Maria Antonietta Isgrò

Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects

Neuron-specific enolase (NSE) is known to be a cell specific isoenzyme of the glycolytic enzyme enolase. In vertebrate organisms three isozymes of enolase, expressed by different genes, are present: enolase α is ubiquitous; enolase β is muscle-specific and enolase γ is neuron-specific. The expression of NSE, which occurs as γγ- and αγ-dimer, is a late event in neural differentiation, thus making it a useful index of neural maturation.NSE is a highly specific marker for neurons and peripheral neuroendocrine cells. As a result of the findings of NSE in specific tissues under normal conditions, increased body fluids levels of NSE may occur with malignant proliferation and thus can be of value in diagnosis, staging and treatment of related neuroendocrine tumours (NETs).NSE is currently the most reliable tumour marker in diagnosis, prognosis and follow-up of small cell lung cancer (SCLC), even though increased levels of NSE have been reported also in non-small cell lung cancer (NSCLC). The level of NSE correlates with tumour burden, number of metastatic sites and response to treatment.NSE can be also useful at diagnosis of NETs and gastroenteropancreatic (GEP)-NETs.Raised serum levels of NSE have been found in all stages of neuroblastoma, although the incidence of increased concentration is greater in widespread and metastatic disease. Moreover, NSE determination in cord blood offers an early postnatal possibility of confirming the diagnosis of neuroblastoma in newborns.NSE has been demonstrated to provide quantitative measures of brain damage and/or to improve the diagnosis and the outcome evaluation in ischaemic stroke, intracerebral hemorrhage, seizures, comatose patients after cardiopulmonary resuscitation for cardiac arrest and traumatic brain injury.Increased NSE serum levels have also been found associated with melanoma, seminoma, renal cell carcinoma, Merkel cell tumour, carcinoid tumours, dysgerminomas and immature teratomas, malignant phaechromocytoma, Guillain-Barré syndrome and Creutzfeldt-Jakob disease.

The role of fluorine-18-fluorodeoxyglucose positron emission tomography in evaluating the response to tyrosine-kinase inhibitors in patients with metastatic primary renal cell carcinoma

Abstract Background. Positron emission tomography-computed tomography (PET-CT) using fluorodeoxyglucose (FDG) is increasingly used in the evaluation of patients with advanced renal cell carcinoma (RCC), primarily for staging purposes. The aim of this paper is to perform a systematic review about the usefulness of PET-CT using FDG in response assessment after treatment with tyrosine-kinase inhibitors (TKIs) in patients with advanced RCC. Materials and methods. The scientific literature about the role of PET-CT using FDG in the assessment of response to treatment with TKIs in patients affected by advanced RCC was systematically reviewed. Results. Seven studies about the role of PET-CT using FDG in the response assessment after treatment with TKIs (essentially sunitinib and sorafenib) in advanced RCC were retrieved in full-text and analysed, to determine the predictive role of this morpho-functional imaging method on patient outcome. Conclusions. To date, the role of PET-CT using FDG in evaluating the response to TKIs in metastatic RCC patients is still not well defined, partly due to heterogeneity of available studies; however, PET-CT reveals potential role for the selection of patients undergoing therapy with TKIs. The use of contrast-enhanced PET-CT appears to be promising for a “multi-dimensional” evaluation of treatment response in these patients.

Is fluorine-18-fluorodeoxyglucose positron emission tomography useful in monitoring the response to treatment in patients with multiple myeloma?

Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful diagnostic tool for the staging of patients with multiple myeloma (MM). The aim of this study is to perform a systematic review of the usefulness of FDG-PET or PET/CT in monitoring response to treatment in patients with MM. A comprehensive computer literature search of the PubMed/MEDLINE, Scopus and Embase databases was carried out to identify relevant peer-reviewed articles on the use of FDG-PET or PET/CT in monitoring the response to treatment in patients with MM. Ten studies described investigations of the role of FDG-PET or PET/CT in monitoring the response to treatment in 690 patients with MM or solitary plasmacytoma: six of these were conducted prospectively, while four studies were retrospective. These articles were retrieved in full-text version and analyzed. Based on these findings from the literature, FDG-PET or PET/CT appear to be useful in the assessment of treatment response in patients with MM.

The Role of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Evaluating the Response to Treatment in Patients with Multiple Myeloma

Background and Aim. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is well recognized as a powerful diagnostic tool in the initial staging of patients with multiple myeloma (MM). The aim of this paper is to perform a systematic review about the usefulness of FDG-PET or PET/CT in evaluating the response to treatment in patients with MM. Methods. The scientific literature about the role of FDG-PET or PET/CT in evaluating the response to treatment in patients affected by MM was systematically reviewed. Results. Ten studies about the role of FDG-PET or PET/CT in evaluating treatment response in MM were retrieved and discussed. Conclusions. FDG-PET or PET/CT seems to be helpful in assessing the response to treatment in patients with MM and in the evaluation of possible sites of recurrent or progressive disease.

Positive end-expiratory pressure during laparoscopy: cardiac and respiratory effects☆☆☆

STUDY OBJECTIVE To determine the effect of positive end-expiratory pressure (PEEP) on the respiratory system and on cardiac function. DESIGN Prospective randomized study. SETTING Operating room. PATIENTS 60 ASA physical status 1 women scheduled for pelvic laparoscopic surgery. INTERVENTIONS Patients were ventilated normally during surgery; PEEP was modified depending on patient group allocation. Group A was the control group and did not receive PEEP. Group B received PEEP 5 cmH2O and Group C received PEEP 10 cmH2O. MEASUREMENTS Respiratory parameters measured were partial pressure of arterial oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), and end-tidal carbon dioxide tension (ETCO2). Cardiac parameters measured were left ventricular end-diastolic volume index (LVEDVI), ie, ratio of LVEDV/body surface area (BSA; [LVEDVI = end-diastolic volume [EDV]/BSA); left ventricular (LV) systolic function, tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) fractional area change (FAC), RV dimensions in the apical 4-chamber view, tracing basal and mid-cavity minor dimensions and longitudinal dimension, cardiac index, systolic pulmonary artery pressure (PASP), and systolic RV pressure (RVSP). Respiratory and cardiac measurements were recorded at T0 (baseline); T1 (after anesthesia induction, before pneumoperitoneum induction); at 10 (T2), 20 (T3), and 30 (T4) minutes after CO2 insufflation; and at the end of surgery (T5). MAIN RESULTS Ventilation with PEEP at 10 cm H2O led to significant improvement in both respiratory and cardiac parameters. A reduction in pulmonary vascular resistance and enhanced washout of expiratory CO2 occurred. Ten and, to a lesser extent, 5 cm H2O of PEEP decreased LV stroke work. CONCLUSIONS Ventilation with PEEP (up to 10 cm H2O) recruits the hypoventilated areas of the lungs and reduces cardiac afterload.

The epithelial–mesenchymal transition in cancer: a potential critical topic for translational proteomic research

The epithelial–mesenchymal transition (EMT) is a morphogenetic process that results in a loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. First described in embryogenesis, the EMT has been recently implicated in carcinogenesis and tumor progression. In addition, recent evidence has shown that stem-like cancer cells present the hallmarks of the EMT. Some of the molecular mechanisms related to the interrelationships between cancer pathophysiology and the EMT are well-defined. Nevertheless, the precise molecular mechanism by which epithelial cancer cells acquire the mesenchymal phenotype remains largely unknown. This review focuses on various proteomic strategies with the goal of better understanding the physiological and pathological mechanisms of the EMT process.

The Role of Fluorine-18-fluorodeoxyglucose Positron Emission Tomography in Assessing the Response to Neoadjuvant Treatment in Patients with Osteosarcoma

Aim. The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with fluorine-18-fluorodeoxyglucose (FDG) in assessing the response to neoadjuvant treatment in patients with osteosarcoma (OS). Methods. A comprehensive literature search of published studies through March 2012 in PubMed/MEDLINE, Embase, and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed. Results. Twenty-two studies have investigated the role of FDG-PET and FDG-PET/CT in the evaluation of response to neoadjuvant treatment with either chemotherapy or radiation therapy in patients with OS. The main findings of these studies are presented. Conclusion. FDG-PET or PET/CT seems to be sensitive and reliable diagnostic tools in the assessment of metabolic response to treatment in patients with OS, after baseline PET evaluation has been performed in advance. However, false positive findings due to inflammation in sites of tumoral response should be considered.

NT-proBNP: A marker of preclinical cardiac damage in arterial hypertension.

BACKGROUND The cardiac left ventricle responds to pressure overloads with mechanisms culminating in irreversible structural/functional cardiac alterations (left ventricular hypertrophy and/or diastolic dysfunction), inducing myocardial cells to secrete natriuretic peptides (NT-proBNP) antagonists of the renin-angiotensin-aldosterone system. The aim of this study was to evaluate the diagnostic accuracy of serum NT-proBNP levels in order to detect structural/functional cardiac diseases assessed by echocardiography. METHODS A total of 126 consecutive newly diagnosed, never before treated, hypertensive patients (30-67 years) were enrolled, and clinical, echocardiography parameters and biochemical data were collected. Our reference was the presence of structural/functional cardiac disease (CSFD) and our index text was the serum NT-proBNP levels. RESULTS NT-proBNP levels in CSFD patients were ~2 times higher than in non-CSFD subjects (median 61 vs 29 ng/L, n=50 and 76, respectively); in addition, 60% of CSFD subjects (only 14% of which with pathological levels, >125 ng/L), and 30% without CSFD showed NT-proBNP concentrations higher than 50 ng/L. However, ROC curves demonstrated a low specificity (38%) (calculated at 90% sensitivity at a cut-off of 22.5 ng/L). DISCUSSION NT-proBNP levels, as a screening tool for cardiac structural/functional disease, appear to be limited, because of the low specificity. However, the strong association between its concentration and the establishment of irreversible cardiac hypertrophy prompts successive studies aimed to ascertain the use of its serum levels as an early alert indicator of disease severity.

Enhanced liver fibrosis test as a reliable tool for assessing fibrosis in nonalcoholic fatty liver disease in a clinical setting

Background Liver fibrosis is the main determinant and predictor of the clinical course of nonalcoholic fatty liver disease (NAFLD). To date, a liver biopsy is still considered the gold standard for staging fibrosis. The aim of this study was to investigate the diagnostic accuracy of the commercial enhanced liver fibrosis (ELF) test manufacturers cutoff value (≥9.8) in identifying severe fibrosis for adult patients with histologically confirmed NAFLD. Methods We tested the ELF test in a clinical practice, prospective cohort of 82 consecutive patients who consecutively underwent percutaneous liver biopsy. Results All stages of liver fibrosis were represented in our cohort, and severe fibrosis was present in 15 of 82 patients (18.3%). The stage of fibrosis was significantly associated with ELF score (Spearmans rho = 0.483, p<0.001). The commercial ELF test manufacturers cutoff identified severe fibrosis with good sensitivity (86.7%; 95% confidence interval [95% CI], 0.69-1.04) and high specificity (92.5%; 95% CI, 0.86-0.99), with a positive predictive value of 72% and negative predictive value of 97%. Conclusions Our data could support the use of the ELF test in clinical practice.

Quali-quantitative differences of adipose tissuederived stromal cells from superficial and deep subcutaneous lipoaspirates: a matter of fat

Subcutaneous fat (or hypoderm) represents a valuable reservoir of adiposederived stem cells (ASCs), residing in the stromal vascular fraction (SVF), widely exploited in regenerative medicine applications, being easily harvested through lipoaspiration. The lack for standardized procedures for autologous fat grafting, guided research efforts aimed at identifying possible differences related to the harvesting site, that may affect cell isolation yield, cell growth properties and clinical outcomes. The hypoderm features a complex architecture: the superficial fascia separates the superficial adipose tissue (SAT) from the deep layer (DAT). Aim of this study was to unravel the differences between SAT and DAT, considering morphological structure, SVF composition and ASCs’ properties. SAT and DAT specimens were collected from three distinct anatomical regions (abdomen, thigh and knee) of female individuals and comparatively analyzed through histology, flow citometry, and qPCR. ASCs were isolated in primary culture and used for in vitro differentiation assays. Our results indicated that liposucted SAT contains a higher stromal tissue compound, along with a higher proportion of CD105-positive cells, compared to DAT from the same anatomical region. Also, cells isolated from SAT displayed increased multipotency and stemness features. All differences were mainly evidenced in specimens harvested from the abdominal region. According to our results, SAT features overall increased stem properties. Given that subcutaneous adipose tissue is currently exploited as the gold standard source for high yield isolation of somatic stem cells, these results may provide precious hints toward defining a prioritization of tissue harvesting site for regenerative medicine applications.