Prognostic Value Of Different Types Research Articles

Predictive value of myocardial contrast echocardiography in evaluating myocardial perfusion and prognosis after percutaneous coronary intervention in patients with acute myocardial infarction

Objective: To evaluate myocardial microcirculation perfusion with myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction after percutaneous coronary intervention (PCI), and to explore the prognostic value of different types of myocardial microcirculation perfusion. Methods: This is a prospective cohort study. Patients with acute myocardial infarction who underwent successful PCI in Nanfang Hospital of Southern Medical University and Kanghua Hospital of Dongguan City from October 2019 to June 2021 were selected. All the enrolled patients completed MCE examination within 72 hours after PCI. According to the examination results, the patients were divided into normal microcirculation perfusion group, delayed microcirculation perfusion group, and blocked microcirculation perfusion group. Adverse cardiovascular events including all-cause death, cardiovascular death, and angina re-hospitalization were followed up, and left ventricular ejection fraction (LVEF) review results were collected at six months to one year after surgery. Kaplan-Meier survival curve was used to investigate the difference in the incidence of adverse cardiovascular events in different myocardial perfusion groups, and Cox regression analysis was used to evaluate the effect of myocardial perfusion on adverse cardiovascular events. Results: A total of 113 patients with acute myocardial infarction were included, aged (56.3±11.5) years, with 88(78%) males. There were 31 cases in the normal microcirculation perfusion group, 43 cases in the delayed microcirculation perfusion group and 39 cases in the blocked microcirculation perfusion group. LVEF was reviewed in 49 patients, and LVEF in the delayed microcirculation perfusion group was significantly improved compared with baseline at follow-up ((63.3±1.2) % vs. (58.6±1.8) %, P=0.043), and there was no statistically significant difference between the other two groups (all P>0.05). The median follow-up time was 473 days, during follow-up period 30 adverse cardiovascular events occurred. Kaplan-Meier survival curve analysis showed that there was a statistically significant difference in the incidence of adverse cardiovascular events among the three groups (Plog-rank=0.029). Cox regression analysis showed that abnormal microcirculation perfusion (defined as delayed and blocked microcirculation perfusion) was an independent predictor of adverse cardiovascular events in patients with acute myocardial infarction after PCI (HR=1.90, 95%CI1.16-3.12, P=0.011). Conclusions: Microcirculatory perfusion decrease or lost is common in patients with acute myocardial infarction after PCI. Timely restoration of blood flow reconstruction can save heart function when microcirculatory perfusion decreases. Microcirculatory perfusion is a predictor of adverse cardiovascular events in patients with acute myocardial infarction, and patients with poor myocardial perfusion are more likely to experience adverse cardiovascular events.

AML-282: Prognostic Values of D816V KIT Mutation and Peri-Transplant CBFB-MYH11 MRD Monitoring on Acute Myeloid Leukemia with CBFB-MYH11

<h3>Context:</h3> Controversies exist in the prognostic value of KIT mutations and the optimal thresholds and time points for measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with CBFB-MYH11. <h3>Objective:</h3> This study aimed to evaluate the prognostic value of different types of KIT mutations and CBFB-MYH11 quantification in AML patients with CBFB-MYH11 who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) or autologous HSCT (auto-HSCT) and the clinical relevance of each transplant strategy in each risk group. <h3>Design:</h3> We retrospectively evaluated 88 patients who underwent allo-HSCT (n=60) or auto-HSCT (n=28). <h3>Setting:</h3> A referral center. <h3>Patients:</h3> Ninety-six consecutive AML patients with CBFB-MYH11 in remission who underwent HSCT at the Catholic Hematology Hospital between 2009 and 2019. After excluding two patients who underwent second HSCT and four patients without data for KIT mutations or pre-transplant CBFB-MYH11 MRD data, 88 patients were finally included in this study. <h3>Interventions:</h3> Not applicable. <h3>Main Outcome Measures:</h3> We retrospectively compared survival outcomes according to different types of KIT mutations and CBFB-MYH11 MRD levels. <h3>Results:</h3> The D816V KIT mutation was significantly associated with post-transplant relapse, contrasting with other types of mutations in KIT. Pre- and post-transplant (3 months after transplant) CBFB-MYH11 MRD assessments were useful for predicting post-transplant relapse and poor survival. The optimal threshold was determined as a 2-log reduction at both time points. In multivariate analysis, the D816V KIT mutation and CBFB-MYH11 MRD assessments were independently associated with post-transplant relapse and survival. Stratification by D816V KIT and pre-transplant CBFB-MYH11 MRD status further distinguished the risk of relapse and survival. Auto-HSCT was superior to allo-HSCT in MRD-negative patients without D816V KIT, while allo-HSCT trended to be superior to auto-HSCT in patients with MRD positivity or the D816V KIT mutation. <h3>Conclusions:</h3> This study demonstrated the differentiated prognostic value of the D816V KIT mutation in AML with CBFB-MYH11 and clarified the optimal time points and thresholds for CBFB-MYH11 MRD monitoring in the setting of HSCT.

Assessment of a standardized EEG reactivity protocol after cardiac arrest

ObjectiveReactivity assessment during EEG might provide important prognostic information in post-anoxic coma. It is still unclear how best to perform reactivity testing and how it might be affected by hypothermia. Our primary aim was to determine and compare the effectiveness, inter-rater reliability and prognostic value of different types of stimulus for EEG reactivity testing, using a standardized stimulation protocol and standardized definitions. Our secondary aims were to assess the effect of hypothermia on these measures, and to determine the prognostic value of a simplified sequence with the three most efficient stimuli. MethodsProspective single-center cohort of post-anoxic comatose patients admitted to the intensive care unit of an academic medical center between January 1, 2016 and December 31, 2018 and receiving continuous EEG monitoring (CEEG). Reactivity was assessed using standardized definitions and standardized sequence of stimuli: auditory (mild noise and loud noise), tactile (shaking), nociceptive (nostril tickling, trapezius muscle squeezing, endotracheal tube suctioning), and visual (passive eye opening). Gwet’s AC1 and percent agreement (PA) were used to measure inter-rater agreement (IRA). Ability to predict favorable neurological outcome (defined as a Cerebral Performance Category of 1 to 2: no disability to moderate disability) was measured with sensitivity (Se), specificity (Sp), accuracy, and odds ratio [OR]. These were calculated for each stimulus type and at the level of the entire sequence comprising all the stimuli. ResultsOne-hundred and fifteen patients were included and 242 EEG epochs were analyzed. Loud noise, shaking and trapezius muscle squeezing most frequently elicited EEG reactivity (42%, 38% and 38%, respectively) but were all inferior to the entire sequence, which elicited reactivity in 58% cases. The IRA for reactivity to individual stimuli varied from moderate to good (AC1:58–69%; PA:56–68%) and was the highest for loud noise (AC1:69%; PA:68%), trapezius muscle squeezing (AC1:67%; PA:65%) and passive eye opening (AC1:68%; PA:64%). Mild (odds ratio [OR]:11.0; Se:70% and Sp:86%) and loud noises (OR:27.0; Se:73% and Sp:75%), and trapezius muscle squeezing (OR:15.3; Se:76% and Sp:83%) during hypothermia had the best predictive value for favorable neurological outcome, although each was inferior to the whole sequence (OR:60.2; Se:91% and Sp:73%). A simplified sequence of loud noise, shaking and trapezius muscle squeezing had the same performance for predicting neurological outcome as the entire sequence. Hypothermia did not significantly affect the effectiveness of stimulation, but IRA was slightly better during hypothermia, for all stimuli. Similarly, the predictive value was higher during hypothermia than during normothermia. ConclusionsDespite a standardized stimulation protocol and standardized definitions, the IRA of EEG reactivity testing in post-anoxic comatose patients was only good at best (AC1 < 70%), and its predictive value for neurological outcome remained imperfect, in particular with Sp values < 90%. While no single stimulus appeared superior to others, a full sequence using all stimuli or a simplified sequence comprising loud noise, shaking and trapezius muscle squeezing had the best combination of IRA and predictive value. SignificanceThis study stresses the necessity to use multiple stimulus types to improve the predictive value of reactivity testing in post-anoxic coma and confirms that it is not affected by hypothermia.

Management of Non-Colorectal Digestive Cancers with Microsatellite Instability.

Simple SummaryMicrosatellite instability (MSI) is an established predictive biomarker for immune checkpoint inhibitors with potential prognostic value in different types of tumors. Its prevalence and clinical utility vary in gastrointestinal cancers. In this review, we will discuss the role of MSI status in the management of non-colorectal cancers of the digestive system and address ongoing research work and mechanistic rationale(s) for future studies in this field.Microsatellite instability (MSI) is a hallmark of genetic predisposition to DNA damage. It arises from either germline or somatic events leading to impaired function of the mismatch repair system. It can be detected via genetic sequencing or immunohistochemistry with relatively high concordance rates. The presence of MSI in a tumor reflects a high neoantigen load and predicts favorable treatment response to immune checkpoint inhibitors (ICIs). In gastrointestinal cancers, MSI is a predictive biomarker for ICIs with potential prognostic impact but its clinical utility varies widely depending on tumor type. This may be explained by the complexity of tumor microenvironment as highlighted by recent translational studies. In this review, we will discuss the predictive and prognostic value of MSI status in non-colorectal cancers of the digestive system, important clinical trials involving ICIs and potential strategies to overcome resistance to immunotherapy.

Morphological Characteristics and Clinical Significance of Different Types of Tumor Vessels in Patients with Stages I-IIA of Squamous Cervical Cancer.

The determination of factors associated with progression of cervical cancer is important, both for a recurrence risk assessment and for determining optimal treatment tactics. Previously, we showed the prognostic value of different types of tumor microvessels (MVs) in gastric and breast cancer. The object of this research was to study the morphology and clinical significance of different tumor microvessels in early cervical cancer. A total of 65 archived paraffin blocks of patients with I-IIA stages of squamous cervical cancer were investigated. Samples were stained with Mayer hematoxylin and immunohistochemically using antibodies to CD34, podoplanin, HIF-1a, and Snail. The eight types of tumor MVs differed in morphology were identified. It was established that only the dilated capillaries (DСs) with weak expression of CD34, the contact type DCs, the capillaries in tumor solid component, and the lymphatic vessels in the lymphoid and polymorphic cell infiltrates of tumor stroma are associated with clinical and pathological characteristics of early cervical cancer. Preliminary results also suggest that a combination of fragmentation in tumor solid component and the contact type DCs may predict a recurrence of early cervical cancer. Given the small number of cervical cancer recurrences, the predictive significance of the described markers requires a more thorough examination.

Tumor-associated macrophage infiltration and prognosis in colorectal cancer: systematic review and meta-analysis.

Tumor-associated macrophages (TAMs) are key components of colorectal cancer (CRC) microenvironment, but their role in CRC prognosis is not fully defined. This study aimed to evaluate prognostic value of different types and distribution of TAMs in CRC. Total 27 studies with 6115 patients were searched from PubMed and Embase and analyzed to determine the association between TAMs, including distinct TAM subsets and infiltration location, and CRC survival. The prognostic impact of TAMs on CRC was further stratified by tumor type and mismatch repair system (MMR) status. A pooled analysis indicated that high density of TAMs in CRC tissue was significantly associated with favorable 5-year overall survival (OS) but not with disease-free survival (DFS). CD 68+ TAM subset correlated with better 5-year OS, while neither CD68+NOS2+ M1 subset nor CD163+ M2 subset was correlated with 5-year OS. Increased CD68+ TAM infiltration in tumor stroma but not in tumor islet predicted improved 5-year OS. Stratification by tumor type and MMR status showed that in colon cancer or MMR-proficient CRC, elevated TAM density was associated with better 5-year OS. High infiltration of CD68+ TAMs could be a favorable prognostic marker in CRC. Future therapies stimulating CD68+ TAM infiltration may be promising in CRC treatment.

CLINICAL AND PROGNOSTIC VALUE OF HYPONATREMIA IN PATIENTS WITH CHRONIC HEART FAILURE

The aim : to assess the short-term prognostic value of different types of hyponatremia in patients hospitalized for acute decompensated chronic heart failure. Material and methods. A prospective study included 396 patients hospitalized for acute decompensated chronic heart failure. Hyponatremia was diagnosed in cases of serum sodium level less than 135 mmol/l. The pre-hospital hyponatremia was defined as a decreased serum sodium level on admission, whereas the hospital hyponatremia was referred to cases occurred during hospitalization. In patients with pre-hospital hyponatremia drop of sodium levels ≥ 3 mmol/l during hospitalization was defined as a progressive hyponatraemia. The influence of different types of hyponatremia on the hospital prognosis was determined, while the composite primary endpoint was all-cause mortality and/or transfer to the intensive care unit. Results. Patients with hyponatremia were older and had more severe clinical signs of chronic heart failure, lower left ventricle ejection fraction and higher diastolic dysfunction than normonatremic patients. After adjustment for age, comorbidity and severity of chronic heart failure in Cox regression models hyponatremia was an independent predictor of all-cause mortality and transfer to the intensive care unit (odds ratio 3.1; p &lt; 0.05). Pre-hospital hyponatremia had a higher prognostic value on outcome compared with hospital hyponartemia (odds ratio 3.9 versus 2.9, respectively; p &lt; 0.05). Progressive hyponatremia was associated with a marked increase of mortality and transfer to the intensive care unit (odds ratio 6.8; p &lt; 0.05). Conclusion. Pre-hospital and hospital hyponatremia are independent predictors for short-term outcomes in patients hospitalized for acute decompensated chronic heart failure. Progression of the pre-hospital hyponatremia is associated with significantly increase of all-cause mortality and risk of transfer to the intensive care unit.

Prognostic value of various subtypes of extracellular DNA in ovarian cancer patients

BackgroundPatients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy. Plasma DNA has been shown to have a prognostic value in different types of cancer including ovarian carcinoma. Whether total circulating DNA, which can be assessed much easier without knowing the tumor-specific mutations, has similar informative value is currently unknown. The aim of this study was to evaluate the prognostic value of extracellular DNA in advanced ovarian cancer.MethodsThis prospective study included 67 patients (pts) with ovarian cancer treated with 1st line paclitaxel and carboplatin (25 pts) and paclitaxel, carboplatin and bevacizumab (42 pts). Thirty-five patients had optimal surgical debulking before chemotherapy. Extracellular DNA was quantified using real time PCR before administration of chemotherapy (67 pts) and after 6 cycles of chemotherapy (44 pts).ResultsTotal extracellular DNA (ecDNA), as well as extracellular DNA of nuclear (nDNA) and mitochondrial origin (mtDNA) significantly (p < 0.05) decreased after 6 cycles of chemotherapy (by 54%, 63% and 52%, respectively. Patients with stage I disease had significantly lower mtDNA compared to patients with stage II-IV (8604 vs. 16, 984 ge/mL, p = 0.03). Patients with lower baseline nDNA had superior progression-free (HR = 0.35 (0.14–0.86)) and overall survival (HR = 0.18 (0.04–0.77). The prognostic value of nDNA was confirmed independent of tumor stage and confirmed in multivariate analysis.ConclusionsOur data suggest that ecDNA of both, nuclear and mitochondrial origin could be added to prognostic markers in ovarian cancer. Analysis of ecDNA does not require the knowledge of tumor-specific mutations in contrast to the quantification of tumor-derived ecDNA. Study of the dynamics and cell type-specific source of the ecDNA could shed light on its biology in cancer and might help to direct the treatment of ovarian cancer.

Abstract 2649: Expression and prognostic value of EGR1 and EGR3 in gliomas

Abstract Introduction Gliomas are the most frequent primary brain tumors. For the most malignant glioma - the glioblastoma - the median survival is below 15 months. Since only few prognostic biomarkers are of benefit in daily practice, new markers are urgently needed. EGR1 and EGR3 are transcription factors involved in the regulation of cell-cycle and cell differentiation, but they have also been associated with migration of cancer cells. Studies have shown prognostic potential of EGR1 and EGR3 in breast-, gastric-, colorectal-, and prostate cancer. The purpose of this study was to investigate the expression and potential prognostic value of EGR1 and EGR3 in gliomas. Methods Samples of 214 gliomas were stained with anti-EGR1 and -EGR3 antibodies respectively. The stainings were assessed with a software-based digital classifier and a semi-quantitative scoring system. Kaplan-Meier estimates and Log-rank tests were used to compare survival distributions, and ROC-curve analysis with dichotomizing was applied to identify optimal cut-off values. Cox proportional hazards regression was performed to further investigate and identify independent prognostic variables. Results Both EGR1 and EGR3 were expressed in all glioma samples, but with considerable variation between tumors. EGR1 expression ranged from 1-83% positive cells and increased with WHO grade, while EGR3 expression ranged from 5-95% positive cells independent of WHO grade. High EGR1 levels were associated with improved survival in glioblastomas, while low EGR3 levels were associated with improved survival in WHO grade II and III gliomas. In glioblastomas, the EGR1 high/EGR3 low group was associated with improved patient survival when compared to the EGR1 low/EGR3 high group. Similar results were found in MGMT-promoter methylated glioblastomas, but not in MGMT-unmethylated glioblastomas. Cox proportional hazards regression showed that a high EGR1 fraction remained a significant prognostic variable when adjusted for confounders, both in all gliomas as one group (P=0.048) and glioblastomas exclusively (P=0.011). The combination of EGR1 high/EGR3 low in glioblastomas also remained significant after adjustment for confounders (P=0.030). Conclusion Both EGR1 and EGR3 proteins were expressed in all investigated gliomas. High levels of EGR1 seemed to be associated with improved patient survival in glioblastomas. In MGMT-promoter methylated glioblastomas, the EGR1 high/EGR3 low group was associated with improved patient survival when compared to the EGR1 low/EGR3 high group. Validation of the results in an additional patient cohort is needed, including analysis of prognostic value in different types of grade II and III gliomas. Citation Format: Arnon M. Knudsen, Ida Eilertsen, Susanne Kielland, Henning B. Boldt, Caspar S. Mellegaard, Sune Munthe, Bjarne W. Kristensen. Expression and prognostic value of EGR1 and EGR3 in gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2649.

Prognostic value of various subtypes of circulating DNA in ovarian cancer patients.

e17092 Background: Patients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy. Circulating tumor DNA has been shown to have a prognostic value in different types of cancer including ovarian carcinoma. Whether total circulating DNA, which can be assessed much easier without knowing the tumor-specific mutations, has similar informative value is currently unknown. The aim of this study was to evaluate the prognostic value of circulating DNA in advanced ovarian cancer. Methods: This prospective study included 67 patients (pts) with ovarian cancer treated with 1st line paclitaxel and carboplatin (25 pts) and bevacizumab (42 pts). Thirty-five patients had optimal debulking before chemotherapy. Circulating plasma DNA was quantified using real time PCR before administration of chemotherapy (67 pts) and after 6 cycles of chemotherapy (44 pts). Results: Total extracellular DNA (ecDNA), as well as extracellular DNA of nuclear (nDNA) and mitochondrial origin (mtDNA) significantly (p &lt; 0.05) decreased after 6 cycles of chemotherapy (by 54%, 63% and 52%, respectively. Patients with stage I disease had significantly lower mtDNA compared to patients with stage II-IV (8604 vs. 16984 ge/mL, p = 0.03). Patients with lower baseline nDNA had superior progression-free (HR=0.35 (0.14-0.86)) and overall survival (HR=0.18 (0.04-0.77). The prognostic value of nDNA was confirmed independent of tumor stage and confirmed in multivariate analysis. Conclusions: Our data suggest that ecDNA of both, nuclear and mitochondrial origin, could be added to prognostic markers in ovarian cancer. This is of importance as this analysis does not require the knowledge of tumor-specific mutations in contrast to the quantification of tumor-derived ecDNA. Analysis of the dynamics and cell type-specific source of the ecDNA could shed light on its biology in cancer and might help to direct the treatment of ovarian cancer.

Lymphocyte to monocyte ratio is associated with response to first-line platinum-based chemotherapy and prognosis of early-stage non-small cell lung cancer patients.

Lymphocyte to monocyte ratio (LMR) has shown prognostic value in different types of cancer. This study assessed the prognostic performance of LMR in early-stage non-small cell lung cancer (NSCLC) patients and investigated the influence of LMR on the treatment response in patients receiving first-line platinum-based chemotherapy. Four hundred eighty-eight NSCLC patients and 500 healthy donors were enrolled in this study. The cutoff value for LMR was chosen by receiver operating characteristic curve analysis. The prognostic significance of markers was assessed by univariate and multivariate Cox regression models. The median overall survival was 43months, and the median progression-free survival was 38months. LMR was associated with disease status and the treatment response of first-line platinum-based chemotherapy. Multivariate analysis showed that LMR was an independent prognostic factor for both overall survival (hazard ratio = 1.53, 95% confidence interval = 1.09-2.14, P = 0.015) and progression-free survival (hazard ratio = 1.20, 95% confidence interval = 1.02-1.67, P = 0.028). Furthermore, integration of LMR into a prognostic model including TNM stage, tumor status, chemotherapy, and histological type generated a nomogram, which predicted accurately overall survival for NSCLC patients. Decreased LMR may be a potential biomarker of disease status, worse response to first-line platinum-based chemotherapy, and worse survival for NSCLC patients. A prospective study is warranted for further validation of our findings.

Association between inflammatory markers and prognosis in resected pancreatic cancer (PC).

250 Background: Inflammatory markers like the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) or fibrinogen (F) and nutritional markers like albumin (alb) have a prognostic value in different types of cancer. However, the paucity of data in pancreatic cancer (PC) keeps their role in this setting unclear. We aimed to determine whether NLR, PLR, F and alb may be prognostic factors in resectable PC. Methods: Demographic, histologic and serologic characteristics (pre and postoperative blood counts) of 77 consecutive PC patients (pts),who underwent curative surgery at our centre between January 2003 and December 2013,were retrospectively collected. We investigated the association of presurgical NLR, PLR, F and alb with overall survival (OS) and disease free survival (DFS) and analyzed the impact of their kinetics after surgery on the outcomes. Results: main pts characteristics are showed in Table. Median OS and DFS were 23 months (m), (95% CI 13.4-32.5) and 10 m (95% CI 7.4 - 12.6) respectively. Pts with NLR &lt; 5 had a significant improvement in OS compared to those with NLR &gt; 5 (29 m vs.16 m, log rank p &lt;0.05 ). F values &lt; 450 mg/dl were also associated with increased OS (30 vs. 16 m, log rank p=0.032). After adjusting by the Cox regression model, only NLR remained an independent prognostic factor for OS (HR, 1.6; p&lt;0.05). PLR (grouped in 3 cutoffs: &lt; 150, 150-300 and &gt;300) and alb (&lt;2, 2-3.5, &gt;3.5 mg/dl) were not associated with significant differences in outcomes. Pre and postoperative values were compared. No association was found between a drop on NLR to &lt;5 after surgery and OS or DFS. Conclusions: our results support that NLR could be a prognostic factor in PC pts undergoing surgery. Changes in NLR due to surgery do not seem to impact the outcome. PLR, F and alb did not correlate with prognosis. [Table: see text]

Neutrophil to lymphocyte ratio (NLR) as a predictive marker of response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in EGFR mutation-positive non-small cell lung cancer (NSCLC).

e19117 Background: NLR has prognostic value in different types of cancers including NSCLC. EGFR TKI’s have conferred survival benefit to patients (pts) with advanced NSCLC harboring EGFR TK mutations (EGFRm+), although response and duration of clinical benefit varies. The predictive value of NLR in this setting is unknown. Methods: We conducted a retrospective study on 42 pts with EGFR TKI-naive advanced EGFRm+ NSCLC. The objective of the study was to explore the correlation between NLR with response to EGFR TKI therapy. Pretreatment NLR was calculated from complete blood count (CBC) before the pts were started on Erlotinib and post treatment NLR was calculated from CBC after being on Erlotinib at the end of 2 months (mo) and 4 mo. Pts were classified into two groups, High NLR ≥ 5 or Low NLR < 5 . Response evaluation using RECIST 1.1 was based on imaging done at the end of 4 months of therapy. Fisher exact test was used for analysis. Results: The mean age of pts was 65y. Male: Female ratio was 1:2. 23 pts...

Specific Capture and Release of Circulating Tumor Cells Using Aptamer‐Modified Nanosubstrates

Circulating tumor cells (CTCs)[1] are cancer cells that have propagated from tumors, spreading into the bloodstream as the cellular origin of fatal metastasis. Besides conventional diagnostic approaches (e.g., tumor biopsy, anatomical/molecular imaging and serum marker detection), detecting CTCs in peripheral blood is of prognostic value in different types of solid tumors, especially for predicting patient survival. The fact is that CTC detection have been technically challenging because of the extremely low abundance (a few to hundreds per mL) of CTCs among a high number (109 cells mL-1) of hematologic cells.[2] Over the past decade, a diversity of diagnostic technologies has been demonstrated for CTC detection using different working mechanisms. The current FDA-cleared CellSearch™ Assay is based on immunomagnetic separation of CTCs. Due to its unsatisfactory efficiency and high cost, researchers have been exploiting new technologies,[3] e.g., flow cytometry, size-based filtration systems and microfluidic devices that may offer improved sensitivity and reduced cost for CTC detection. In addition to the prognostic utility of CTC-based diagnostics, it is conceivable that the molecular signatures and functional readouts derived from CTCs will shed much valuable insight into tumor biology during the critical window where therapeutic intervention could make a significant difference.

Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and patient survival in cervical adenocarcinoma

The incidence of cervical adenocarcinoma, which accounts for 10-20% of all cervical cancers, has increased continuously in developed countries during the last two decades, unlike squamous cell cervical carcinoma. This increasing trend, noted particularly among women under the age of 40 years, has occurred despite extensive cytological Pap smear screening. A deeper understanding of the etiology of cervical adenocarcinoma, better preventive measures and reliable prognostic markers are urgently needed. The human leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family includes: LRIG1, LRIG2 and LRIG3. LRIG expression has proven to be of prognostic value in different types of human cancers, including breast cancer, early stage invasive squamous cervical cancer, cutaneous squamous cell carcinoma, oligodendroglioma and astrocytoma. LRIG1 functions as a tumor suppressor, while less is known about the functions of LRIG2 and LRIG3. This study evaluated the expression of the three LRIG proteins in tumor specimens from 86 women with pure cervical adenocarcinoma by immunohistochemistry. Possible correlations between LRIG expression and known prognostic factors, including human papillomavirus (HPV) status, FIGO stage and histology were investigated. Patient survival data were collected retrospectively and the possible prognostic value of LRIG protein expression was investigated. High staining intensity of LRIG1 and high fraction of LRIG3-positive cells were significantly associated with patient survival, and positive correlations were found between LRIG1 and LRIG3 staining intensity and HPV status. Thus, the LRIG proteins may be important determinants of cervical adenocarcinoma progression and their diagnostic and prognostic potential should be studied further.

Circulating endothelial and endothelial progenitor cells in non-small-cell lung cancer

New treatments have recently been introduced for treating non-small-cell lung cancer. Chemotherapeutic agents, such as pemetrexed, and targeted therapies, such as bevacizumab, erlotinib or gefitinib, have extended treatment options for selected histological subgroups. Antiangiogenic treatments, either associated with conventional chemotherapeutic drugs or given alone as maintenance therapy, constitute an active clinical research field. However, not all lung cancer patients benefit from antiangiogenic compounds. Moreover, tumour response assessment is often difficult when using these drugs, since targeted therapies generally do not cause rapid and measurable tumour shrinkage but, rather, long stabilisations and slight density changes on imaging tests. The finding of clinical or biological factors that might identify patients who will better benefit from these treatments, as well as identifying surrogate markers of tumour response and prognosis, is an issue of great interest. In that sense, different research lines have investigated the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. Circulating endothelial (CECs) and endothelial progenitor cells (CEPCs) are of prognostic value in different types of cancers, and relevant data are published about their potential usefulness as predictors of response to chemotherapy and antiangiogenic treatments. In this review, we discuss the data available on the role of CECs and CEPCs as prognostic factors and as surrogate markers of treatment response in non-small-cell lung cancer.

The prognostic value of different types of tests in courses in educational psychology.

The prognostic value of different types of tests in courses in educational psychology.