC, MCTC, and CTC-WBC before surgery were 95.4% (125/131), 61.1% (80/131), and 11.5% (15/131), respectively. Preoperative total CTCs, MCTCs, or CTC-WBCs were poorly correlated with patients' parameters. Preoperative CTC, MCTC, or CTC-WBC showed no association with progression-free survival (PFS). In contrast, postoperative total CTCs (≥6), positive MCTCs, and positive CTC-WBCs significantly correlated with recurrence and metastasis. These results remained independent indicators for worse PFS. In addition, the increased CTC and MCTC count after surgery also correlated with unfavorable PFS. The detection of six or more total CTCs, MCTC, or CTC-WBCs in peripheral blood after surgery might help to identify a subset of patients that have higher recurrent risk than the overall population of patients with at different stages of renal cancer.

Longitudinal Analysis of Circulating Tumor Cells in Colorectal Cancer Patients by a Cytological and Molecular Approach: Feasibility and Clinical Application.

IntroductionLiquid biopsies allowing for individualized risk stratification of cancer patients have become of high significance in individualized cancer diagnostics and treatment. The detection of circulating tumor cells (CTC) has proven to be highly relevant in risk prediction, e.g., in colorectal cancer (CRC) patients. In this study, we investigate the clinical relevance of longitudinal CTC detection over a course of follow-up after surgical resection of the tumor and correlate these findings with clinico-pathological characteristics.MethodsIn total, 49 patients with histologically proven colorectal carcinoma were recruited for this prospective study. Blood samples were analyzed for CTC presence by two methods: first by marker-dependent immunofluorescence staining combined with automated microscopy with the NYONE® cell imager and additionally, indirectly, by semi-quantitative Cytokeratin-20 (CK20) RT-qPCR. CTC quantification data were compared and correlated with the clinico-pathological parameters.ResultsDetection of CTC over a post-operative time course was feasible with both applied methods. In patients who were pre-operatively negative for CTCs with the NYONE® method or below the cut-off for relative CK20 mRNA expression after analysis by PCR, a statistically significant rise in the immediate post-operative CTC detection could be demonstrated. Further, in the cohort analyzed by PCR, we detected a lower CTC load in patients who were adjuvantly treated with chemotherapy compared to patients in the follow-up subgroup. This finding was contrary to the same patient subset analyzed with the NYONE® for CTC detection.ConclusionOur study investigates the occurrence of CTC in CRC patients after surgical resection of the primary tumor and during postoperative follow-up. The resection of the tumor has an impact on the CTC quantity and the longitudinal CTC analysis supports the significance of CTC as a prognostic biomarker. Future investigations with an even more extended follow-up period and larger patient cohorts will have to validate our results and may help to define an optimal longitudinal sampling scheme for liquid biopsies in the post-operative monitoring of cancer patients to enable tailored therapy concepts for precision medicine.

Telomerase Positive Circulating Tumor Cells Associated with Poor Prognosis &lt;i&gt;via&lt;/i&gt; Neutrophil-Mediated Inflammatory Immune Environment in Glioma

Purpose: Considering the poor prognosis of gliomas and the difficulty in monitoring glioma response and progression, circulating tumor cells (CTCs) detection could reflect the recurrence and metastasis of glioma patients and provide more accurate information for individual treatment and prognosis prediction. Experimental Design: From October 2014 to June 2017, 106 patients newly diagnosed with glioma were enrolled. We used the telomerase reverse transcriptase CTC detection method to detect (TBCD) and analyze the preoperative and postoperative CTC statuses of glioma patients. FlowSight and FISH confirmed the CTCs detected by TBCD. To verify the correlation between CTCs and the peripheral immune environment RNA sequencing was performed. Results: CTCs were common in the peripheral blood of glioma patients, and their count was not correlated with the pathological classification or grade of patients. The survival analysis results showed that the presence of postoperative CTCs, but not preoperative CTCs, in glioma patients was a poor prognostic factor. RNA sequencing suggested that postoperative CTCs were positively correlated with peripheral innate immune responses, especially the activation of neutrophils and the generation of neutrophil extracellular traps (NETs), but negatively correlated with the cytotoxic response, especially the T cell cytotoxic response. Conclusions: Our results showed that CTCs detected by TBCD can predict a poor prognosis of gliomas. In addition, the poor prognosis may be the result of CTCs combined with systemic inflammatory immunity, especially the neutrophils activation. Funding Statement: This research was funded by the National Key R & D Program of China (2019YFC1315702), and the National Natural Science Foundation of China (81472013). Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: Peripheral blood collections were approved by the ethics committee of Cancer Hospital, Chinese Academy of Medical Sciences.

Preoperative circulating tumor cells to predict microvascular invasion and dynamical detection indicate the prognosis of hepatocellular carcinoma

BackgroundThis study explored the diagnostic power of preoperative circulating tumor cells (CTCs) for the presence of microvascular invasion (MVI) and the relationship between dynamic changes in postoperative CTCs and prognosis.MethodsA total of 137 patients were recruited for the study. Preoperative blood samples were collected from all patients to detect CTCs. The time points for blood collection were before the operation, during the operation, and at 1 week, 1 month, 2 months, 3 months, 6 months, and 1 year after surgery. The predictive power of CTC count for the presence of MVI was analyzed by receiver operating characteristic (ROC) curve analysis. According to recurrence status, 137 patients were divided into three groups: no recurrence, early recurrence, and non-early recurrence groups.ResultsA threshold CTC count of 5 showed the most significant power for predicting the existence of MVI. In multivariate analysis, the parameters of preoperative CTC count, alpha-fetoprotein (AFP) and tumor diameter were independent predictors of MVI (P < 0.05). A CTC count greater than or equal to 5 had better predictive value than AFP > 400 μg/L and tumor diameter > 5 cm. The number of intraoperative CTCs in the three groups did not increase compared to that before surgery (P > 0.05). The number of CTCs in the nonrecurrence group and the non-early recurrence group decreased significantly 1 week after surgery compared with the intraoperative values (P < 0.001), although there was no significant difference in the early recurrence group (P = 0.95). Patients with mean CTC count ≥5 had significantly worse long-term outcomes than those with mean CTC count < 5 (P < 0.001).ConclusionThe preoperative CTC counts in the peripheral blood of patients with HCC are closely correlated with MVI. The intraoperative manipulation of the lesion by the surgeon does not increase the number of CTCs in peripheral blood. Surgical removal of the tumor decreases the number of CTCs. The persistence of CTCs at a high level (≥ 5) after surgery suggests a risk of early recurrence.Clinical trial registrationRegistration number is ChiCTR-OOC-16010183, date of registration is 2016-12-18.