Elevated chromogranin A serum levels in ovarian carcinoma patients.

Background: The observation of neuroendocrine activity during clinical course of ovarian cancer, suggested the use of neuroendocrine serum markers to detect this tumor. Aim: To evaluate the usefulness of serum measurements of chromogranin A (CgA) in the various stages of ovarian cancer. Materials and Methods: We measured serum concentrations of CgA and cancer antigen 125 (CA125) in 79 women at different clinical stages of ovarian cancer, enrolled between 2000 and 2007, and in a control group of 50 female volunteers. Results: CgA showed increased levels in patients with ovarian cancer as compared with healthy subjects, as it has been seen for CA125 serum levels. We also observed significant increase in CgA and CA125 serum levels when comparing patients with ovarian cancer in stage I versus stage II (P < 0.001); stage I versus stage III (P < 0.001); stage I versus stage IV (P < 0.001); stage II versus stage III (P < 0.001); stage II versus stage IV (P < 0.001). In patients with ovarian carcinoma in stage IV we observed a correlation between CgA and CA125 with a difference of 0.718 (P < 0.001). Conclusions: CgA serum levels were elevated in ovarian cancer and increased with the stage. Further studies are needed to elucidate the role of CgA as a prognostic indicator during treatment for ovarian cancer.

A Case of Alpha-cell Nesidioblastosis and Hyperplasia with Multiple Glucagon-producing Endocrine Cell Tumor of the Pancreas / 대한소화기학회지

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.

Clinical Usefulness of Plasma Chromogranin A in Pancreatic Neuroendocrine Neoplasm

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.

Diagnostic work-up of gastroenteropancreatic neuroendocrine tumors

Neuroendocrine tumors are a heterogeneous group of malignancies that present a diagnostic challenge. The majority of patients (more than 60%) present with metastatic disease at diagnosis. The diagnosis is based on histopathology, imaging, and circulating biomarkers. The histopathology should contain specific neuroendocrine markers such as chromogranin A, synaptophysin, and neuron-specific enolase and also an estimate of the proliferation by Ki-67 (MIB1). Standard imaging procedures consist of computed tomography or magnetic resonance imaging together with somatostatin receptor scintigraphy. 68Ga-DOTA-octreotate scans will in the future replace somatostatin receptor scintigraphy because they have higher specificity and sensitivity. Other positron imaging tomographic scanning tracers that will come into clinical use are 18F-DOPA and 11C-5HTP. Neuroendocrine tumors secrete many different peptides and amines that can be used as circulating biomarkers. The most useful general marker is chromogranin A, which is both a diagnostic and prognostic marker in most neuroendocrine tumors. However, there is still a need for improved biomarkers for early detection and follow-up of patients during treatment. In addition, molecular imaging can be further developed for both detection and evaluation of treatment.

Influence of Long-term Gastric Acid Suppression Therapy on the Expression of Serum Gastrin, Chromogranin A, and Ghrelin / 대한소화기학회지

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.

Influence of Long-term Gastric Acid Suppression Therapy on the Expression of Serum Gastrin, Chromogranin A, and Ghrelin / 대한소화기학회지

No abstract available.