Gastroenteropancreatic neuroendocrine neoplam (GEP-NEN) is a rare group of tumors with its incidence rising significantly in recent decades. Because of the late presentation of the disease and limitations in conventional biomarkers, about 50% of GEP-NEN patients manifests advanced disease when diagnosed. Therefore, it is vital to identify circulating biomarkers which can not only be used for early diagnosis but also accurately evaluating the biological behavior of GEP-NEN. This review summarizes the advances of circulating biomarkers in diagnosing and evaluating efficacy of treatment in GEP-NEN. Well-known circulating biomarkers include chromogranin A (CgA), pancreastatin (PST), chromogranin B (CgB), neuron-specific enolase (NSE) and pancreatic peptide(PP). Novel biomarkers including circulating tumor cell(CTC), microRNA and NETest are promising biomarkers with potential clinical benefit, but further researches are needed before their clinical applications.
Biomarkers, Tumor ; blood ; Chromogranin A ; blood ; Chromogranin B ; blood ; chemistry ; Gastrointestinal Neoplasms ; blood ; chemistry ; diagnosis ; genetics ; Humans ; MicroRNAs ; blood ; Neoplastic Cells, Circulating ; Neuroendocrine Tumors ; blood ; chemistry ; diagnosis ; genetics ; Pancreatic Neoplasms ; blood ; chemistry ; diagnosis ; genetics ; Pancreatic Polypeptide ; blood ; Phosphopyruvate Hydratase ; blood

PURPOSE: Although lavender is purported to possess anxiolytic and sedative properties and is often recommended for relieving anxiety, the efficacy of lavender has not been well established. Thus, this review aimed to evaluate the anxiolytic effects of lavender aromatherapy.METHODS: Ten data bases were searched for studies published between 2000 and 2018. Randomized controlled trials investigating the anxiolytic effects of lavender aromatherapy with any type of application for persons with or without clinical anxiety were included. The outcome variables included self-rated anxiety, vital signs, and salivary cortisol and chromogranin A (CgA) levels. In the meta-analysis, standardized mean difference and 95% confidence interval were calculated as effect measures by applying the random effect model and inverse variance method.RESULTS: Twenty-two trials met our inclusion criteria. Lavender aromatherapy was found to have favorable effects in relieving anxiety (Hedges' ĝ = −0.65; 95% CI, −0.84 to −0.46) and decreasing systolic blood pressure (ĝ = −0.22; 95% CI, −0.43 to −0.02), heart rate (ĝ = −0.53; 95% CI, −0.74 to −0.32), and salivary cortisol (ĝ = −1.29; 95% CI, −2.23 to −0.35) and CgA (ĝ = −2.29; 95% CI, −3.24 to −1.34) levels. However, the meta-analysis did not reveal any significant effects of lavender on diastolic blood pressure (effect size: −0.17; 95% CI, −0.37e0.04).CONCLUSION: Aromatherapy using lavender oil might have favorable effects on anxiety and its physiological manifestations. Future studies are recommended with an emphasis on methodological quality. In nursing practice, it is suggested that lavender aromatherapy be included in programs intended to manage anxiety in patients across diverse healthcare settings.
Anti-Anxiety Agents ; Anxiety ; Aromatherapy ; Blood Pressure ; Chromogranin A ; Delivery of Health Care ; Heart Rate ; Humans ; Hydrocortisone ; Lavandula ; Methods ; Nursing ; Vital Signs

No abstract available.
Anti-Ulcer Agents/*therapeutic use ; Chromogranin A/*blood ; Combined Modality Therapy ; Gastrins/*blood ; Ghrelin/*blood ; Histamine H2 Antagonists/*therapeutic use ; Humans ; Proton Pump Inhibitors/*therapeutic use

OBJECTIVETo examine the changes in serum chromogranin A (CgA) and urotensin II (U II) levels in children with chronic heart failure (CHF) and their clinical significance.

METHODSA total of 58 children with CHF, among whom 17 had endocardial fibroelastosis (EFE) and 41 had dilated cardiomyopathy (DCM), were selected as CHF group, and 20 healthy children were selected as control group. Serum levels of CgA and U II were measured using enzyme-linked immunosorbent assay, and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined by bi-directional lateral flow immunoassay. Ventricular remodeling indices were measured using echocardiography. The correlation between serum CgA and U II levels and ventricular remodeling was evaluated by Pearson correlation or Spearman's rank correlation analysis.

RESULTSThere were no significant differences in serum CgA and NT-proBNP levels between children with grade II heart function and the control group (P>0.05). However, the serum CgA and NT-proBNP levels gradually increased as the heart function grade increased, and were significantly higher in grade III and IV children compared to those in the control group (P<0.05). U II levels were lower in children with grade II, III, or IV heart function than those in the control group (P<0.05), and significantly decreased with the aggravation of CHF (P<0.05). There were no significant differences in CgA and U II levels between patients with EFE and DCM (P>0.05). Serum CgA concentration was positively correlated with left ventricular mass index (LVMI), NT-proBNP, and cardiac function classification (r=0.279, 0.649, and 0.778 respectively; P<0.05), but was negatively correlated with left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and U II (r=-0.369, -0.322, and -0.718 respectively; P<0.05). Serum U II concentration was negatively correlated with NT-proBNP and cardiac function classification (r=-0.472 and -0.591 respectively; P<0.05), but was not correlated with LVMI, LVEF, and LVFS (P>0.05).

CONCLUSIONSCgA may play a role in ventricular remodeling in children with CHF. Serum CgA and U II may serve as a reference for the diagnosis and functional classification of heart failure.

Cardiomyopathy, Dilated ; blood ; Child ; Child, Preschool ; Chromogranin A ; blood ; Chronic Disease ; Endocardial Fibroelastosis ; blood ; Female ; Heart Failure ; blood ; Humans ; Infant ; Male ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Urotensins ; blood ; Ventricular Function, Left

Chromogranin A (CgA) is widely used as an immunohistochemical marker of neuroendocrine neoplasms and has been measurable in plasma of patients. We assessed the clinical role of plasma CgA in diagnosing pancreatic neuroendocrine neoplasm (PNEN). CgA was checked in 44 patients with pancreatic mass who underwent surgical resection from 2009 through 2011. The cutoff value for diagnosing PNEN and the relationships between CgA and clinicopathologic variables were analyzed. Twenty-six patients were PNENs and 18 patients were other pancreatic disorders. ROC analysis showed a cutoff of 60.7 ng/mL with 77% sensitivity and 56% specificity, and the area under the curve (AUC) was 0.679. Among PNEN group, the sensitivity and specificity of diagnosing metastasis were 100% and 90% respectively when CgA cutoff was 156.5 ng/mL. The AUC was 0.958. High Ki-67 index (160.8 vs 62.1 ng/mL, P = 0.001) and mitotic count (173.5 vs 74.6 ng/mL, P = 0.044) were significantly correlated with plasma CgA, but the tumor size was not. In conclusion, CgA has a little value in diagnosing PNEN. However, the high level of CgA (more than 156.5 ng/mL) can predict the metastasis. Also, plasma CgA level correlates with Ki-67 index and mitotic count which represents prognosis of PNENs.
Adolescent ; Adult ; Aged ; Area Under Curve ; Chromogranin A/*blood ; Female ; Humans ; Male ; Middle Aged ; Neuroendocrine Tumors/blood/*diagnosis/pathology ; Pancreatic Neoplasms/blood/*diagnosis/pathology ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; Young Adult

BACKGROUND/AIMS: Long-term use of proton pump inhibitor (PPI) induces hypergastrinemia, which results from the suppression of gastric acid secretion. Hypergastrinemia causes enterochromaffin-like (ECL) cell hyperplasia, which is a predisposing factor of carcinoid tumor of stomach. The aim of this study was to identify the effect of long-term gastric acid suppression on the gastric peptides levels, such as gastrin, chromogranin A, or ghrelin. METHODS: Control group included patients who had no medication over six months. Both H2RA (H2 receptor antagonist) and PPI groups had medication at least for six months. Fasting blood was taken from each patient to assay serum gastrin, chromogranin A, and ghrelin by RIA and ELISA techniques. RESULTS: The patients with the above reference range of serum gastrin and chromogranin A were more commonly found in PPI group compared to control and H2RA group. However, serum ghrelin level was within the reference range in all the patients regardless of groups. There was no difference in the ratio of serum gastrin/chromogranin A among three groups. Both average serum levels of gastrin and chromogranin A were significantly elevated in PPI group compared to control and H2RA group. There was a significant correlation between the level of serum gastrin and chromogranin A. CONCLUSIONS: Long-term administration of H2RA does not affect the serum gastrin and chromogranin A level. However, long-term administration of PPI increases serum gastrin and chromogranin A. Ghrelin may influence gastric acid secretion in other pathway than ECL cell-mediated pathway such as gastrin or chromogranin A.
Adult ; Aged ; Anti-Ulcer Agents/*therapeutic use ; Chromogranin A/*blood ; Female ; Gastrins/*blood ; Ghrelin/*blood ; Histamine H2 Antagonists/*therapeutic use ; Humans ; Male ; Middle Aged ; Proton Pump Inhibitors/*therapeutic use ; Time Factors

OBJECTIVETo determine whether circulating level of catestatin (CST) could provide prognostic information independently of conventional risk markers for the development of in-hospital heart failure in patients with ST-segment elevation myocardial infarction (STEMI).

METHODSThe data of 120 STEMI patients (mean age: 61 years, 73% male) were collected from the Second Hospital of Shanxi Medical University and Taiyuan Central Hospital between November 2010 and September 2011.The patients were categorized into 4 groups according to CST (ng/L) quartile: ≤ 74.72, 74.73-79.67, 79.68 - 84.21 and ≥ 84.22 ng/L. Clinical features, therapeutic approaches were compared among groups. The patients were also grouped according to Killip class: Killip level I (n = 68), Killip level II (n = 23), Killip level III (n = 18), Killip level IV (n = 11). CST, NE and NT-proBNP were compared among groups. The Spearma rank correlation and multivariate logistic regression analysis were applied to determine the association between risk factors and in-hospital heart failure. Receiver-operator characteristic (ROC) curve was performed to evaluate the power of CST and NT-proBNP on predicting in-hospital heart failure.

RESULTSGender, hospital days, past history of smoking, hypertension, myocardial infarction, CK-MB peak level, TnI peak level, heart rate, blood pressure, blood glucose, blood lipid levels on admission and early reperfusion therapy were similar among groups. Patients with higher CST values were more likely to be older, to have lower body mass index, to have higher white blood cell count, CysC, hs-CRP, NE, NT-proBNP, past history of angina, diabetes mellitus, being diuretic users, and to have a lower ejection fraction (all P < 0.05). Higher CST levels were also associated with increased risk of heart failure (P < 0.05). In proportion with the deterioration of the cardiac function, CST, NE, NT-proBNP concentration gradually increased (all P < 0.05). Spearman rank correlation analysis showed that the CST was negatively correlated with LVEF (r(s) = -0.923, P < 0.001) and positively correlated with NT-proBNP (r(s) = 0.884, P < 0.001). After multivariate adjustment, CST remained to be an independent risk factor for the development of in-hospital heart failure (OR = 1.125, 95%CI: 1.056 - 1.198;P < 0.001). The area under the ROC curve of CST and NT-proBNP was 0.777 and 0.874. Using CST = 77.29 ng/L as a cut-off value, the sensitivity was 92.8% and specificity was 70.6% for predicting the development of in-hospital heart failure.

CONCLUSIONThe plasma CST level is an independent predictor for the development of in-hospital heart failure in patients with STEMI.

Aged ; Catechols ; antagonists & inhibitors ; pharmacology ; Chromogranin A ; blood ; Female ; Heart Failure ; diagnosis ; etiology ; Humans ; Inpatients ; Male ; Middle Aged ; Myocardial Infarction ; blood ; complications ; diagnosis ; Peptide Fragments ; blood ; Prognosis ; Prospective Studies ; Risk Factors

OBJECTIVETo evaluate the significance of the combined assay of chromogranin A (CgA) and prostate specific antigen (PSA) in the diagnosis of prostate cancer.

METHODSSerum CgA and PSA were detected by ELISA technique in 55 cases of prostate cancer (PCa), 25 cases of benign prostate hyperplasia (BPH), and 50 cases of normal subjects (control).

RESULTSThe serum CgA level in the PCa group was significantly higher than those in the control and BPH groups (P < 0.05), and increased with clinical stages. The parallel and serial tests associated with serum PSA and CgA raised the rate of detection of prostate cancer.

CONCLUSIONThe combined assay of serum PSA and CgA is of significant clinical value in raising the rate of diagnosis of prostate cancer, as well as in staging and prognosing the disease.

Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Case-Control Studies ; Chromogranin A ; blood ; Enzyme-Linked Immunosorbent Assay ; Humans ; Male ; Middle Aged ; Prognosis ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; diagnosis ; Sensitivity and Specificity

Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome. A 35-year-old female was referred to our hospital with recurrent acute pancreatitis. On radiologic studies, 1.5 cm sized mass was noted in pancreas tail. Cytological evaluation with EUS-fine-needle aspiration suggested serous cystadenoma. She received distal pancreatectomy. The histologic examination revealed a 1.7 cm sized neuroendocrine tumor positive for immunohistochemical staining with glucagon antibody. Multiple glucagon-producing micro endocrine cell tumors were scattered next to the main tumor. Additionally, diffuse hyperplasia of pancreatic islets and ectopic proliferation of islet cells in centroacinar area, findings compatible to nesidioblastosis, were seen. These hyperplasia and almost all nesidioblastic cells were positive for glucagon immunochemistry. Even though serum glucagon level still remained higher than the reference value, she has been followed-up without any evidence of recurrence or hormone related symptoms. Herein, we report a case of alpha-cell nesidioblastosis and hyperplasia combined with glucagon-producing neuroendocrine tumor with literature review.
Adult ; Chromogranin A/blood ; Female ; Glucagon/*metabolism ; Glucagon-Secreting Cells/metabolism ; Humans ; Hyperplasia/complications/*diagnosis ; Islets of Langerhans/metabolism/ultrasonography ; Nesidioblastosis/complications/*diagnosis ; Neuroendocrine Tumors/complications/*diagnosis/pathology ; Pancreas/*pathology ; Tomography, X-Ray Computed

Catecholamine secretory traits were significantly heritable, as were stress-induced blood pressure changes. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis. In the tyrosine hyroxylase promoter, significant associations were found for urinary catecholamine excretion and for blood pressure response to stress. TH promoter haplotype 2 (TGGG) showed pleiotropy, increasing both norepinephrine excretion and blood pressure during stress. In hypertension, 2 independent case-control studies (1,266 subjects with 53% women and 927 subjects with 24% women) replicated the effect of C-824T in the determination of blood pressure. Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in the storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive kidney disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed such regulatory regions as the proximal promoter and 3'-UTR. In chromaffin cell-transfected CHGA 3'-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 3'-UTR displayed statistical associations with hypertension and hypertensive end stage renal disease. Therefore, I would like to review the common genetic variation in TH and CHGA as a cause of inter-individual variation in sympathetic activity, and ultimately blood pressure and hypertensive kidney disease.
Blood Pressure ; Case-Control Studies ; Chromogranin A ; Female ; Genetic Variation ; Genomics ; Haplotypes ; Humans ; Hypertension ; Kidney ; Kidney Diseases ; Kidney Failure, Chronic ; Norepinephrine ; Plasmids ; Regulatory Sequences, Nucleic Acid ; Secretory Vesicles ; Tyrosine ; Tyrosine 3-Monooxygenase ; Organelle Biogenesis