gastrins and Digestive-System-Neoplasms

Topics: Cholecystokinin; Digestive System; Digestive System Neoplasms; Gastrins; Humans

Serum gastrin levels exceeding 1000pg/ml (normal, <100) usually raise the suspicion for a neuroendocrine tumor (NET) that secretes gastrin. Rarely, such elevated gastrin levels are seen in patients with pernicious anemia which most commonly is associated with autoimmune gastritis (AG). AG can occur concomitantly with other autoimmune disorders including lymphocytic colitis (LC). Gastrin stimulates enterochromaffin-like cells which increase histamine secretion. Histamine excess can cause diarrhea as can bacterial overgrowth or LC. We present a 57-year-old woman with diarrhea, sporadic epigastric pain, and bloating. She also had a history of interstitial cystitis and took pentosan polysulfate and cetirizine. She had no history of ulcers, renal impairment or carcinoid syndrome. Fasting serum gastrin was 1846pg/ml. Esophagoduodenal gastroscopy and biopsies revealed chronic gastritis and a pH of 7 with low stomach acid. Serum gastrin and plasma chromogranin A were suggestive of a gastrinoma or NET. Pernicious anemia was unlikely. Imaging studies did not reveal any tumor. Random colonic biopsy was compatible with LC, possibly explaining her diarrhea, although we also considered excessive histamine from elevated gastrin, bacterial overgrowth, and pentosan polysulfate which can cause diarrhea and be misleading in this setting, pointing to the diagnosis of gastrinoma. At 4year follow-up in 2012, fasting serum gastrin was 1097pg/ml and the patient asymptomatic taking only cetirizine for nasal allergies. This case illustrates that diarrhea may be associated with very high serum gastrin levels in the setting of chronic gastritis, LC, and interstitial cystitis (pentosan use), without clear evidence for a gastrinoma or NET. If no history of ulcers or liver metastases is present in such cases, watchful observation rather than an extensive/invasive and costly search for a NET may be justified. Considering the various forms of polyglandular syndrome, this may represent a variant and we here provide an algorithm for working up such patients, while also reviewing literature on the intertwined relationship between the immune and endocrine systems.

Topics: Autoimmune Diseases; Chronic Disease; Colitis, Lymphocytic; Diagnosis, Differential; Digestive System Neoplasms; Female; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Middle Aged; Neuroendocrine Tumors

In gastrinomas, as well as in other endocrine tumors whose hormone overproduction is responsible for clinical syndromes, antibodies against the bioactive form(s) of hormones can fail to detect immunoreactivity. Moreover, tumor secretory granule morphology may fail to allow tumor type identification. The use of anti-pre-pro-gastrin antibodies has been proposed as an alternative to identify gastrinomas. The aim of the present study was to demonstrate that in situ detection of gastrin mRNA may represent another possibility. A 35S-labeled cDNA probe encoding the human gastrin pre-pro-hormone was used to localize gastrin gene transcripts in antral mucosa and digestive endocrine tumors from patients with a Zollinger-Ellison syndrome characterized by high serum gastrin levels. In situ hybridization was combined with light and electron microscopic immunostaining of the bioactive gastrin 17/34 form and morphological study of secretory granules. Gastrin mRNAs were detected in antral gastrin cells and in a variable proportion of tumor cells in all endocrine tumor studied. Transcript expression correlated well with immunohistochemical staining and granule ultrastructure for most of the tumors, and provided crucial evidence for identifying as gastrinomas two tumors with weak immunoreactivity and poorly granulated cells. Our data show that in situ hybridization is a sensitive method for gastrin mRNA detection and represents a valuable tool for the identification of gastrinomas.

Topics: Digestive System Neoplasms; Endocrine Gland Neoplasms; Gastric Mucosa; Gastrins; Humans; Immunohistochemistry; Lymph Nodes; Lymphatic Metastasis; Microscopy, Electron; Nucleic Acid Hybridization; RNA, Messenger; Tissue Fixation; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Digestive System Neoplasms; Female; Gastrinoma; Gastrins; Humans; Mesenteric Vascular Occlusion; Middle Aged; Radiography; Secretin

The changes in gastric acid secretion and gut hormone release were investigated in 11 patients who underwent pancreaticoduodenectomy. The amount of acid output showed normoacidity before surgery and hypoacidity after surgery. No peptic ulcers were detectable after surgery. Plasma gastrin levels were markedly reduced after surgery both in the fasting state and after a test meal loading. Although fasting plasma levels of both gastric inhibitory polypeptide (GIP) and insulin after surgery were close to those before surgery, the response of these hormones to the meal was significantly reduced after surgery. On the other hand, blood glucose concentrations increased gradually after feeding, and the elevation was greatly prolonged after surgery compared with preoperative levels. From these results, it is concluded that peptic ulcer will not occur if subtotal gastrectomy is performed during Whipple's procedure. It is presumed that the diminished release of gut hormones such as gastrin, GIP, and insulin was due to the massive resection of the distal stomach, the upper small intestine, and the head of the pancreas and to the diversion of the stream of food from the duodenum to the jejunum. It is also assumed that the glucose-dependent insulinotropic action of GIP would be impaired by the procedure.

Topics: Adult; Aged; Blood Glucose; Digestive System Neoplasms; Duodenum; Eating; Female; Gastrectomy; Gastric Acid; Gastric Acidity Determination; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Jejunum; Male; Middle Aged; Pancreas; Pancreatic Ducts