A nomogram consisted of routine biochemical tests may increase the diagnostic accuracy of chromogranin A in detecting patients with neuroendocrine tumors

Chromogranin A (CgA) is the most widely accepted biomarker for neuroendocrine tumors (NET) but its diagnostic accuracy is dependent on tumor type and the use of proton-pump inhibitors (PPI). We investigated the diagnostic value of circulating miRNAs along with CgA in pancreatic neuroendocrine tumors (pNET). 74 serum samples from patients with pNET (n = 25, nonfunctioning), pheochromocytoma/paraganglioma (PPGL, n = 20), healthy individuals with normal CgA (n = 29) including 10 samples from 5 healthy individuals with and without current PPI treatment were collected. MiRNA expression profiles were determined using next-generation sequencing, followed by validation with individual TaqMan assays. A global downregulation of miRNAs was observed in patients with NET compared to controls. MiRNA expression of 33 miRNAs was able to discriminate tumor samples from controls. No miRNA alone could be considered as an applicable biomarker for pNET or PPGL. However, using a logistic model, the combination of a set of miRNAs increased the discriminatory role of CgA irrespective of PPI treatment. In pNET patients with normal CgA level our regression model yielded high (89.4%) diagnostic accuracy (AUC: 0.904, sensitivity: 66.6%, specificity: 96.5%). A set of miRNAs increased the diagnostic utility of CgA in pNET even in patients with low CgA.

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Pre-operative Diagnosis of Pancreatic Neuroendocrine Tumors with Endoscopic Ultrasonography and Computed Tomography in a Large Series

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.253.ned ◽

2016 ◽

Vol 25 (3) ◽

pp. 317-321 ◽

Cited By ~ 16

Author(s):

Raffaele Manta ◽

Elisabetta Nardi ◽

Nico Pagano ◽

Claudio Ricci ◽

Mariano Sica ◽

...

Keyword(s):

Computed Tomography ◽

Neuroendocrine Tumors ◽

Endoscopic Ultrasonography ◽

Fine Needle Aspiration ◽

Chromogranin A ◽

Needle Aspiration ◽

Large Series ◽

Tumor Diameter ◽

Pancreatic Neuroendocrine Tumors ◽

Fine Needle

Background & Aims: Diagnosis of pancreatic neuroendocrine tumors (p-NETs) is frequently challenging. We describe a large series of patients with p-NETs in whom both pre-operative Computed Tomography (CT) and Endoscopic Ultrasonography (EUS) were performed. Methods: This was a retrospective analysis of prospectively collected sporadic p-NET cases. All patients underwent both standard multidetector CT study and EUS with fine-needle aspiration (FNA). The final histological diagnosis was achieved on a post-surgical specimen. Chromogranin A (CgA) levels were measured. Results: A total of 80 patients (mean age: 58 ± 14.2 years; males: 42) were enrolled. The diameter of functioning was significantly lower than that of non-functioning p-NETs (11.2 ± 8.5 mm vs 19.8 ± 12.2 mm; P = 0.0004). The CgA levels were more frequently elevated in non-functioning than functioning pNET patients (71.4% vs 46.9%; P = 0.049). Overall, the CT study detected the lesion in 51 (63.7%) cases, being negative in 26 (68.4%) patients with a tumor ≤10 mm, and in a further 3 (15%) cases with a tumor diameter ≤20 mm. CT overlooked the pancreatic lesion more frequently in patients with functioning than non-functioning p-NETs (46.5% vs 24.3%; P = 0.002). EUS allowed a more precise pre-operative tumor measurement, with an overall incorrect dimension in only 9 (11.2%) patients. Of note, the EUS-guided FNA suspected the neuroendocrine nature of tumor in all cases. Conclusions: Data of this large case series would suggest that the EUS should be included in the diagnostic work-up in all patients with a suspected p-NET, even when the CT study was negative for a primary lesion in the pancreas.– . Abbrevations: CgA: chromogranin A; EUS: Endoscopic Ultrasonography; FNA: fine-needle aspiration; p-NETs: pancreatic neuroendocrine tumors.

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Quantification of chromogranin A with a surface plasmon resonance-based biosensor

Analytical Methods ◽

10.1039/d1ay00782c ◽

2021 ◽

Author(s):

Yang Xiao ◽

Yang Tai ◽

Xin Quan ◽

Chong Zhao ◽

Rui Liu ◽

...

Keyword(s):

Surface Plasmon Resonance ◽

Surface Plasmon ◽

Neuroendocrine Tumors ◽

Plasmon Resonance ◽

Chromogranin A ◽

Traditional Methods

The chromogranin A (CgA) level in the blood is an important biomarker for neuroendocrine tumors and other diseases. Traditional methods for detecting CgA are expensive and time-consuming with low reproducibility....

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Preoperative serum chromogranin-a is predictive of survival in locoregional jejuno-ileal small bowel neuroendocrine tumors

Surgery ◽

10.1016/j.surg.2021.01.048 ◽

2021 ◽

Author(s):

Praveen D. Chatani ◽

John G. Aversa ◽

James D. McDonald ◽

Tahsin M. Khan ◽

Xavier M. Keutgen ◽

...

Keyword(s):

Small Bowel ◽

Neuroendocrine Tumors ◽

Chromogranin A ◽

Preoperative Serum

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Chromogranin a Measurement in Neuroendocrine Tumors

The International Journal of Biological Markers ◽

10.1177/172460089801300102 ◽

1998 ◽

Vol 13 (1) ◽

pp. 3-9 ◽

Cited By ~ 14

Author(s):

L. Ferrari ◽

E. Seregni ◽

A. Martinetti ◽

B Van Graafeiland ◽

S. Nerini-Molteni ◽

...

Keyword(s):

Tumor Marker ◽

Neuroendocrine Tumors ◽

Chromogranin A ◽

High Sensitivity ◽

Biologically Active ◽

Proliferative Index ◽

Favorable Prognosis ◽

Blood Marker ◽

Active Substances

Neuroendocrine tumors (NETs) are rare neoplasms characterized by a low proliferative index and, in some cases, a favorable prognosis. These tumors often overproduce and release biologically active substances that are responsible for severe syndromes. Tumor marker measurement provides the clinician with useful information for the management of NET patients. The substances released by overproducing tumors are currently used as biomarkers, but there is a need for sensitive markers also for the “biochemically silent” NETs. The most effective and reliable blood marker available today is chromogranin A (CgA). Because of its high sensitivity and specificity, this glycoprotein can be used for the diagnosis, prognosis and follow-up of NETs. Furthermore, CgA measurement can be used for monitoring those tumors not overproducing or releasing any hormones or biological amines. This paper is a synthetic review on the value of CgA in NET management and reports our experiences with CgA measurement in NET patients.

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Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors

Cancer ◽

10.1002/(sici)1097-0142(19990901)86:5<858::aid-cncr23>3.0.co;2-8 ◽

1999 ◽

Vol 86 (5) ◽

pp. 858-865 ◽

Cited By ~ 168

Author(s):

Emilio Bajetta ◽

Leonardo Ferrari ◽

Antonia Martinetti ◽

Luigi Celio ◽

Giuseppe Procopio ◽

...

Keyword(s):

Acetic Acid ◽

Carcinoembryonic Antigen ◽

Neuroendocrine Tumors ◽

Chromogranin A ◽

Neuron Specific Enolase

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Chromogranin A: From Laboratory to Clinical Aspects of Patients with Neuroendocrine Tumors

International Journal of Endocrinology ◽

10.1155/2018/8126087 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 15

Author(s):

Paola Di Giacinto ◽

Francesca Rota ◽

Laura Rizza ◽

Davide Campana ◽

Andrea Isidori ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Phase Ii ◽

Chromogranin A ◽

Carcinoid Syndrome ◽

Phase Ii Trial ◽

Randomized Study ◽

Clinical Aspects ◽

Clinical Activity ◽

Octreotide Lar ◽

Well Differentiated

Background. Neuroendocrine tumors (NETs) are characterized by having behavior and prognosis that depend upon tumor histology, primary site, staging, and proliferative index. The symptoms associated with carcinoid syndrome and vasoactive intestinal peptide tumors are treated with octreotide acetate. The PROMID trial assesses the effect of octreotide LAR on the tumor growth in patients with well-differentiated metastatic midgut NETs. The CLARINET trial evaluates the effects of lanreotide in patients with nonfunctional, well-, or moderately differentiated metastatic enteropancreatic NETs. Everolimus has been approved for the treatment of advanced pancreatic NETs (pNETs) based on positive PFS effects, obtained in the treated group. Sunitinib is approved for the treatment of patients with progressive gastrointestinal stromal tumor or intolerance to imatinib, because a randomized study demonstrated that it improves PFS and overall survival in patients with advanced well-differentiated pNETs. In a phase II trial, pasireotide shows efficacy and tolerability in the treatment of patients with advanced NETs, whose symptoms of carcinoid syndrome were resistant to octreotide LAR. An open-label, phase II trial assesses the clinical activity of long-acting repeatable pasireotide in treatment-naive patients with metastatic grade 1 or 2 NETs. Even if the growth of the neoplasm was significantly inhibited, it is still unclear whether its antiproliferative action is greater than that of octreotide and lanreotide. Because new therapeutic options are needed to counter the natural behavior of neuroendocrine tumors, it would also be useful to have a biochemical marker that can be addressed better in the management of these patients. Chromogranin A is currently the most useful biomarker to establish diagnosis and has some utility in predicting disease recurrence, outcome, and efficacy of therapy.

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Usefulness of Chest and Skeletal Survey to Assess the Time of Relapse in Breast Cancer

Tumori Journal ◽

10.1177/030089168106700107 ◽

1981 ◽

Vol 67 (1) ◽

pp. 35-38 ◽

Cited By ~ 7

Author(s):

John David Tesoro-Tess ◽

Pinuccia Valagussa ◽

Gianstefano Gardani ◽

Anna Rossi ◽

Gabriele Tancini ◽

...

Keyword(s):

Breast Cancer ◽

Diagnostic Accuracy ◽

Morphological Characteristics ◽

Radical Mastectomy ◽

Retrospective Evaluation ◽

Biochemical Tests ◽

A Value ◽

Asymptomatic Patients ◽

Radiological Report ◽

Chest Examination

The pertinent radiographs of 151 patients treated with radical mastectomy who showed relapse in the chest and/or in the skeleton as first site were reevaluated. Diagnostic accuracy was calculated by comparing the first examination considered as positive with the previous ones reported as negative. For chest lesions the accuracy was 80 % (70 % for parenchymal nodular densities), with no difference between symptomatic and asymptomatic patients. For bone metastases retrospective evaluation confirmed the radiological report (i.e., the time of relapse), in 73.8 %, with a value of 89.7 % in symptomatic and 53.4 % in asymptomatic patients. The site of involvement and morphological characteristics of the lesions did not influence the diagnostic accuracy. Therefore chest examination and, for symptomatic patients, radiographic bone survey still represent a useful modality to assess the diffusion of breast cancer. For asymptomatic patients other modalities, such as bone scan and biochemical tests, should be utilized.

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Molecular and Biochemical Studies of Acute Intermittent Porphyria in 196 Patients and Their Families

Clinical Chemistry ◽

10.1093/clinchem/48.11.1891 ◽

2002 ◽

Vol 48 (11) ◽

pp. 1891-1900 ◽

Cited By ~ 54

Author(s):

Raili Kauppinen ◽

Mikael von und zu Fraunberg

Keyword(s):

Diagnostic Accuracy ◽

Aminolevulinic Acid ◽

Clinical Manifestations ◽

Acute Intermittent Porphyria ◽

Reference Interval ◽

Acute Attack ◽

Fecal Excretion ◽

Variant Form ◽

Roc Curve Analysis ◽

Biochemical Tests

Abstract Background: Acute intermittent porphyria (AIP) is a metabolic disease with clinical manifestations that mimic other abdominal, neurologic, or mental crises. We studied the diagnostic accuracy of current laboratory tests during an acute attack and in remission. Methods: Since 1966, we have studied all known Finnish AIP patients (n = 196) and their families (n = 45) and identified the porphobilinogen deaminase (PBGD) mutation in each family. Diagnoses or exclusions of AIP were based on clinical data (including family history), biochemical tests, and in 239 cases, mutation testing. We retrospectively evaluated the diagnostic accuracy of erythrocyte PBGD activity, urinary excretion of porphobilinogen (PBG) and δ-aminolevulinic acid, and urinary and fecal excretion of porphyrins in these patients. Results: Measurement of urinary PBG identified all 35 AIP patients studied during an acute attack. The mean excretion of PBG was 50-fold above the reference interval, although the intraindividual increases were modest (1.6- to 4.0-fold). In the mutation-screened population, urinary PBG analysis identified only 85% of 81 AIP patients studied during remission, but by ROC curve analysis it was nonetheless the best of the biochemical tests. It was increased ≤2-fold in 29% of healthy relatives. Erythrocyte PBGD activity was decreased in only 84% of AIP patients, with results within the reference interval mainly in the variant form of AIP; it was decreased in 23% of healthy relatives. Conclusions: Measurement of urinary PBG is the best biochemical test for AIP, although it is unspecific and does not distinguish AIP from other acute porphyrias. Because the acute increase in PBG is often modest, the medical history, signs, and symptoms must be evaluated carefully during an acute attack. In addition, because biochemical analyses often remain indeterminate in remission, mutation analysis is needed to exclude or confirm the diagnosis of AIP.

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