Diagnostic criteria in invasive pituitary adenomas

Pituitary adenomas are benign pituitary primary tumors, the most frequent type of tumor in the pituitary fossa. An important part, around 1/3 of the pituitary adenomas manifests an aggressive behavior, growing faster and invading into parasellar areas (cavernous sinus, neural tissues and bones).Objectives: the first aim of this paper is to review the last findings about invasiveness diagnostic criteria, imagistic and biomarkers, which can be used in the classification of pituitary tumors and also to predict the probability of invasiveness, tumor recurrence and suspicion of malignancy. The second aim is to highlight the morphological and clinic types of invasive pituitary adenomas.Materials and methods: we performed a systematic review and analysis of the published articles, searching PubMed between January 1985 and December 2015. There were selected articles published in English, reviews and abstracts. During the advanced search type in PubMed, combinations of the following keywords were used: “pituitary adenoma”, “invasive”, “aggressive”, “biomarkers”, “classification”, “histological subtypes”, ‘”immunohistochemical markers”.Results: 215 articles were selected, regarding diagnostic, prognostic and therapeutic aspects. There were some histological subtypes of pituitary adenomas known as having an aggressive clinical behavior. Several biomarkers were identified as being associated with the invasive feature: proliferation markers (Ki-67 index, number of mitoses, p53 & p27 expression, microvascularization density, telomerase, topoisomerase 2 Alpha), matrix metalloproteinases, protein kinase C, cyclooxygenase-2, E-cadherin, transcription Factors, genetic alterations (PTTG gene, Galectin-3 protein/ LGALS3 gene), apoptosis markers. Based on their invasion and proliferation characteristics, pituitary tumors are proposed to be classified into five grades (1a, 1b, 2a, 2b, 3), the grade 2b tumor with high risk of recurrence being considered as tumor suspected of malignancy.Conclusions: Using a set of specific biological markers for invasive process, there is hope to establish an early diagnosis and prevention of invasive pituitary adenomas. Due to the fact that aggressive pituitary tumors are generally difficult to manage, unresponsive to therapy, quickly recurrent and associated with poor prognosis, the early diagnosis and the search for new therapeutic approaches is becoming mandatory. Instead of using “invasive” or “aggressive” adenoma, the term “tumor suspected of malignancy” would be used for more accuracy

Effect of Curcumin on Oxidative Stress in a Model of Turpentine Induced Acute Experimental Inflammation

Curcumin, a natural phenolic compound is an anti-tumor agent with anti-inflammatory and anti-oxidant properties. The aim of this research was to evaluate oxidative stress levels, the antioxidant activity and Curcumin concentrations by high performance liquid chromatography (HPLC) in an acute experimental inflammation induced by Turpentine oil (intramuscular 0.6 mg kg-1 body weight) and to compare a prophylactic versus a therapeutic regimen of Curcumin (oral suspension of 150 mg Curcumin kg-1 rat weight). Sixteen adult male Wistar rats were assigned to four groups: Control, Group I (Curcumin only), Group II (Curcumin administration, then induced inflammation after 1 hour) and Group III (induced inflammation then Curcumin administration after 2 hours). Oxidative stress was assessed by measuring serum malondialdehide and carbonylated proteins, while systemic and local total antioxidant capacity was determined by ABTS. Local tissue changes (muscle, kidney, liver) were analysed using histopathology. Results showed that acute inflammation significantly increased lipid peroxidation in Groups II and III compared to Control and Group I. A significantly reduced total antioxidant capacity (ATBS) was present in serum and kidney in Group II, also in muscle and kidney in Group III. ABTS levels were significantly increased only in the liver tissue of the animals in Groups II and III with induced inflammation as compared to Group I. This study proved the potential of Curcumin in reducing oxidative stress in both prophylactic and therapeutic regimens

Tooth Enamel, the Result of the Relationship between Matrix Proteins and Hydroxyapatite Crystals

Enamel, a structure of epithelial origin, represents a protective tooth cover. The cells responsible for the formation of enamel, ameloblasts, are lost at the time of tooth eruption, so that enamel becomes an acellular structure that can no longer regenerate. In order to compensate for this particular phenomenon, enamel has acquired a complex structural organization and a high mineralization degree, in its mature state. This reflects the particular life cycle of ameloblasts and the unique physico-chemical characteristics of matrix proteins, which regulate the formation of the extremely long crystals of enamel. These characteristics differentiate enamel from all the other tissues of the organism

Diffusion-Weighted Magnetic Resonance Imaging as a Noninvasive Parameter for Differentiating Benign and Malignant Intraperitoneal Collections

Background and Objective: The imaging differentiation of benign from malignant intraperitoneal collections (IPCs) relies on the tumoral morphological modifications of the peritoneum, which are not always advocating for malignancy. We aimed to assess ascitic fluid with the apparent diffusion coefficient (ADC) to determine non-invasive, stand-alone, differentiation criteria for benign and malignant intraperitoneal effusions. Materials and Methods: Sixty-one patients with known IPCs who underwent magnetic resonance examinations for reasons such as tumor staging, undetermined abdominal mass and disease follow up were retrospectively included in this study. All subjects had a final diagnosis of the fluid based on pathological examinations, which were divided into benign (n = 37) and malignant (n = 24) IPCs groups. ADC values were measured separately by two radiologists, and the average values were used for comparing the two groups by consuming the independent samples t-test. The receiver operating characteristic analysis was performed to test the ADC values’ diagnostic ability to distinguish malignant from benign collections. Results: The differentiation between benign and malignant IPCs based on ADC values was statistically significant (p = 0.0034). The mean ADC values were higher for the benign (3.543 × 10−3 mm2/s) than for the malignant group (3.057 × 10−3 mm2/s). The optimum ADC cutoff point for the diagnosis of malignant ascites was <3.241 × 10−3 mm2/s, with a sensitivity of 77.78% and a specificity of 80%. Conclusions: ADC represents a noninvasive and reproducible imaging parameter that may help to assess intraperitoneal collections. Although successful in distinguishing malignant from benign IPCs, further research must be conducted in order to certify if the difference in ADC values is a consequence of the physical characteristics of the ascitic fluids or their appurtenance to a certain histopathological group

The Impact of Monocyte to High-Density Lipoprotein Cholesterol Ratio on All-Cause and Cardiovascular Mortality in Patients with Transcatheter Aortic Valve Replacement

Background: Inflammation plays a significant role in the pathogenesis of aortic stenosis. This study aimed to investigate the prognostic value of the monocyte-HDL cholesterol ratio (MHR), a new inflammatory marker, in severe aortic stenosis (AS) patients who underwent transcatheter aortic valve replacement (TAVR). Methods: A total of 125 patients with severe AS who underwent TAVR were assessed. Clinical, echocardiographic and laboratory data relevant to the research were retrospectively obtained from the patients’ records. The MHR was determined by dividing the absolute monocyte count by the HDL-C value. The primary endpoints were overall and cardiovascular mortality. Results: During a median follow-up time of 39 months, primary endpoints were developed in 51 (40.8%) patients (overall mortality) and 21 (16.8%) patients (cardiovascular mortality). A receiver operating characteristic (ROC) analysis showed that by using a cut-off level of 16.16, the MHR predicted the all-cause mortality with a sensitivity of 50.9% and specificity of 89.1%. In predicting cardiovascular mortality, the MHR exhibited a sensitivity of 80.9% and specificity of 70.1% when a cut-off level of 13.56 was used. In the multivariate analysis, the MHR (p p = 0.018; 95% CI: 1.11–3.38) were found to be significant predictors of overall mortality. Conclusions: This study showed a significant elevation in the MHR among patients who experienced all-cause and cardiovascular mortality and this ratio emerged as an independent predictor of all-cause death in patients with severe AS undergoing TAVR

Uterine Artery Doppler Ultrasonography for First Trimester Prediction of Preeclampsia in Individuals at Risk from Low-Resource Settings

Background and objectives: The objective of this study was to evaluate the potential of first trimester uterine artery Doppler ultrasonography for the early prediction of preeclampsia (PE), in at-risk pregnant women. Materials and Methods: This was a prospective longitudinal study, including 120 Caucasian pregnant women with risk factors for PE. The potential of pulsatility indexes (PI) and notch was assessed as a tool for preeclampsia screening. Results: Doppler examination of the uterine artery performed early at 11–14 WA allows the detection of pregnancies that will develop PE with a sensitivity of 61.5% and a specificity of 63.8% based on PI analysis. Predictive power increases slightly by adding bilateral notch (sensitivity = 65.4%; specificity = 66%). Conclusions: Uterine artery Doppler examination is an effective non-invasive screening test for the development of PE in pregnancies at risk, particularly appropriate in health systems with limited means of evaluating other biomarkers

Ultrasonography in the Diagnosis of Adnexal Lesions: The Role of Texture Analysis

The classic ultrasonographic differentiation between benign and malignant adnexal masses encounters several limitations. Ultrasonography-based texture analysis (USTA) offers a new perspective, but its role has been incompletely evaluated. This study aimed to further investigate USTA’s capacity in differentiating benign from malignant adnexal tumors, as well as comparing the workflow and the results with previously-published research. A total of 123 adnexal lesions (benign, 88; malignant, 35) were retrospectively included. The USTA was performed on dedicated software. By applying three reduction techniques, 23 features with the highest discriminatory potential were selected. The features’ ability to identify ovarian malignancies was evaluated through univariate, multivariate, and receiver operating characteristics analyses, and also by the use of the k-nearest neighbor (KNN) classifier. Three parameters were independent predictors for ovarian neoplasms (sum variance, and two variations of the sum of squares). Benign and malignant lesions were differentiated with 90.48% sensitivity and 93.1% specificity by the prediction model (which included the three independent predictors), and with 71.43–80% sensitivity and 87.5–89.77% specificity by the KNN classifier. The USTA shows statistically significant differences between the textures of the two groups, but it is unclear whether the parameters can reflect the true histopathological characteristics of adnexal lesions

A Pilot Study of Multiplex Ligation-Dependent Probe Amplification Evaluation of Copy Number Variations in Romanian Children with Congenital Heart Defects

Congenital heart defects (CHDs) have had an increasing prevalence over the last decades, being one of the most common congenital defects. Their etiopathogenesis is multifactorial in origin. About 10–15% of all CHD can be attributed to copy number variations (CNVs), a type of submicroscopic structural genetic alterations. The aim of this study was to evaluate the involvement of CNVs in the development of congenital heart defects. We performed a cohort study investigating the presence of CNVs in the 22q11.2 region and GATA4, TBX5, NKX2-5, BMP4, and CRELD1 genes in patients with syndromic and isolated CHDs. A total of 56 patients were included in the study, half of them (28 subjects) being classified as syndromic. The most common heart defect in our study population was ventricular septal defect (VSD) at 39.28%. There were no statistically significant differences between the two groups in terms of CHD-type distribution, demographical, and clinical features, with the exceptions of birth length, weight, and length at the time of blood sampling, that were significantly lower in the syndromic group. Through multiplex ligation-dependent probe amplification (MLPA) analysis, we found two heterozygous deletions in the 22q11.2 region, both in patients from the syndromic group. No CNVs involving GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes were identified in our study. We conclude that the MLPA assay may be used as a first genetic test in patients with syndromic CHD and that the 22q11.2 region may be included in the panels used for screening these patients