Role of presurgery circulating cancer cells (CTCs) as a potential pronostic factor in patients (pts) with liver surgery (LS) of colorectal cancer (CRC) metastases (M).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 518-518
Author(s):  
Lucia Teijeira ◽  
Antonio Viúdez ◽  
Maria L. Antelo ◽  
Antonio Tarifa ◽  
Cruz Zazpe ◽  
...  
Keyword(s):  
Independent Predictor ◽  
Primary Tumour ◽  
Neoadjuvant Treatment ◽  
Wild Type ◽  
Cellsearch System ◽  
Future Studies ◽  
Circulating Cancer Cells ◽  
Kras Status

518 Background: Kinetic behavior of perioperative CTCs in pts with liver CRC M has been little explored. The aim of this study was to quantified CTCs performance before, just performed and 3 months after radical LS in pts with CRC M and analyzed the surrogate role of CTCs determinations in DFS and OS. Methods: 7.5 ml of blood were drawn in CellSave tubes. CTCs were enumerated before, just performed and 3 months after radical LS. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex/Immunicon Corp.) Results: From February 2009 to August 2011, 30 pts with LS of CRC M were included. Median age was 59 (45-75); 63.3 % men. Kras status: 63.2% wild-type and 36.8% mutated; 46.7% with synchronous disease. Fong-Criteria (FC) distribution: 30% pts with 1 FC, 36.7% pts with 2 FC and 33.3% pts with 3 FC, of whom 56.7% received neoadjuvant (76.4% fluoropirimidines-based; 29% cetuximab-based; 47% bevacizumab-based) and 73.3% adjuvant treatment. PR and SD were observed in 68.8% and 31.3% of pts, respectively (100% DCR). In 83% of cases, limited LS were done (79.3% R0, median M resected: 2), 20% of pts with synchronous surgery of primary tumour. Of the 15 pts analysed, pCR were observed in 2 (13.3%) with 6 other pts (40%) with major pathological response. With a median of follow-up of 21 months, progression disease occurred in 9 pts (55.6% with liver progression), and 4 pts died. Median CTCs was 0 before (0-2: 85%; ≥3: 14.8%), just performed (0-2: 78%; ≥3: 21%) and 3 months after surgery (0-2: 94.1%; ≥3: 5.9%). DFS for pts with pre-surgery CTCs ≥3 was 10 months, and not reached for 0-2 CTCs group. OS has not been achieved in any CTCs group. In the multivariate analysis, with FC and pre-surgery CTCs, pre-surgery CTCs ≥3 tends to be an independent predictor of outcome (HR: 2.83; CI:0.53-15). Conclusions: Independently of neoadjuvant treatment, pre-surgery CTCs levels ≥3 could be a surrogate of short DFS in pts with LS of CRC M. Our study shown a slight increase in CTCs quantification after LS, instead a significant CTCs decrease was observed after adjuvant therapy. Role of radical LS in kinetic of CTCs should continue to be analysed in future studies.

Surrogate role of kinetic of perioperative circulating cancer cells (CTCs) in patients with liver metastases (M) of colorectal cancer (CRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21086-e21086
Author(s):  
Lucia Teijeira ◽  
Antonio Viudez ◽  
Maria L Antelo ◽  
Antonio Tarifa ◽  
Cruz Zazpe ◽  
...  
Keyword(s):  
Pathological Response ◽  
The Other ◽  
Kinetic Behavior ◽  
Wild Type ◽  
Cellsearch System ◽  
Future Studies ◽  
Circulating Cancer Cells ◽  
Kras Status

e21086 Background: Kinetic behavior of perioperative CTCs in pts with liver CRC M has been little explored. The aim of this study was to quantified CTCs performance before/just performed and 3 months after radical liver surgery (LS) in pts with CRC M and analyzed the surrogate role of CTCs determinations in DFS and OS. Methods: 7.5 ml of blood were drawn in CellSave tubes. CTCs were isolated and enumerated before/just perfomed and 3 months after radical LS. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex®/Immunicon Corp.) Results: From February 2009 to December 2011, 35 pts were included. Median age was 61 (45-77); 53.7 % men. Kras status: 66.7% wild-type and 33.3% mutated; 48.6% with synchronous disease. Fong-Criteria (FC) distribution: 31.4% pts with 1 FC, 37.1% pts with 2 FC and 31.4% pts with 3 FC, of whom 60% received neoadjuvant (90% fluoropirimidines-based; 33.3% cetuximab-based; 38% bevacizumab-based) and 77.1% adjuvant treatment. PR and SD were observed in 60% and 40% of pts, respectively. In 70.7% of cases, limited LS were done (68.3% R0, median metastases resected:3) Of the 17 pts analysed, pCR were observed in 2 (12%) with 7 other pts (41%) with major pathological response. With a median of follow-up of 20 months (media 21.3; 95% CI:17.3-41.4) progression disease occurred in 13 pts (55.6% with liver progression), and 5 pts died. Median CTCs was 1 before (0-2: 76%; ≥3: 24%) and just performed surgery (0-2: 65%; ³3: 35%) and 0 in the 3 months determination (0-2: 94.1%; ³3: 5.9%). In the presurgery analysis, DFS was 15 months for the CTCs ≥3 group and 33 months for <3 CTCs (HR: 0.95; 95% CI:0.34-2.64) while in the postsurgery analysis, DFS was 13 months in CTCs ≥3 group and 33 months for <3 CTCs (HR: 1.11; 95% CI:0.37-3.29) CTCs ≥3 group after surgery, OS was 33 months, not having reached in the other groups. Conclusions: There is a marked difference in DFS in favor of pts with CTCs levels 0-2 before and just performed surgery. Our study shows a slight increase in CTCs quantification after LS, instead a significant CTCs decrease was observed after adjuvant therapy. Role of radical LS in kinetic of CTCs should continue to be analysed in future studies.

scholarly journals The Prognostic Role of Anemia in Heart Failure Patients

2020 ◽  
Vol 71 (1) ◽  
pp. 185-191
Author(s):  
Tudor Parvanescu ◽  
Bogdan Buz ◽  
Diana Aurora Bordejevic ◽  
Florina Caruntu ◽  
Mihai Trofenciuc ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Condition ◽  
Independent Predictor ◽  
Univariate Analysis ◽  
Hemoglobin Concentration ◽  
Prognostic Role ◽  
Heart Failure Patients ◽  
Length Of Hospitalization

Anemia is frequently observed in heart failure (HF) patients. The aim of this prospective study was to assess if it is an independent predictor of outcome or a marker of a worse clinical condition in these patients. The study included 134 heart failure patients aged over 18 years. The patients were divided into two groups, according to the presence or absence of anemia at hospital admission. Anemia was defined as a hemoglobin concentration of less than 12 g/dl for women and less than 13 g/dl for men. The endpoints were: length of hospitalization, all cause-death during hospitalization, and all-cause death and HF rehospitalizations at 1 year. Anemia occurred in 33% of HF patients. The HF patients with anemia were significantly older, had more often ischemic etiology of heart failure and atrial fibrillation, chronic kidney disease and 3 or more comorbidities. The length of hospitalization was similar between the two groups. Deaths during hospitalization occurred in 13% of anemic and in 3% of the nonanemic patients (P=0.04). During the 1- year follow-up, 45% of the anemic vs. 28% of the nonanemic patients were rehospitalized due to aggravated HF (P=0.04), and 14% of the anemic vs 20% of the nonanemic patients died (P=0.38). Anemia was strongly predictive for in-hospital and 1- year all-cause deaths in univariate analysis, but not in multivariate analysis. Anemia seems more a marker of a worse clinical condition, rather than an independent risk factor in HF.

Exosomes as novel prognostic biomarker in potentially resectable colorectal cancer liver metastatic (CCLM) patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3558-3558
Author(s):  
Ina Valeria Zurlo ◽  
Mariantonietta Di Salvatore ◽  
Donatella Lucchetti ◽  
Filomena Colella ◽  
Claudio Ricciardi Tenore ◽  
...  
Keyword(s):  
Liver Surgery ◽  
Scoring Systems ◽  
Aggressive Approach ◽  
Post Surgery ◽  
Mutational Status ◽  
Kras Status ◽  
The One ◽  
Major Hepatectomies

3558 Background: Target therapies and new surgical strategies deeply modify the history of CCLM patients (pts). Several prognostic scoring systems have been developed but no one is able to identify pts who should be excluded from a potentially useless surgery. Currently research is committed in identifying early biomarkers able to discern pts who could benefit from an aggressive approach. Exosomes are arising as promising biomarkers in cancer. The aim of this pivotal study was to analyze the association among exosome levels during CCLM-pts treatment, clinical outcomes and the KRAS status. Methods: We enrolled 22 pts with CCLM candidate to preoperative chemotherapy (pCT) and subsequent liver surgery. A blood sample was collected before pCT, after surgery, monthly during follow-up and at progression (PD). Exosomes were isolated by ultracentrifugation and characterized by standard methods. Exosomes concentration was assessed by Bradford assay. We adopted ddPCR™ KRAS G12/G13 Screening Kit to evaluate the KRAS status in exosomal DNA (e-DNA). Results: 22 CCLM pts received pCT and underwent liver surgery: 5 major hepatectomies and 17 multiple liver resections. Changes in exosomes plasma levels were found to correlate with each treatment step,resulting reduced after pCT and surgery and increased at PD, respectively (p = 0.0026). Pts with higher baseline exosome levels experimented shorter PFS than those with lower levels (p = 0.0033 HR 0.2). No association was found between exosome levels after liver surgery and disease free interval nor overall survival. KRAS status on e-DNA was evaluated on 10 pts in baseline, in pCT, after surgery, and in PD samples. In 8 out of 10 pts e-DNA displayed the same mutational status than the one detected on tumor DNA. Changes in e-DNA KRAS copies were found statistically significant in pCT vs surgery and pCT vs PD (p = 0.039; p = 0.04). Conclusions: Our study suggests a prognostic role of exosome levels in CCLM pts. Moreover, we showed that KRAS mutational status could be monitored during the post-surgery follow up by analyzing e-DNA. Overall, our data confirm the potential role of exosomes in liquid biopsy tool to monitor molecular changes during the treatment of CCLM pts.

scholarly journals Central Nervous System–Targeted Complement Inhibition Mediates Neuroprotection after Closed Head Injury in Transgenic Mice

2003 ◽  
Vol 23 (9) ◽  
pp. 1070-1074 ◽  
Author(s):  
Mario Rancan ◽  
Maria C. Morganti-Kossmann ◽  
Scott R. Barnum ◽  
Silvia Saft ◽  
Oliver I. Schmidt ◽  
...  
Keyword(s):  
Head Injury ◽  
Transgenic Mice ◽  
Closed Head Injury ◽  
Wild Type ◽  
Complement Inhibition ◽  
Future Studies ◽  
Closed Head ◽  
Targeted Expression ◽  
The Complement System

The role of intracerebral complement activation after traumatic brain injury remains unclear. In this study, the authors demonstrate that transgenic mice with astrocyte-targeted expression of the soluble complement inhibitor sCrry have a significantly reduced neurologic impairment and improved blood–brain barrier function after closed head injury compared with wild-type C57BL/6 littermates. This work further implicates the complement system as a participant in secondary progression of brain damage after head trauma and provides a strong rationale for future studies of posttraumatic pharmacologic complement inhibition.

scholarly journals Modulation of Host Immune Responses by the Cytolethal Distending Toxin of Helicobacter hepaticus

2006 ◽  
Vol 74 (8) ◽  
pp. 4496-4504 ◽  
Author(s):  
Jason S. Pratt ◽  
Kacey L. Sachen ◽  
Heather D. Wood ◽  
Kathryn A. Eaton ◽  
Vincent B. Young
Keyword(s):  
Immune Responses ◽  
Interleukin 10 ◽  
Cytolethal Distending Toxin ◽  
Helicobacter Hepaticus ◽  
Deficient Mutant ◽  
Wild Type ◽  
Host Immune Responses ◽  
Time Point

ABSTRACT Persistent murine infection with Helicobacter hepaticus leads to chronic gastrointestinal inflammation and neoplasia in susceptible strains. To determine the role of the virulence factor cytolethal distending toxin (CDT) in the pathogenesis of this organism, interleukin-10-deficient (IL-10−/−) mice were experimentally infected with wild-type H. hepaticus and a CDT-deficient isogenic mutant. Both wild-type H. hepaticus and the CDT-deficient mutant successfully colonized IL-10−/− mice, and they reached similar tissue levels by 6 weeks after infection. Only animals infected with wild-type type H. hepaticus developed significant typhlocolitis. However, by 4 months after infection, the CDT-deficient mutant was no longer detectable in IL-10−/− mice, whereas wild-type H. hepaticus persisted for the 8-month duration of the experiment. Animals infected with wild-type H. hepaticus exhibited severe typhlocolitis at 8 months after infection, while animals originally challenged with the CDT-deficient mutant had minimal cecal inflammation at this time point. In follow-up experiments, animals that cleared infection with the CDT-deficient mutant were protected from rechallenge with either mutant or wild-type H. hepaticus. Animals infected with wild-type H. hepaticus developed serum immunoglobulin G1 (IgG1) and IgG2c responses against H. hepaticus, while animals challenged with the CDT-deficient mutant developed significantly lower IgG2c responses and failed to mount IgG1 responses against H. hepaticus. These results suggest that CDT plays a key immunomodulatory role that allows persistence of H. hepaticus and that in IL-10−/− mice this alteration of the host immune response results in the development of colitis.

scholarly journals RAISED LEVEL OF LIPOPROTEIDE(A) AS A PREDICTOR OF CARDIOVASCULAR COMPLICATION POST REVASCULARIZATION OF THE LOWER ExTREMETIES ARTERIES

2018 ◽  
pp. 7-12
Author(s):  
N. A. Tmojan ◽  
О I. Afanasieva ◽  
A. Е. Zotikov ◽  
E. A. Klesareva ◽  
M. M. Abdulgamidov ◽  
...  
Keyword(s):  
Independent Predictor ◽  
Lower Extremities ◽  
Cardiovascular Death ◽  
Cardiovascular Complications ◽  
Lower Limbs ◽  
Repeat Revascularization ◽  
Extremity Amputation ◽  
Fatal Myocardial Infarction

Aim. Lipoproteide (a) (Lpa) is a pathogenetic risk factor of cardiovascular atherosclerotic disease. On the role of Lpa in the development of cardiovascular complications (CVC) after lower limbs arteries revascularization, there is lack of data. The aim of the study was assessment of Lpa relation to CVC occurrence after revascularization of lower extremities during 1 year follow-up.Material and methods. In the study, 111 patients were included (97 males, 14 females, mean age 66±9 y.o.), who had undergone revascularization of lower libms arteries due to atherosclerosis. As CVC during 1 year follow-up, the following were taken: recurrent intermittent claudication, lower extremity amputation, ischemic stroke, transient cerebral ischemia, non-fatal myocardial infarction, unstable angina, repeat revascularization and cardiovascular death. In all patients, in the blood serum, there were measured lipids and Lpa.Results. Within 1 year after revascularization there were 45 (41%) CVC. In the group with raised Lpa ≥30 mg/dL there were more CVC than in Lpa <30 mg/dL: relative risk 2,1 (95% CI 1,3-3,5; p=0,004). Hence the increased level of Lpa is an independent predictor of CVC after revascularization of lower extremities arteries.Conclusion. In prospective study, during 1 year after revascularization the level of Lpa ≥30 mg/dL is associated with double increase of the risk of CVC.

scholarly journals Succinate Dehydrogenase–Deficient Gastrointestinal Stromal Tumors

2019 ◽  
Vol 144 (5) ◽  
pp. 655-660 ◽  
Author(s):  
Ahmad Ibrahim ◽  
Shefali Chopra
Keyword(s):  
Succinate Dehydrogenase ◽  
Screening Method ◽  
Growth Factor Receptor ◽  
Wild Type ◽  
Children And Young Adults ◽  
The Common ◽  
Subunit B ◽  
Single Subunit

Succinate dehydrogenase (SDH)–deficient gastrointestinal stromal tumor (GIST) is a subset of wild-type GIST that constitutes approximately 10% of gastric GISTs. SDH-mutated GISTs lack mutations in the proto-oncogene receptor tyrosine kinase (also known as KIT, c-KIT, or CD117) or platelet-derived growth factor receptor α (PDGFR-α). These tumors have female predilection, affect children and young adults, and have a spectrum of behavior from indolent to progressive. These tumors have characteristic morphologic features including multinodular architecture, multiple tumors, lymphovascular involvement, and occasional lymph node metastasis. They can be seen in patients with Carney triad or Carney-Stratakis syndrome. Although a mutation in any one of the SDH subunits can be pathogenic, deficiency of a single subunit leads to loss of detectable SDH subunit B by immunohistochemistry, enabling a convenient, tissue-based screening method. The prognosis and the clinical course of these tumors is different from that of KIT- or PDGFR-α–mutated GISTs. Surgical management is considered the main line of treatment. SDH-mutated GISTs do not respond well to the common targeted therapy, with no objective tumor response to imatinib. The role of the pathologist in diagnosing these cases is imperative in management and subsequent follow-up.

Reasons for Electronic Nicotine Delivery System use and smoking abstinence at 6 months: a descriptive study of callers to employer and health plan-sponsored quitlines

2016 ◽  
Vol 26 (2) ◽  
pp. 126-134 ◽  
Author(s):  
K A Vickerman ◽  
G L Schauer ◽  
A M Malarcher ◽  
L Zhang ◽  
P Mowery ◽  
...  
Keyword(s):  
Health Plan ◽  
Response Rate ◽  
Smoking Abstinence ◽  
Future Studies ◽  
Quit Smoking ◽  
Survey Response Rate ◽  
Nicotine Delivery ◽  
System Use

ObjectiveDescribe cigarette smoking abstinence among employer and health plan-sponsored quitline registrants who were not using Electronic Nicotine Delivery Systems (ENDS), were using ENDS to quit smoking or were using ENDS for other reasons at the time of quitline registration.MethodsWe examined 6029 quitline callers aged ≥18 years who smoked cigarettes at registration, and completed ≥1 counselling calls, baseline ENDS use questions and a 6-month follow-up survey (response rate: 52.4%). 30-day point prevalence smoking quit rates (PPQRs) were assessed at 6-month follow-up (ENDS-only users were considered quit). Data were weighted for non-response bias. Logistic regression analyses controlled for participant characteristics and programme engagement.ResultsAt registration, 13.8% of respondents used ENDS (7.9% to quit smoking, 5.9% for other reasons). 30-day PPQRs were: 55.1% for callers using ENDS to quit, 43.1% for callers using ENDS for other reasons, and 50.8% for callers not using ENDS at registration. Callers using ENDS for other reasons were less likely to quit than other groups (adjusted ORs=0.65–0.77); quit rates did not significantly differ between non-ENDS users and those using ENDS to quit. Among callers using ENDS to quit at baseline, 40% used ENDS regularly at follow-up.ConclusionsENDS users not using ENDS to quit smoking were less successful at quitting at 6-month follow-up compared with callers using ENDS to quit smoking and callers who did not use ENDS at programme registration. Incorporating reasons for ENDS use may be important for future studies examining the role of ENDS in tobacco cessation.

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