Carcinoid syndroma - diagnosis and management.

Neuroendocrine tumors (NETs, originally termed “carcinoids”) create a relatively rare group of neoplasms with an approximate incidence rate of 5 to 8 cases per 10 000 persons. NETs predominantly demonstrate indolent disease biology for many years. They become symptomatic when they are large enough or when they metastasize to the liver or the lungs, bones, or other sites. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome. Signs and symptoms of carcinoid syndrome are bronchospasm, flushing, diarrhea and cramping, cyanosis and pellagra. White plaque-like deposits on the endocardial surface of heart structures are characteristic for carcinoid heart disease. The treatment of patients with carcinoid syndrome is multi-faceted due to the necessity to manage simultaneously the systemic cancer disease as well as the signs of carcinoid syndrome and includes resection or debulking of tumor mass, biological treatment with somatostatin analogues and peptide receptor radionuclide treatment.

Simultaneous Immunodetection of Anthrax, Plague, and Tularemia from Blood Cultures by Use of Multiplexed Suspension Arrays.

Multiplexed detection technologies are becoming increasingly important given the possibility of bioterrorism attacks, for which the range of suspected pathogens can vary considerably. In this work, we describe the use of Luminex MagPlex magnetic microspheres for the construction of two multiplexed diagnostic suspension arrays, enabling antibody-based detection of bacterial pathogens and their related disease biomarkers directly from blood cultures. The first 4-plex diagnostic array enabled the detection of both anthrax and plague infections using soluble disease biomarkers, including protective antigen (PA) and anthrax capsular antigen for anthrax detection and the capsular F1 and LcrV antigens for plague detection. The limits of detection (LODs) ranged between 0.5 and 5 ng/ml for the different antigens. The second 2-plex diagnostic array facilitated the detection of Yersinia pestis (LOD of 1 × 106 CFU/ml) and Francisella tularensis (LOD of 1 × 104 CFU/ml) from blood cultures. Inoculated, propagated blood cultures were processed (15 to 20 min) via 2 possible methodologies (Vacutainer or a simple centrifugation step), allowing the direct detection of bacteria in each sample, and the entire assay could be performed in 90 min. While detection of bacteria and soluble markers from blood cultures using PCR Luminex suspension arrays has been widely described, to our knowledge, this study is the first to demonstrate the utility of the Luminex system for the immunodetection of both bacteria and soluble markers directly from blood cultures. Targeting both the bacterial pathogens as well as two different disease biomarkers for each infection, we demonstrated the benefit of the multiplexed developed assays for enhanced, reliable detection. The presented arrays could easily be expanded to include antibodies for the detection of other pathogens of interest in hospitals or labs, demonstrating the applicability of this technology for the accurate detection and confirmation of a wide range of potential select agents.

[Management of treatment in patients with neuroendocrine neoplasmas of digestive tract]. / Manazment liecby pacientov s neuroendokrinnými nádormi tráviaceho traktu.

UNLABELLED: Neuroendocrine neoplasmas are a form of cancer arising from cells of diffuse neuroendocrine system. They produce peptides or amines that act as hormones or neurotransmitters. Incidence of NENs is relatively low. Diagnostic work-up and treatment requires a multidisciplinary team approach. The aim of this study was an analysis of data from patients with well-differentiated neuroendocrine neoplasmas of gastrointestinal tract. The study included patients followed up from 1998 to 2013 with histologically confirmed well-differentiated digestive neuroendocrine neoplasm with low or intermediate malignant potential. 97 patients were included; 34 men (35.1 %) and 63 women (64.9 %). In patients being diagnosed after 2005 interferon treatment is significantly less used than endoscopic and peptide receptor radionuclide therapy. We have identified more appropriate discriminant values of 5-HIAA and chromogranin A (6.8 mg/24 hours; 70 ng/ml) for predicting the presence of metastases at the time of diagnosis. We have identified following risk factors for overall mortality: liver metastases, presence of diarrhea, flush, small bowel primary tumor, high values of CgA and 5-HIAA at the time of diagnosis (5-HIAA > 520.52 mg/24 hours, CgA > 174.5 ng/ml). Surgical treatment was found to be a positive prognostic factor. KEY WORDS: chromogranin A - 5-hydroxyindoleacetic acid - neuroendocrine neoplasm.

[Management of treatment in patients with neuroendocrine neoplasmas of digestive tract]. / Manazment liecby pacientov s neuroendokrinnými nádormi tráviaceho traktu.

Neuroendocrine neoplasmas are a form of cancer arising from cells of diffuse neuroendocrine system. They produce peptides or amines that act as hormones or neurotransmitters. Incidence of NENs is relatively low. Diagnostic work-up and treatment requires a multidisciplinary team approach. The aim of this study was an analysis of data from patients with well-differentiated neuroendocrine neoplasmas of gastrointestinal tract. The study included patients followed up from 1998 to 2013 with histologically confirmed well-differentiated digestive neuroendocrine neoplasm with low or intermediate malignant potential. 97 patients were included; 34 men (35.1%) and 63 women (64.9%). In patients being diagnosed after 2005 interferon treatment is significantly less used than endoscopic and peptide receptor radionuclide therapy. We have identified more appropriate discriminant values of 5-HIAA and chromogranin A (6.8 mg/24 hours; 70 ng/ml) for predicting the presence of metastases at the time of diagnosis. We have identified following risk factors for overall mortality: liver metastases, presence of diarrhea, flush, small bowel primary tumor, high values of CgA and 5-HIAA at the time of diagnosis (5-HIAA > 520.52 mg/24 hours, CgA > 174.5 ng/ml). Surgical treatment was found to be a positive prognostic factor.

Epitope Binning of Novel Monoclonal Anti F1 and Anti LcrV Antibodies and Their Application in a Simple, Short, HTRF Test for Clinical Plague Detection.

Mouse monoclonal antibodies were raised against plague disease biomarkers: the bacterial capsular protein fraction 1 (F1) and the low-calcium response-LcrV virulence factor (Vag). A novel tandem assay, employing BioLayer Interferometry (BLI), enabled the isolation of antibodies against four different epitopes on Vag. The tandem assay was carried out with hybridoma supernatants, circumventing the need for antibody purification. The BioLayer assay was further adopted for characterization of epitope-repetitive antigens, enabling the discovery of two unique epitopes on F1. The selected antibodies were purified and applied as "oligo-clonal" reagents for the immuno-detection of both biomarkers. The developed Homogenous Time Resolved Fluorescence (HTRF) tests were short (10 min) and simple (no washing steps), allowing for detection of 10 ng/mL F1 and 2.5 ng/mL Vag. The tests were successfully applied for detection of disease biomarkers produced by various Y. pestis strains during growth in blood culture vials.

Abnormalities in the relationship of paraoxonase 1 with HDL and apolipoprotein A1 and their possible connection to HDL dysfunctionality in type 2 diabetes.

AIMS: Lipid parameters, lipid risk indexes and lipid-related oxidative stress markers (paraoxonase 1 [PON1] and lipid peroxides [LPO]) reflect the actual status of lipid metabolism in type 2 diabetes (T2DM). We hypothesized that relationships of high-density lipoprotein cholesterol (HDL-c) with PON1 and apolipoprotein A1 (ApoA1) and/or PON1 with ApoA1 under conditions of hyperglycaemia and oxidative stress might reveal HDL functionality. We investigated relationships between PON1, LPO, and lipid risk markers in T2DM subjects and compared them with those in healthy subjects. METHODS: A total of 107 Caucasian subjects, 67 T2DM outpatients (mean age 52.2 ±â€¯6.9 years) and 40 healthy subjects (mean age 48.1 ±â€¯7.5 years) were included in the study. Serum levels of total cholesterol (CHOL-T), HDL-c, low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), apolipoprotein B (ApoB), ApoA1, LPO, and PON1 activity were measured. Non-HDL-c, ApoB/ApoA1 and non-HDL/HDL (lipid risk indexes) were calculated. RESULTS: Higher levels of TG, LPO (P < 0.0001), nonHDL/HDL and ApoB/ApoA1 (P < 0.001, 0.05, respectively), and lower levels of HDL-c, ApoA1, and PON1 (P < 0.0001) were observed in T2DM subjects than in controls. There is a lack of relationship among PON1, HDL-c, and ApoA1 in T2DM patients. PON1 activity positively correlated with these parameters (P < 0.0001) in controls. Strong correlations between non-HDL-c and ApoB (r = 0.956 vs. 0.756; P < 0.0001), LPO and TG (r = 0.831 vs. 0.739; P < 0.0001) were recorded in both study groups (P < 0.0001). CONCLUSIONS: Impaired anti-oxidant and anti-atherogenic HDL properties associated with weakened PON1 function and lipid peroxidation may contribute to the development of atherosclerosis-related diseases in T2DM.

Tailored intermittent therapy of carcinoid.

BACKGROUND/AIMS: There is no established standard care of carcinoids as all experts agree. Endogenous somatostatin diurnal rhythm is influenced by administration of lanreotid. The purpose of this study is to evaluate efficacy of lanreotid on the clinical course in a group of patients with metastatic carcinoid. METHODOLOGY: In 43 patients with carcinoid tumors somatostatin serum level, 5-HIAA (5-hydroxyindolacetic acid), NSE (neuron-specific enolase), and chromogranin A were examined. Fifteen patients received 30mg of somatulin (Lanreotid) in two-week intervals. RESULTS: Therapy with somatostatin analogue improved symptoms in 70-80% of patients with metastases and carcinoid syndrome. 5-HIAA significantly decreased after lanreotid therapy. NSE values are undulating. With progression of the disease they rise. Chromogranin is higher in patients with advanced metastatic disease. Mesor of the diurnal excretion of somatostatin is higher (32 pg/mL) in patients with metastatic disease than in patients without (20 pg/mL). After lanreotid administration mesor decreased (16 pg/mL) in the group of patients with metastases. CONCLUSIONS: Intermittent lanreotid therapy is efficient. A rise--(ascend) of endogenous SMS level could be one of the markers of increased activity of carcinoid cells and an indication for the next application of lanreotid therapy. Mean survival of patients with metastatic carcinoid in our study was 46.3 months.