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

Multiple endocrine neoplasia (MEN) mutation is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. The incidence of insulinoma in MEN is relatively uncommon, and there have been a few cases of MEN manifested with insulinoma as the first symptom in children. We experienced a 9-year-old girl having a familial MEN1 mutation. She complained of dizziness, occasional palpitation, weakness, hunger, sweating, and generalized tonic-clonic seizure that lasted for 5 minutes early in the morning. At first, she was only diagnosed with insulinoma by abdominal magnetic resonance images of a 1.3 × 1.5 cm mass in the pancreas and high insulin levels in blood of the hepatic vein, but after her father was diagnosed with MEN1. We found she had familial MEN1 mutation, and she recovered hyperinsulinemic hypoglycemia after enucleation of the mass. Therefore, the early genetic identification of MEN1 mutation is considerable for children with at least one manifestation.
Alleles ; Base Sequence ; Child ; DNA Mutational Analysis ; Female ; Humans ; Hypoglycemia/diagnosis ; Insulin/blood ; Insulinoma/diagnostic imaging/*pathology ; Magnetic Resonance Imaging ; Multiple Endocrine Neoplasia Type 1/*diagnosis/pathology ; Pancreatic Neoplasms/diagnostic imaging/*pathology ; Pedigree ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins/genetics ; Seizures/complications

OBJECTIVETo find the potential serum specific miRNAs with diagnostic value in early pancreatic cancer and study the alteration of miRNAs levels in the process of origin and development of pancreatic cancer and discuss the diagnostic value of miRNAs in early pancreatic cancer.

METHODSDMBA-induced rat model was established. The miRNAs expression profile of early stage was screened out by microarray. And confirmation study was performed.

RESULTSThe 35 and 12 abnormally expressed miRNAs were acquired in pancreatic tissue and blood respectively. There were no significant differences between normal pancreas and pancreatic cancer in expressions of hsa-let-7c, hsa-miR-122-5p, hsa-miR-142-5p, hsa-miR-199a-3p and hsa-miR-451a (P > 0.05).

CONCLUSIONSmiRNAs are the potential biomarkers of early pancreatic cancer. The establishment of the miRNAs expression profile has build the foundation of exploring the molecular mechanism of origin of pancreatic cancer.

Animals ; Biomarkers, Tumor ; blood ; metabolism ; Disease Models, Animal ; Male ; MicroRNAs ; blood ; metabolism ; Pancreas ; metabolism ; Pancreatic Neoplasms ; diagnosis ; genetics ; Prognosis ; Rats ; Rats, Sprague-Dawley ; Transcriptome

Herein, we report the case of a large benign insulinoma in an obese young man with a three-year history of asymptomatic hypoglycaemia. He presented to our outpatient department with a two-week history of dizziness and morning cold sweats. A random serum glucose test revealed hypoglycaemia. Upon admission, computed tomography and magnetic resonance imaging of the abdomen with intravenous contrast media showed an enhancing mass lesion in the uncinate process of the pancreas. To confirm the diagnosis, an intra-arterial calcium stimulation test with hepatic venous sampling was performed for preoperative localisation and to exclude the presence of occult insulinomas. The patient underwent an exploratory laparotomy, with successful resection of the pancreatic head tumour. Histology confirmed the diagnosis of insulinoma. The patient's postoperative recovery was uneventful, and he has not developed further episodes of hypoglycaemia three years post surgery.
Adult ; Blood Glucose ; analysis ; Calcium ; metabolism ; Contrast Media ; chemistry ; Hepatic Veins ; pathology ; Humans ; Insulinoma ; blood ; complications ; diagnosis ; Magnetic Resonance Imaging ; Male ; Obesity ; blood ; complications ; Pancreatic Neoplasms ; blood ; complications ; diagnosis ; Tomography, X-Ray Computed

BACKGROUND/AIMS: The prognosis of pancreatic adenocarcinoma (PAC) is poor. The serum carbohydrate antigen 19-9 (CA 19-9) level has been identified as a prognostic indicator of recurrence and reduced overall survival. The aim of this study was to identify preoperative prognostic factors and to create a prognostic model able to assess the early recurrence risk for patients with resectable PAC. METHODS: A series of 177 patients with PAC treated surgically at the St. Andrea Hospital of Rome between January 2003 and December 2011 were reviewed retrospectively. Univariate and multivariate analyses were utilized to identify preoperative prognostic indicators. RESULTS: A preoperative CA 19-9 level >228 U/mL, tumor size >3.1 cm, and the presence of pathological preoperative lymph nodes statistically correlated with early recurrence. Together, these three factors predicted the possibility of an early recurrence with 90.4% accuracy. The combination of these three preoperative conditions was identified as an independent parameter for early recurrence based on multivariate analysis (p=0.0314; hazard ratio, 3.9811; 95% confidence interval, 1.1745 to 15.3245). CONCLUSIONS: PAC patient candidates for surgical resection should undergo an assessment of early recurrence risk to avoid unnecessary and ineffective resection and to identify patients for whom palliative or alternative treatment may be the treatment of choice.
Adenocarcinoma/*diagnosis/surgery ; Aged ; CA-19-9 Antigen/blood ; Feasibility Studies ; Female ; Humans ; Male ; *Models, Biological ; Neoplasm Recurrence, Local/*diagnosis ; Pancreatic Neoplasms/*diagnosis/surgery ; Prognosis ; Retrospective Studies ; Tumor Markers, Biological/*blood

OBJECTIVEThe aim of this study was to identify six miRNAs expressed in plasma of patients with pancreatic cancer (PCa) and analyze their value as a diagnostic index of pancreatic cancer.

METHODSPlasma total RNAs were extracted from 30 PCa patients and 26 normal controls, and the abundance of six microRNAs was measured using real-time PCR. The possibility to combine them with CA19-9 as diagnostic biomarkers was analyzed.

RESULTSThe expression level of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a in plasma of patients with pancreatic cancer were 1.65×10(6), 5.98×10(4), 2.83×10(3), 3.47×10(6), 2.76×10(6), and 1.03×10(3) (copies/µl), while the normal controls were 4.08×10(5), 2.54×10(4), 8.55×10(2), 1.79×10(6), 9.32×10(5), and 4.67×10(2) (copies/µl), respectively, with a significant difference between the two groups (P < 0.05). The areas under the ROC curve of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a were 0.893, 0.810, 0.820, 0.766, 0.816 and 0.729, respectively. MiR-21 had the highest diagnostic value when it was used as diagnostic marker alone. The combination of miR-155 and miR-25 was more effective to distinguish PCa from normal than to be used alone, and the area under the ROC curve was 0.913 (95%CI 0.838-0.988) .When CA199 associated with miR -210 and miR-25, respectively, the areas under the ROC curves were 0.96 (95%CI was 0-1.0) and 0.942 (95% CI was 0.876-1.0), which were higher than CA199 alone (0.862, 95%CI was 0.748-0.975). There was a high improvement in diagnostic sensitivity and accuracy when miR-210 and miR-25 were combined with CA19-9, respectively.

CONCLUSIONSPlasma miR-21, miR-155, miR-25, miR-210 have diagnostic value for pancreatic cancer, and deserve further study.

Aged ; Biomarkers, Tumor ; blood ; genetics ; CA-19-9 Antigen ; blood ; Case-Control Studies ; Female ; Humans ; Male ; MicroRNAs ; blood ; Middle Aged ; Pancreatic Neoplasms ; blood ; diagnosis ; genetics ; ROC Curve ; Real-Time Polymerase Chain Reaction

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

Several studies have reported that ABO blood group, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection contribute to the development of pancreatic cancer. The aim of this study was to evaluate the association between these factors and pancreatic cancer in the Korean population. We retrospectively recruited 753 patients with pancreatic cancer and 3,012 healthy controls, matched 4 to 1 with cancer patients for age and sex, between 2001 and 2011, at the National Cancer Center, Korea. A multivariate logistic regression analysis was employed to estimate adjusted odds ratios (AORs). The AOR for pancreatic cancer in subjects with non-O blood types (A, AB, and B), compared to blood type O, was 1.29 (95% CI, 1.05-1.58; P = 0.01). Seropositivity for hepatitis B virus surface antigen was not significantly related to pancreatic cancer, either in univariate (odds ratio 1.03; 95% CI, 0.69-1.53; P = 0.91) or multivariate analysis (AOR, 1.02; 95% CI, 0.67-1.56; P = 0.93). The AOR for pancreatic cancer in subjects displaying seropositivity for anti-HCV was 2.30 (95% CI, 1.30-4.08; P < 0.01). Our results suggest that the non-O blood types and anti-HCV seropositivity, but not HBV infection, may increase the risk of developing pancreatic cancer in Korea, where HBV is endemic.
ABO Blood-Group System ; Aged ; Case-Control Studies ; Female ; Hepatitis B/complications/diagnosis ; Hepatitis B Surface Antigens/blood ; Hepatitis C/*complications/diagnosis ; Hepatitis C Antibodies/blood ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Pancreatic Neoplasms/diagnosis/*etiology ; Republic of Korea ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: Autoimmune pancreatitis (AIP) often occurs with obstructive jaundice in old age in cases of weight loss, mimicking pancreatobiliary cancer. This study aimed to determine the sensitivity and specificity serum IgG, IgG4 and CEA, CA 19-9 levels for the diagnosis of AIP and their ability to distinguish AIP from pancreatobiliary cancer. METHODS: The level of serums IgG, IgG4 and CEA, CA 19-9 were measured in 413 patients including 125 with AIP, 201 with pancreatic cancer, and 87 with cholangiocarcinoma. RESULTS: Among AIP patients, 43.2% (54/125) showed elevated IgG levels (> or =1,800 mg/dL) and 52% (65/125) showed elevated IgG4 levels (> or =135 mg/dL). Sensitivity and specificity of elevated serum IgG for diagnosis AIP were 43% and 88% respectively, and 52% and 97%, respectively for elevated serum IgG4. When the cut-off value of serum IgG4 was raised to 270 mg/dL (twice the upper limit of normal), the specificity improved to 100%. About 25% of the AIP patients showed an increased level of CA 19-9 at >37 U/mL and about 12.2% of them showed an increased level of CA 19-9 at >100 U/mL. On the contrary, only 1.8% of the AIP patients showed an increased level of CEA at >6.0 ng/mL. CONCLUSIONS: To avoid unnecessary surgeries resulting from a misdiagnosed pancreatobiliary cancer as opposed to AIP, it is necessary to consider both serum immunoglobulin and tumor marker. In particular, because high level of IgG4 (> or =270 mg/dL) and CA19-9 (>100 U/mL) are relatively rare in pancreatobiliary cancer and AIP, respectively, they will be helpful in differential diagnosis.
Adult ; Aged ; Autoimmune Diseases/blood/*diagnosis ; CA-19-9 Antigen/blood ; Carcinoembryonic Antigen/blood ; Cholangiocarcinoma/blood/diagnosis ; Diagnostic Errors ; Female ; Humans ; Immunoglobulin G/blood ; Male ; Middle Aged ; Pancreatic Neoplasms/blood/*diagnosis ; Pancreatitis, Chronic/blood/*diagnosis ; ROC Curve ; Tumor Markers, Biological/*blood

No abstract available.
Autoimmune Diseases/*diagnosis ; Female ; Humans ; Male ; Pancreatic Neoplasms/*diagnosis ; Pancreatitis, Chronic/*diagnosis ; Tumor Markers, Biological/*blood