gastrins and Zollinger-Ellison-Syndrome

Zollinger-Ellison syndrome (ZES) is a distinct syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea. It is the result of a gastrin-excess state caused by a duodenal or pancreatic neuroendocrine tumor referred to as gastrinoma. This gastrin-secreting neuroendocrine tumor is usually sporadic in nature, or part of multiple endocrine neoplasia type 1 syndrome. The high rate of malignancy associated with gastrinomas substantiates the need for early diagnosis. In order to diagnose ZES with laboratory tests, patients under antacid medication are required to stay off proton pump inhibitors for at least one week and H2 receptor antagonists for 48 h. Fasting serum gastrin level measurement serves as an initial and fundamental diagnostic test, boasting a sensitivity of 99%. Gastrinoma patients will present with a gastrin level greater than 100 pg/mL, while a serum gastrin level higher than 1000 pg/mL, in the presence of gastric pH <2, is considered diagnostic. Since more common causes of hypergastrinemia exist in the setting of hypochlorhydria, ruling those out should precede ZES consideration. Such causes include atrophic gastritis, Helicobacter pylori (H. pylori)-associated pangastritis, renal failure, vagotomy, gastric outlet obstruction and retained antrum syndrome. The secretin stimulation test and the calcium gluconate injection test represent classic adjuvant diagnostic techniques, while alternative approaches are currently being introduced and evaluated. Specifically, the secretin stimulation test aids in differentiating ZES cases from other hypergastrinemic states. Its principle is based on secretin stimulation of gastrinoma cells to secrete gastrin, while inhibiting normal G cells. The rapid intravenous infusion of 4 μg/kg secretin over 1 min is followed by gastrin level evaluation at specific intervals post-infusion. Localization of the primary tumor and its metastases is the next diagnostic step when gastrinoma-associated ZES is either suspected or biochemically confirmed. Endoscopic ultrasound has showcased sensitivity as high as 83% for pancreatic gastrinomas and is considered the primary modality in such cases, although its tumor detection rates are substantially lower in duodenal lesions. Gallium-68 radiotracers, especially DOTATOC with positron emission tomography, are currently setting the standard in tumor localization, enhancing traditional imaging techniques and showcasing high sensitivity and specificity.

Topics: Gastrinoma; Gastrins; Humans; Multiple Endocrine Neoplasia Type 1; Proton Pump Inhibitors; Secretin; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is characterized by gastric acid hypersecretion causing severe recurrent acid-related peptic disease. Excessive secretion of gastrin can now be effectively controlled with powerful proton pump inhibitors, but surgical management to control gastrinoma itself remains controversial. Based on a thorough literature review, we design a surgical algorithm for ZES and list some significant consensus findings and recommendations: (1) For sporadic ZES, surgery should be routinely undertaken as early as possible not only for patients with a precisely localized diagnosis but also for those with negative imaging findings. The surgical approach for sporadic ZES depends on the lesion location (including the duodenum, pancreas, lymph nodes, hepatobiliary tract, stomach, and some extremely rare sites such as the ovaries, heart, omentum, and jejunum). Intraoperative liver exploration and lymphadenectomy should be routinely performed; (2) For multiple endocrine neoplasia type 1-related ZES (MEN1/ZES), surgery should not be performed routinely except for lesions > 2 cm. An attempt to perform radical resection (pancreaticoduodenectomy followed by lymphadenectomy) can be made. The ameliorating effect of parathyroid surgery should be considered, and parathyroidectomy should be performed first before any abdominal surgery for ZES; and (3) For hepatic metastatic disease, hepatic resection should be routinely performed. Currently, liver transplantation is still considered an investigational therapeutic approach for ZES. Well-designed prospective studies are desperately needed to further verify and modify the current considerations.

Topics: Duodenum; Gastrin-Secreting Cells; Gastrins; Gastroenterology; Hepatectomy; Humans; Liver; Lymph Node Excision; Medical Oncology; Pancreas; Pancreaticoduodenectomy; Parathyroidectomy; Practice Guidelines as Topic; Stomach; Time Factors; Zollinger-Ellison Syndrome

The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.

Topics: Animals; Carcinoma, Neuroendocrine; Chronic Disease; Gastrinoma; Gastrins; Humans; Proton Pump Inhibitors; Risk Factors; Stomach Diseases; Time Factors; Treatment Outcome; Zollinger-Ellison Syndrome

Gastrin measurements are performed primarily for the diagnosis of gastrin-producing tumors, gastrinomas, which cause the Zollinger-Ellison syndrome (ZES). Gastrin circulates as several bioactive peptides, however, and the peptide pattern in gastrinoma patients often deviates from normal. Therefore, it is necessary to measure all forms of gastrin.. Only immunoassays are useful for measurement of gastrin in plasma. The original assays were RIAs developed in research laboratories that used antibodies directed against the C terminus of gastrin peptides. Because the C-terminal tetrapeptide amide sequence constitutes the active site of gastrin peptides, these assays were well suited for gastrinoma diagnosis. More recently, however, most clinical chemistry laboratories have switched to commercial kits. Because of recent cases of kit-measured normogastrinemia in patients with ZES symptoms, the diagnostic sensitivity and analytical specificity of the available kits have been examined. The results show that gastrin kits frequently measure falsely low concentrations because they measure only a single gastrin form. Falsely high concentrations were also encountered, owing to overreactivity with O-sulfated gastrins or plasma proteins. Thus, more than half of the gastrin kits on the market are unsuited for diagnostics.. Gastrinomas are neuroendocrine tumors, some of which become malignant. A delay in diagnosis leads to fulminant ZES, with major, even lethal, complications. Consequently, it is necessary that the diagnostic sensitivity of gastrin kits be adequate. This diagnostic sensitivity requires antibodies that bind the C-terminal epitope of bioactive gastrins without the influence of O-sulfation.

Topics: Amino Acid Sequence; Antibody Specificity; Biomarkers, Tumor; Gastrinoma; Gastrins; Humans; Immunoassay; Molecular Sequence Data; Reagent Kits, Diagnostic; Sensitivity and Specificity; Zollinger-Ellison Syndrome

In the present paper the increasing difficulty of diagnosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the perspective of clinical management.

Topics: Contraindications; Gastrins; Humans; Proton Pump Inhibitors; Zollinger-Ellison Syndrome

Topics: Anti-Ulcer Agents; Duodenum; Gastric Acid; Gastrins; Humans; Parietal Cells, Gastric; Proton Pump Inhibitors; Proton Pumps; Treatment Outcome; Zollinger-Ellison Syndrome

Topics: Aged; Calcium; Child; Gastrinoma; Gastrins; History, 20th Century; Humans; Pancreatic Neoplasms; Prognosis; Secretin; Zollinger-Ellison Syndrome

In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffin cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia, such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.

Topics: Adenocarcinoma; Animals; Cell Movement; Cell Proliferation; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Humans; Mice; Mice, Transgenic; Models, Biological; Neoplasm Invasiveness; Neovascularization, Pathologic; Neuroendocrine Tumors; Stomach Neoplasms; Zollinger-Ellison Syndrome

As there is considerable overlap between the fasting serum gastrin concentrations found in Zollinger-Ellison syndrome and various common conditions such as Helicobacter pylori infection and acid suppressing medication use, establishing the cause of hypergastrinaemia in individual cases can sometimes be difficult.. To review the causes of hypergastrinaemia and the role of additional non-invasive investigations in hypergastrinaemic patients.. Review of articles following a Pubmed search.. As gastrinomas may cause serious complications and be potentially life threatening, investigation of hypergastrinaemic patients should particularly focus on confirming or refuting the diagnosis of Zollinger-Ellison syndrome. Establishing the cause of hypergastrinaemia may be difficult when there is only a mild-to-moderate elevation of fasting serum gastrin concentration and concurrent treatment with proton pump inhibitor drugs and the presence of H. pylori infection can both confuse the clinical picture. A variety of provocative tests are therefore useful for establishing whether a hypergastrinaemic patient has a gastrinoma and current evidence suggests that the secretin test should be used first line.. We suggest an algorithm for the investigation of patients found to have an elevated fasting serum gastrin concentration and address the roles of gastrin stimulation tests in current clinical practice.

Topics: Algorithms; Diagnosis, Differential; Gastrinoma; Gastrins; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Secretin; Zollinger-Ellison Syndrome

Gastric acid hypersecretory states are characterized by basal hypersecretion of gastric acid and historically include disorders associated with hypergastrinemia, hyperhistaminemia, and those of unknown etiology. Although gastric acid secretion is infrequently measured, it is important to recognize the role of gastric hypersecretion in the symptoms of these disorders because they share several features of pathogenesis and treatment. In this article, recent important articles reporting insights into their diagnosis, pathogenesis, and treatment are reviewed. Particular attention is paid to Zollinger-Ellison syndrome, because it has the most extreme acid hypersecretion of this group of disorders and because numerous recent articles deal with various aspects of the diagnosis, molecular pathogenesis, and treatment of the gastrinoma itself or the acid hypersecretion. Two new hypersecretory disorders are reviewed: rebound acid hypersecretion after the use of proton pump inhibitors and acid hypersecretion with cysteamine treatment in children with cystinosis.

Topics: Cystamine; Cystinosis; Enzyme Inhibitors; Gastric Acid; Gastrins; Histamine; Humans; Proton Pump Inhibitors; Stomach Diseases; Zollinger-Ellison Syndrome

The odyssey of Zollinger-Ellison Syndrome is one of the most interesting in surgery. From the initial recognition of two patients with severe peptic ulcer disease in 1955 sprung an international dialogue on this unique disease culminating in discovery that gastrin was the hormone secreted by these pancreatic and duodenal tumors. The impact was the birth of a new area of science, "gastrointestinal endocrinology." Initially, surgeons were challenged by the complexity of the patients and the need to perform total gastrectomy to prevent death from complications of the severe ulcer disease. Later, after the discovery of proton pump inhibitors, total gastrectomy was no longer needed and the surgeon could focus treatment on tumor removal added by radioimmunoassay for gastrin and new imaging modalities. Today, we recognize that all gastrinomas have malignant potential; early surgical removal can reduce the incidence of metastases and improve survival, independent of biochemical cure, in both sporadic and familial forms of the disease.

Topics: Biomarkers, Tumor; Diagnosis, Differential; Diagnostic Imaging; Gastrectomy; Gastrins; Global Health; Humans; Prognosis; Proton Pump Inhibitors; Radioimmunoassay; Survival Rate; Zollinger-Ellison Syndrome

A 61-year-old woman was referred to our hospital for a double balloon endoscopy (DBE) examination of small intestine. She had undergone laparotomy for a perforated ulcer of the 3rd portion in the duodenum 3 years prior to this admission. Esophagogastroduodenoscopy at the previous hospital revealed multiple ulcers in the 2nd and 3rd portions in the duodenum. DBE revealed multiple ulcer scars in the proximal jejunum. Zollinger-Ellison syndrome was suspected from the distribution of the ulcers and scars. Serum gastrin was high and a selective arterial calcium injection test showed a step up of gastrin level only in the gastroduodenal artery area. We diagnosed a gastrinoma located on the ventral side of the 2nd portion of the duodenum from imaging studies. The tumor was extirpated and histologically found to be a neuroendocrine tumor in a lymph node. Serum gastrin level decreased to the normal range a day after surgery.

Topics: Biomarkers, Tumor; Diagnostic Imaging; Duodenal Ulcer; Endoscopy, Digestive System; Female; Gastrins; Humans; Middle Aged; Peptic Ulcer Perforation; Time Factors; Zollinger-Ellison Syndrome

The hormone gastrin plays 2 important roles in gastrointestinal physiology--1 as a major factor in meal-stimulated gastric acid secretion and the other as a trophic hormone for epithelial and enterochromaffin cells. These roles are exaggerated to the point of pathology under conditions of chronic hypergastrinemia as exemplified by the Zollinger-Ellison syndrome and pernicious anemia. More recently, the concern about the potential risk of chronic hypergastrinemia has risen because of the widespread use of proton pump inhibitors for maintenance therapy in reflux esophagitis. For this reason, we present a concise overview of the origin, causes, and potential risks of chronic hypergastrinemia.

Topics: Animals; Enzyme Inhibitors; Gastric Acid; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Peptic Ulcer; Proton Pump Inhibitors; Risk Factors; Zollinger-Ellison Syndrome

The most frequent conditions of hypergastrinemia in man are the Zollinger-Ellison syndrome with autonomous gastrin hypersecretion by the tumour cell and reactive hypergastrinemia in type A autoimmune chronic atrophic gastritis with achlorhydria causing unrestrained gastrin release from the gastrin-producing antral G-cells. Both entities differ with respect to the pH in the gastric fluid, which is < 2 in patients with Zollinger-Ellison syndrome and neutral in type A gastritis. Other conditions with moderate hypergastrinemia as treatment with proton pump inhibitors, gastric outlet obstruction, previous vagotomy, chronic renal failure or short bowel syndrome are of minor clinical importance.

Topics: Autoimmune Diseases; Carcinoid Tumor; Diagnosis, Differential; Duodenal Neoplasms; Enterochromaffin-like Cells; Gastric Mucosa; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Hyperplasia; Pancreatic Neoplasms; Stomach Neoplasms; Zollinger-Ellison Syndrome

Gastrinomas are defined as gastrin producing tumors that are associated with an elevated fasting gastrin serum level, a positive gastrin secretin stimulation test and certain clinical symptoms, e.g. recurrent peptic ulcer disease and occasionally diarrhea, the so-called Zollinger-Ellison syndrome. Most gastrinomas occur in the duodenum (approx. 70%) and not in the pancreas. The duodenal gastrinomas are small, and when they occur in association with the genetic syndrome of multiple endocrine neoplasia type 1 (MEN1), they are multicentric and originate from precursor lesions. The prognosis of duodenal gastrinomas is better than that of pancreatic gastrinomas, since despite early lymph node metastasis they progress slowly to liver metastasis.

Topics: Duodenal Neoplasms; Duodenum; Gastrin-Secreting Cells; Gastrinoma; Gastrins; Humans; Hyperplasia; Multiple Endocrine Neoplasia Type 1; Pancreas; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Cross sectional imaging in the assessment of gastrinomas has three major applications: Tumor localization (sporadic gastrinoma, MEN I) in patients undergoing primary or secondary surgery. Staging of metastasized tumors, especially assessment of lymph nodes and liver metastases, possibly including a risk analysis prior to liver resection. Post-surgery follow-up and monitoring of bio- or chemotherapy. Detection of primary tumors is strongly correlated with their size. However, the sensitivity of surgical assessment of the mostly small tumors by experienced surgeons is much higher than that of any imaging modality. Of all imaging modalities, endoultrasonography (EUS) followed by Somatostatin receptor scintigraphy (SRS) is the most sensitive modality for the assessment of pancreatic tumors in asymptomatic patients suffering from a MEN-I syndrome. Scintigraphy has the highest sensitivity in tumors of symptomatic patients and in the assessment of metastases. CT and MRI are only second line diagnostic modalities. Their sensitivity is largely dependent on the selection of patients. As a potential application, 3D reconstruction of nearly isotropic CT data sets for the risk assessment prior to liver resection is currently developing. Due to the absent radiation exposure, MRI is increasingly utilized to monitor the response of metastases under systemic therapy, e.g. in clinical trials.

Topics: Angiography; Clinical Trials as Topic; Duodenal Neoplasms; Duodenum; Gastrinoma; Gastrins; Humans; Liver; Liver Neoplasms; Lymphatic Metastasis; Magnetic Resonance Imaging; Multiple Endocrine Neoplasia Type 1; Neoplasm Staging; Pancreas; Pancreatic Neoplasms; Tomography, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

Gastrinoma is the most frequent functional pancreaticoduodenal endocrine tumor in patients with multiple endocrine neoplasia type 1 (MEN1) and one major determinant of mortality in this syndrome. Whether routine surgical exploration should be performed in a patient with MEN1 associated Zollinger-Ellison syndrome (ZES) to possibly reduce the malignant spread and eventually increase survival still remains controversial. There is not only disagreement about the indication for surgical exploration, but also what type of procedure should be performed, since sufficient evidence-based data are not available. The article discusses the available data on treatment strategies of MEN1 associated ZES.

Topics: Disease Progression; Duodenal Neoplasms; Gastrinoma; Gastrins; Humans; Laparoscopy; Multiple Endocrine Neoplasia Type 1; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Prognosis; Reoperation; Survival Rate; Zollinger-Ellison Syndrome

Surgical therapy for sporadic gastrinoma profits from innovative pre- and intraoperative diagnostics. Preoperative gastrinoma localization is enhanced by sophisticated endoscopic ultrasonography, scintigraphic and arteriographic studies with hormone sampling. Thereby a concise surgical approach is guided and additional intraoperative control of success may be gained by endoscopic transillumination and measurement of stimulated gastrin levels.

Topics: Diagnostic Imaging; Duodenal Neoplasms; Gastrinoma; Gastrins; Humans; Intraoperative Period; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Prognosis; Transillumination; Zollinger-Ellison Syndrome

Gastrinomas are functional neuroendocrine tumors of the gastroenteropancreatic system. Surgery is first line treatment in gastrinomas, however often fails to be curative. This manuscript reviews current strategies of medical treatment of surgically non-curable gastrinoma. Symptomatic treatment with H(+)-K(+)-ATPase proton-pump inhibitors suppresses hypersecretion of gastric acid and substantially improves quality of life in patients with Zollinger-Ellison syndrome. Further medical therapy is only recommended in cases of progressive metastatic gastrinoma. In well differentiated neuroendocrine carcinoma (G1 and G2) a so-called biotherapy with somatostatin analogues exists as first-line and chemotherapy with streptocotozin plus doxorubicine/5-FU as second-line medical treatment option. In poorly differentiated neuroendocrine carcinoma (G3) chemotherapy with etoposide plus cisplatin is possible. Prospective future therapeutic strategies may include treatment with novel somatostatin analogues as well as angiogenesis inhibitors and kinase inhibitors targeting tumor-specific signaling cascades.

Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Duodenal Neoplasms; Gastrinoma; Gastrins; Humans; Interferon-alpha; Octreotide; Pancreatic Neoplasms; Peptides, Cyclic; Proton Pump Inhibitors; Somatostatin; Zollinger-Ellison Syndrome

Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., >10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of >5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed.

Topics: Animals; Carcinoid Tumor; Cell Transformation, Neoplastic; Drug Tolerance; Enterochromaffin-like Cells; Gastric Acid; Gastric Mucosa; Gastrinoma; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Agents; Helicobacter pylori; Humans; Malabsorption Syndromes; Peptic Ulcer; Proton Pump Inhibitors; Stomach Neoplasms; Time Factors; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is characterised by peptic ulcers of the upper gastrointestinal tract failing to heal despite maximal medical therapy, diarrhoea and marked gastric acid hypersecretion associated with a gastrin-secreting tumour (gastrinoma). ZES might be associated with multiple endocrine neoplasia type 1. The main diagnostic features are hypergastrinemia and acid hypersecretion. When these parameters give borderline results, provocation test (with secretin or calcium) may be required. To identify the localisation of gastrinoma several imaging techniques have been proposed. Somatostatin receptor scintigraphy is capable to localise the tumour in 80% of the cases and to identify it even in anatomic sites other than pancreas and duodenum. Endoscopic ultrasonography has a sensitivity as high as 79-93% and a specificity of 93%. The 2 main principal therapeutic strategies are to control both the gastric acid hypersecretion and the growth of the neoplasia. Proton pump inhibitors (PPIs) are the drugs of choice for patients with ZES. Furthermore, safety of PPIs in the maintenance therapy has been proven both in short- and in long-term studies. The best surgical treatment is excision of gastrinoma before metastatic spread has occurred. Somatostatin-analogues can reduce both gastric acid hypersecretion and serum gastrin levels. Moreover, they have an antiproliferative effect. Chemotherapy, interferon and embolisation are indicated in rapidly evolving tumours or in cases in which the tumoral symptoms cannot be treated by other approaches.

Topics: Antineoplastic Agents; Embolization, Therapeutic; Gastric Acid; Gastrinoma; Gastrins; Humans; Interferons; Prognosis; Proton Pump Inhibitors; Somatostatin; Zollinger-Ellison Syndrome

The physiologic sequelae of a gastrinoma can be well controlled with medical therapy. The role of surgery has shifted from managing acid hyper-secretion and ulcer complications to preventing metastatic disease and managing symptomatic metastases. With improved methods of imaging for the detection of occult gastrinomas, the prospective evaluation of the role for surgery in altering the natural history of these tumors is now possible.

Topics: Algorithms; Diagnosis, Differential; Disease-Free Survival; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Sensitivity and Specificity; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Gastrinomas are defined as gastrin secreting tumors that are associated with Zollinger-Ellison syndrome (ZES). ZES is characterized by elevated fasting gastrin serum levels, positive secretin stimulation test and clinical symptoms such as recurrent peptic ulcer disease, gastroesophageal reflux disease and occasional diarrhea. Genetically, nonhereditary (sporadic) gastrinomas are distinguished from hereditary gastrinomas, which are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. In general, duodenal gastrinomas are small and solitary if they are sporadic and multiple as well as hereditary. The sporadic gastrinomas occur in the duodenum or in the pancreas while the hereditary gastrinomas almost all occur in the duodenum. Our series of 77 sporadic duodenal neuroendocrine tumors (NETs) includes 18 patients (23.4%) with gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET archives of the departments of pathology in Zurich, Switzerland, and Kiel, Germany, 24 patients (4.5%) suffered from sporadic pancreatic gastrinomas and ZES. These NETs have to be distinguished from tumors with immunohistochemical positivity for gastrin but without evidence of ZES. An additional 19 patients suffered from MEN1 and ZES. These patients showed exclusively duodenal gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1-associated duodenal gastrinomas is better than that of pancreatic gastrinomas, since they progress slowly to liver metastasis. In summary, sporadic and MEN1-associated gastrinomas in the duodenum and pancreas show different clinico-pathological and genetic features. The incidence of sporadic duodenal gastrin-producing tumors is increasing, possibly due to optimized diagnostic procedures. In contrast, pancreatic MEN1-associated gastrinomas seem to be extremely rare. A considerable subset of tumors with immunohistochemical expression of gastrin but without evidence of ZES should be designated as functionally inactive NETs expressing gastrin, but not as gastrinomas.

Topics: Duodenal Neoplasms; Gastrinoma; Gastrins; Germany; Humans; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Prognosis; Switzerland; Zollinger-Ellison Syndrome

In two-thirds of patients with Zollinger-Ellison syndrome (ZES), fasting serum gastrin (FSG) levels overlap with values seen in other conditions. In these patients, gastrin provocative tests are needed to establish the diagnosis of ZES. Whereas numerous gastrin provocative tests have been proposed, only the secretin, calcium, and meal tests are widely used today. Many studies have analyzed gastrin provocative test results in ZES, but they are limited by small patient numbers and methodologic differences. To address this issue, we report the results of a prospective National Institutes of Health (NIH) study of gastrin provocative tests in 293 patients with ZES and compare these data with those from 537 ZES and 462 non-ZES patients from the literature. In 97%-99% of gastrinoma patients, an increase in serum gastrin post secretin (Delta secretin) or post calcium (Delta calcium) occurred. In NIH ZES patients with <10-fold increase in FSG, the sensitivity/specificity of the widely used criteria were as follows: Delta secretin > or =200 pg/mL (83%/100%), Delta secretin >50% (86%/93%), Delta calcium > or =395 pg/mL (54%/100%), and Delta calcium >50% (78%/83%). A systematic analysis of the sensitivity and specificity of other possible criteria for a positive secretin or calcium test allowed us to identify a new criterion for secretin testing (Delta > or =120 pg/mL) with the highest sensitivity/specificity (94%/100%) and to confirm the commonly used criterion for calcium tests (Delta > or =395 pg/mL) (62%/100%). This analysis further showed that the secretin test was more sensitive than the calcium test (94% vs. 62%). Our results suggest that secretin stimulation should be used as the first-line provocative test because of its greater sensitivity and simplicity and lack of side effects. In ZES patients with a negative secretin test, 38%-50% have a positive calcium test. Therefore the calcium test should be considered in patients with a strong clinical suspicion of ZES but a negative secretin test. Furthermore, we found that some clinical (diarrhea, duration of medical treatment), laboratory (basal acid output), and tumoral (size, extent) characteristics correlate with the serum gastrin increase post secretin and post calcium. However, using the proposed criteria, the result of these provocative tests (that is, positive or negative) is minimally influenced by these factors, so secretin and calcium provocative tests are reliable in patients with different clinical,

Topics: Calcium; Eating; Female; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Multivariate Analysis; Prospective Studies; Secretin; Sensitivity and Specificity; Zollinger-Ellison Syndrome

The assessment of fasting serum gastrin (FSG) is essential for the diagnosis and management of patients with the Zollinger-Ellison syndrome (ZES). Although many studies have analyzed FSG levels in patients with gastrinoma, limited information has resulted from these studies because of their small size, different methodologies, and lack of correlations of FSG levels with clinical, laboratory, or tumor features in ZES patients. To address this issue, we report the results of a prospective National Institutes of Health (NIH) study of 309 patients with ZES and compare our results with those of 2229 ZES patients in 513 small series and case reports in the literature. In the NIH and literature ZES patients, normal FSG values were uncommon (0.3%-3%), as were very high FSG levels >100-fold normal (4.9%-9%). Two-thirds of gastrinoma patients had FSG values <10-fold normal that overlap with gastrin levels seen in more common conditions, like Helicobacter pylori infection or antral G-cell hyperplasia/hyperfunction. In these patients, FSG levels are not diagnostic of ZES, and gastrin provocative tests are needed to establish the diagnosis. Most clinical variables (multiple endocrine neoplasia type 1 status, presence or absence of the most common symptoms, prior medical treatment) are not correlated with FSG levels, while a good correlation of FSG values was found with other clinical features (prior gastric surgery, diarrhea, duration from onset to diagnosis). Increasing basal acid output, but not maximal acid output correlated closely with increasing FSG. Numerous tumoral features correlated with the magnitude of FSG in our study, including tumor location (pancreatic > duodenal), primary size (larger > smaller) and extent (liver metastases > local disease). In conclusion, this detailed analysis of FSG in a large number of patients with ZES allowed us to identify important clinical guidelines that should contribute to improved diagnosis and management of patients with ZES.

Topics: Adult; Diagnosis, Differential; Fasting; Female; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Multivariate Analysis; Pancreatic Neoplasms; Prospective Studies; Zollinger-Ellison Syndrome

Many gastric acid hypersecretory states (basal acid output of greater than 15.0 mEq/h) exist for which the etiology is known, such as Zollinger-Ellison syndrome, systemic mastocytosis, antral exclusion, antral predominant Helicobacter pylori gastritis (antral G cell hyperplasia), chronic gastric outlet obstruction, short gut syndrome and basophilic leukemias. However, many hypersecretory patients have no identified etiology for their acid hypersecretion and are designated as idiopathic gastric acid hypersecretors with a basal acid output of greater than 10 mEq/h and a normal serum gastrin level. Because of the gastric acid hypersecretion these patients also commonly have an increased frequency of stools. Idiopathic gastric acid hypersecretion represents a known cause of gastric acid hypersecretion that is far more common than Zollinger-Ellison syndrome and it has a markedly different treatment regimen and natural history. We report a case of a patient with idiopathic gastric acid hypersecretion previously misdiagnosed as having Crohn's disease because of a presenting complaint of diarrhea and mimicking Zollinger-Ellison syndrome because her fasting serum gastrin level was elevated when incorrectly measured in the presence of antisecretory treatment.

Topics: Adult; Anti-Ulcer Agents; Crohn Disease; Diagnosis, Differential; Diarrhea; Female; Gastric Acid; Gastrins; Humans; Omeprazole; Zollinger-Ellison Syndrome

Topics: Biomarkers; Diagnostic Techniques, Endocrine; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Hyperparathyroidism; Radioimmunoassay; Reagent Kits, Diagnostic; Reference Values; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumor of the pancreas (gastrinoma). ZES is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of ZES is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when the hypergastrinemia is associated with a pH <2. Treatment is based on the control of gastric acid hypersecretion and of the malignant tumor and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered at high dosages without drug-related adverse effects. All sporadic, localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like cells, and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy and/or interferon are indicated only in patients with malignant progressive disease. Embolisation and chemoembolisation are effective in controlling clinical symptoms; however, they do not seem to improve survival.

Topics: Biomarkers; Gastrinoma; Gastrins; Humans; Zollinger-Ellison Syndrome

Japanese clinicians and scientists have contributed significantly to reporting, investigating, and managing patients with pancreatic endocrine tumors and other multiple endocrine neoplasias for the past several decades. This article summarizes the latest progress in this field in Japan. Particularly, our contribution to the development of diagnostic and localization methods is reviewed. Further, the present use of somatostatin receptor scintigraphy and the application of the laparoscopic surgery for pancreatic endocrine tumor in Japan are discussed.

Topics: Calcium; Gastrinoma; Gastrins; Injections, Intra-Arterial; Injections, Intravenous; Insulinoma; Japan; Laparoscopy; Pancreas; Pancreatic Neoplasms; Receptors, Somatostatin; Secretin; Zollinger-Ellison Syndrome

Despite general awareness of Zollinger-Ellison syndrome (ZES) by most physicians and more than 3000 articles written about it since 1955, the diagnosis of ZES is still delayed for a mean of 5 years. Recent studies show it is being delayed even more with the widespread use of proton pump inhibitors. A number of tumor markers, in addition to assessing serum gastrin, such as chromogranin A, neuron-specific enolase, and subunits of chorionic gonadotropin, have been proposed for use in either the diagnosis of pancreatic endocrine tumors, such as gastrinomas, or for assessment of tumor extent and growth. In this article important recent insights into the diagnosis of ZES as well as the clinical usefulness of assessing tumor markers for diagnosis and determination of disease extent and growth are discussed. Approximately 25% of ZES cases are due to multiple endocrine neoplasia type 1 (MEN1). A number of important studies in this group of patients are also reviewed. Finally, almost every patient with ZES has marked gastric acid hypersecretion, and its current treatment as well as the long-term possible side effects are reviewed briefly.

Topics: Algorithms; Biomarkers, Tumor; Carcinoid Tumor; Chorionic Gonadotropin; Chromogranin A; Chromogranins; Gastric Acid; Gastrinoma; Gastrins; Gastrointestinal Agents; Humans; Hyperparathyroidism; Multiple Endocrine Neoplasia Type 1; Octreotide; Pancreatic Neoplasms; Phosphopyruvate Hydratase; Proton Pump Inhibitors; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Gastrinoma; Gastrins; Humans; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Prognosis; Zollinger-Ellison Syndrome

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro-oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment.. Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Cytochrome P-450 Enzyme System; Drug Administration Schedule; Drug Costs; Drug Interactions; Duodenal Ulcer; Gastrins; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Rabeprazole; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Stomach Ulcer; Zollinger-Ellison Syndrome

Gastrinoma treatment has evolved considerably in the last 20 years. In particular, the advent of effective acid-reducing pharmacologic agents has changed the primary morbidity of this disease entity from one of acid hypersecretion to one of tumor growth and spread. Thus, while symptoms can be temporized using histamine receptor antagonists, proton pump inhibitors, or somatostatin analogs, cure can be effected only by surgical means. Recent advances in operative techniques and pre- and intra-operative imaging studies, including routine duodenotomy, somatostatin-receptor scintigraphy, and intraoperative ultrasound, have allowed for identification and subsequent resection of more than 95% of gastrinoma tumors. Most experts agree that all sporadic cases of localized gastrinoma should be excised. In addition, debulking of metastatic tumor may improve symptoms and survival when cure cannot be ascertained. There is, however, some controversy as to the surgical approach for gastrinoma found in the setting of multiple endocrine neoplasia, type 1. Because of the usual multiplicity and particular indolence of these tumors, two primary strategies have emerged: aggressive approaches have been advocated in an effort to eradicate all present and potential tumor; and less aggressive, or nonoperative, approaches have been suggested because it is unclear whether intervention offers survival or disease-free benefit in this population. We advocate surgical intervention for patients with gastrinoma and multiple endocrine neoplasia, type 1 when tumors exceed 2.5 cm in size. This tumor size has been associated with a higher likelihood of hepatic metastases, which ultimately affects survival. The role of adjuvant therapies for gastrinoma remains limited.

Topics: Anti-Ulcer Agents; Antineoplastic Combined Chemotherapy Protocols; Catheter Ablation; Combined Modality Therapy; Enzyme Inhibitors; Epidemiologic Methods; Gastrectomy; Gastric Acid; Gastrinoma; Gastrins; Histamine H2 Antagonists; Humans; Liver Transplantation; Multiple Endocrine Neoplasia; Neoplasm Metastasis; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Parathyroidectomy; Proton Pump Inhibitors; Somatostatin; Vagotomy; Zollinger-Ellison Syndrome

The role of gastrin in the pathophysiology of two diseases affecting the human stomach, the Zollinger Ellison syndrome (ZES) and the pernicious anemia (PA), is reviewed. Both diseases present chronic hypergastrinemia but from different origins. The ZES is characterized by the occurrence of ectopic endocrine gastrin-secreting tumors and PA by a fundic atrophic gastritis leading to complete atrophy of fundus and resulting in achlorhydria. In PA, the lack of acid induces continuous gastrin cell activation and is responsible for the subsequent gastrin hypersynthesis and secretion. In ZES, hypergastrinemia causes hypertrophy of the oxyntic mucosa, which, in addition, displays hyperplasia of parietal and mucus cells. In both diseases, hypergastrinemia also induces the hyperproliferation of enterochromaffin-like endocrine cells in the fundic mucosa, which can offer all aspects from hyperplasia, then dysplasia, until true carcinoid tumor. The influence of antisecretory treatments and MEN 1 in the ZES as well as that of several other factors and antrectomy in PA on the behavior of the different gastric cells is evoked. Finally, the role that gastrin and its receptor play in the maintenance of the normal development of gastric mucosa and gastric acid secretion is emphasized by results observed in gene knockout models.

Topics: Anemia, Pernicious; Animals; Atrophy; Autoimmune Diseases; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Hypertrophy; Mice; Mice, Knockout; Multiple Endocrine Neoplasia Type 1; Zollinger-Ellison Syndrome

Gastrin producing ovarian tumor is a rare cause of the Zollinger-Ellison syndrome. We report the case of an ovarian carcinoma showing increased plasma gastrin concentration. A 60-yr-old woman presented with epigastric pain and diarrhea. Physical examination showed a large mass in the lower abdomen. Computed tomography revealed a large multilocular ovarian cyst. Upper gastrointestinal endoscopy examination showed multiple ulcerations of the stomach and duodenum. The plasma gastrin level was 1500 pg/ml. No tumors were found in the pancreas and duodenum, and salpingo-oophorectomy was performed. Histologic examination revealed a mucinous tumor of borderline malignant potential. Immunoperoxidase studies for gastrin showed many gastrin-producing cells within the epithelium of the tumor. There have been 11 cases (including our patient) of gastrin-producing ovarian tumor reported in the literature. We review here the relevant literature. Although ovarian gastrinoma is extremely rare, it should be considered as a possible cause of the Zollinger-Ellison syndrome in women.

Topics: Adenocarcinoma, Mucinous; Female; Gastrins; Hormones, Ectopic; Humans; Middle Aged; Ovarian Neoplasms; Zollinger-Ellison Syndrome

Fundic gland polyps (FGPs) are tiny multiple sessile polyps of the acid-secreting gastric mucosa. They have been described both in a sporadic form, mainly in middle-aged females, and in a syndromic form, associated with familial adenomatous polyposis (FAP)-Gardner's syndrome and attenuated variants (AFAP). They share the same histology, characterised by superficial and deep cystic dilatations, shortened gastric pits, with an inconspicuous lamina propria. They have been for a long time described as innocuous lesions, but some recent reports have shown that FGPs may harbour dysplastic foci and ultimately (particularly syndromic polyps) gastric cancer. Factors influencing their genesis are unknown. A circulating factor in FAP patients has been postulated and a role of female hormones has been suggested for sporadic FGPs. Whereas patients with sporadic FGPs have normal basal acid output, normal fast serum levels of gastrin and pepsinogen I, the role of gastrin seems crucial for the development of cystic changes in flat body-fundus mucosa, and for the appearance of FGPs in patients with Zollinger-Ellison syndrome. A role of H. pylori induced gastritis has been excluded. Actually, patients with both sporadic and syndromic FGPs appear consistently free from H. pylori colonisation, again for an unknown factor(s). Some recent reports have claimed a role for omeprazole in the genesis of FGPs, a highly controversial issue. Ultimately, the nature of FGPs is still debated: some have interpreted them as hamartomatous lesions, others as a peculiar form of hyperplastic polyp.

Topics: Adenomatous Polyposis Coli; Anti-Ulcer Agents; Female; Gardner Syndrome; Gastric Fundus; Gastric Mucosa; Gastrins; Helicobacter pylori; Humans; Male; Omeprazole; Pepsinogen A; Polyps; Stomach Neoplasms; Syndrome; Zollinger-Ellison Syndrome

Topics: Adenoma; Carcinoid Tumor; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Neoplasms, Multiple Primary; Parathyroid Glands; Parathyroid Neoplasms; Stomach; Stomach Neoplasms; Zollinger-Ellison Syndrome

With insulinoma, Zollinger-Ellison syndrome is one of the most common functional islet-cell tumour. Since it is a life-threatening condition, needing appropriate management, the diagnosis must be accurately established. This paper reviews the clinical situations leading to suspect the diagnosis and the biological tests, mainly the secretin test, that confirm the diagnosis. The different ways of performing the secretin test and the respective results are presented. This review will also focus on some aspects of the diagnosis of multiple endocrine neoplasia type 1 in these patients.

Topics: Age of Onset; Diagnosis, Differential; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Prognosis; Zollinger-Ellison Syndrome

Gastrinomas secrete gastrin and cause symptoms related to gastric acid hypersecretion that can be controlled by antisecretory medications. Primary tumors are located within the pancreas or duodenum and 60% metastasize. Liver metastases are associated with decreased survival. Localization studies especially somatostatin receptor scintigraphy are indicated to image the extent of disease. Surgery is indicated to potentially cure the patient, or control the malignant tumoral process and prolong survival.

Topics: Diagnostic Imaging; Duodenal Neoplasms; Gastric Acid; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Survival Rate; Zollinger-Ellison Syndrome

The rationale for a multifaceted operative procedure in all MEN 1 patients with pancreaticoduodenal neuroendocrine disease who present without liver metastases is presented. The results in 36 patients with MEN 1 ZES are encouraging in that more than two-thirds are eugastrinemic and none have liver metastases after follow-up as long as 20 years.

Topics: Adult; Duodenal Neoplasms; Female; Follow-Up Studies; Gastrins; Hormones; Humans; Liver Neoplasms; Male; Mass Screening; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Octreotide; Pancreatectomy; Pancreatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Zollinger-Ellison Syndrome

Topics: Betazole; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Gastritis; Humans; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Gastrinoma; Gastrins; Humans; Magnetic Resonance Imaging; Pancreatic Neoplasms; Radionuclide Imaging; Tomography, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

The enterochromaffin-like (ECL) cell of the oxyntic, acid-secreting mucosa is at present the most extensively studied endocrine cell type in the gastrointestinal tract. It is functionally related to acid secretion through paracrine release of histamine. Its ability to undergo proliferation in response to the trophic stimulus of hypergastrinemia has important implications in pathology, being involved in the development of ECL-cell carcinoid tumors of rodents treated with powerful inhibitors of acid secretion as well as in that of most human gastric carcinoids which, with rare exceptions, are composed of ECL cells. The various aspects of the ECL-cell response to hypergastrinemia in humans are discussed in this review. The trophic effect of gastrin is specific for ECL cells and its sensitivity is enhanced by the female sex and by the genetic background of the multiple endocrine neoplasia type 1 (MEN-1) syndrome. Exposure of ECL cells to hypergastrinemia induces peculiar changes in the structure of cytoplasmic granules and triggers the phenotypic expression of a novel protein, the alpha subunit of glycoprotein hormones, absent in normal cells. The ECL-cell hyperplasia driven by hypergastrinemia may influence the hypersecretory gastric state of patients with Zollinger-Ellison syndrome (ZES) by inappropriate intramucosal secretion of histamine and may contribute to the high circulating levels of basic fibroblast growth factor (bFGF), an ECL-cell product responsible for parathyroid mitogenic effects in MEN-1 patients. However, hypergastrinemia per se cannot promote evolution of hyperplasia into carcinoid tumors, for which additional unknown factors, particularly associated with atrophic gastritis or MEN-1 syndrome, are required. ECL-cell carcinoids developing within these backgrounds have a strikingly more favorable course than their gastrin-independent counterpart. Suppression of hypergastrinemia, either by antrectomy or treatment with somatostatin analogues, may induce regression of both ECL-cell hyperplasia and gastrin-sensitive ECL-cell carcinoids.

Topics: Carcinoid Tumor; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Hyperplasia; Stomach Neoplasms; Zollinger-Ellison Syndrome

In the Zollinger-Ellison syndrome, fundic argyrophil carcinoid tumors occur almost exclusively in the small subgroup of patients who also have multiple endocrine neoplasia type 1. In these patients, tumor development seems related to the same genetic alterations as those observed in other endocrine tumors related to multiple endocrine neoplasia type 1. We report here the second detailed case of a patient with sporadic Zollinger-Ellison syndrome who developed an argyrophil carcinoid tumor in nonatrophic fundic mucosa, suggesting that chronic hypergastrinemia may lead to fundic carcinoid development in nongenetically predisposed patients.

Topics: Aged; Biopsy; Carcinoid Tumor; Chronic Disease; Diagnosis, Differential; Female; Gastric Fundus; Gastric Mucosa; Gastrins; Humans; Multiple Endocrine Neoplasia Type 1; Silver Staining; Stomach Neoplasms; Zollinger-Ellison Syndrome

Gastric carcinoid tumors were previously believed to be rare lesions, representing less than 2% of all carcinoid tumors and less than 1% of all stomach neoplasms. More recent studies have demonstrated that they may constitute as much as 10-30% of carcinoid tumors. Patients with conditions associated with hypergastrinemia, such as chronic atrophic gastritis, Zollinger-Ellison syndrome with multiple endocrine neoplasia type 1 (ZES-MEN-1), and pernicious anemia, display a markedly elevated incidence of gastric carcinoid tumor formation. A classification system distinguishing three types of gastric carcinoid tumor has been proposed: 1) tumors associated with chronic atrophic gastritis, 2) tumors associated with Zollinger-Ellison syndrome, and 3) sporadic lesions. Tumors that develop in association with hypergastrinemia are usually composed of enterochromaffin-like (ECL) cells, in contrast to sporadic lesions that contain a variety of endocrine cell types (enterochromaffin, ECL, X). In both intact animal models such as the rat and Praomys (mastomys) natalensis and in isolated purified ECL cell preparations, gastrin has been demonstrated to exert a powerful trophic effect on ECL cells, in addition to stimulating histamine secretion. It is apparent that hypergastrinemia-associated gastric carcinoids display relatively benign biological behavior. Sporadic lesions require aggressive surgical management on diagnosis. Type I and type II (hypergastrinemia-associated) lesions can be managed initially by endoscopic excision of accessible tumors, followed by endoscopic surveillance. If tumors recur, antrectomy and local excision may be used to remove the source gastrin, resulting in cure in the vast majority of patients.

Topics: Animals; Carcinoid Tumor; Decision Trees; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Incidence; Multiple Endocrine Neoplasia Type 1; Stomach Neoplasms; Zollinger-Ellison Syndrome

Patients with peptic ulcer disease who do not have Helicobacter pylori infection or a history of NSAID use may have the syndrome. Acid secretion can be controlled medically, and tumor resection may be curative in selected patients.

Topics: Diagnosis, Differential; Female; Gastrins; Humans; Middle Aged; Multiple Endocrine Neoplasia; Prognosis; Zollinger-Ellison Syndrome

ECL cells are argyrophilic endocrine cells of the stomach. Their distribution is species specific, however they are consistently located in the oxyntic mucosa and, in particular, in very close contact with the adenomeres of acidopeptic glands. ECL cells store histamine and are considered a key element in the mechanisms of gastric acid secretion as controlled by gastrin stimulus. Their peculiar anatomical disposition and secretory properties strongly suggest that ECL cells exert their function by a paracrine mechanism, i.e. by releasing histamine in the extracellular spaces surrounding acid-producing parietal cells. ECL cell activity is strongly stimulated by gastrin, which, once applied as a long-standing stimulus, also exerts a potent proliferating effect. Long-lasting hypergastrinaemia has been demonstrated to elicit ECL cell proliferation in laboratory animals, inducing ECL cell hyperplasia, dysplasia and ECL cell tumours, i.e. argyrophilic gastric carcinoids. However, in experimental rodents it is believed that hypergastrinaemia is not per se a stimulus capable of inducing ECL cell transformation, a predisposing genetic background being required for tumour development in endocrine organs. In man, long-standing hypergastrinaemia exerts the same proliferative pressure on ECL cells and is associated with hyperplasia with or without dysplastic changes and carcinoid development. Clinical evidence suggests that other factors, both genetic and environmental, are required to induce ECL cell transformation and carcinoid development. For this reason human gastric argyrophilic ECL carcinoids are subdivided into three main groups depending on their clinical background: (1) gastric carcinoids in patients with chronic atrophic gastritis; (2) gastric carcinoids in patients with Zollinger-Ellison and multiple endocrine neoplasia type 1 syndrome (MEN-ZES); and (3) solitary, sporadic gastric carcinoids. The clinical assessment of carcinoid-bearing patients is strongly recommended for better diagnosis and management of patients.

Topics: Animals; Carcinoid Tumor; Enterochromaffin Cells; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Histamine Release; Humans; Multiple Endocrine Neoplasia; Omeprazole; Parietal Cells, Gastric; Stomach Neoplasms; Zollinger-Ellison Syndrome

Awareness of the sometimes subtle features of Zollinger-Ellison syndrome is important in order not to miss the diagnosis. Immediately after initial diagnostic tests, the patient should be given antisecretory medication, while tests for the type of Zollinger-Ellison syndrome and tumour extent can be delayed. Acid output should be decreased to < 10 mmol/h to control symptoms and prevent complications. Histamine H2-antagonists remain the best available intravenous therapy but omeprazole is the most effective long-term oral therapy and has proved to be safe in nearly 10 years of continuous use. The management of the gastrinoma has changed in recent years since the discovery that the majority of gastrinomas arise outside the pancreas. Exploratory surgery with tumour resection is the treatment of choice in sporadic Zollinger-Ellison syndrome but there are few indications for surgery in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type-1. None of the available therapies for metastatic gastrinoma is very effective.

Topics: Diagnosis, Differential; Gastric Acid; Gastrinoma; Gastrins; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Multiple Endocrine Neoplasia; Omeprazole; Secretin; Zollinger-Ellison Syndrome

Gastrointestinal hormones are chemical messengers that regulate a broad range of physiologic functions. Although primarily expressed within tissues of the gut, these peptide hormones are widely distributed throughout the body and act on multiple target tissues. Furthermore, these regulatory peptides can exist in multiple molecular forms that may bind to multiple cell-surface receptors coupled to one of several possible signal transduction systems leading to diverse biologic responses. With such an expansive field to study, it is not surprising that gut endocrinologists have embraced the new techniques that are emerging from the revolution of molecular biology. Beginning with the first construction of a recombinant DNA molecule by Paul Berg in 1971, molecular biology has developed many new techniques that have been rapidly adopted by gut endocrinologists to enable a more detailed understanding of gastrointestinal function. The merging of these two fields has led to a new area of research, molecular gut endocrinology, or the study of gut physiology and endocrinology at the level of individual molecules (ranging from polypeptide-surface receptors to small-molecule second messengers to DNA sequences). Gut cells are constantly bombarded by numerous hormones, and the tightly regulated physiologic status of each cell is becoming more clearly understood.

Topics: Animals; Cholecystokinin; Digestive System Physiological Phenomena; Dogs; Endocrinology; Gastrins; Humans; Molecular Biology; Radioimmunoassay; Rats; Receptors, Cholecystokinin; Signal Transduction; Tumor Cells, Cultured; Zollinger-Ellison Syndrome

Topics: Biomarkers, Tumor; Duodenal Neoplasms; Gastrins; Humans; Multiple Endocrine Neoplasia; Zollinger-Ellison Syndrome

Topics: Carcinoid Tumor; Enterochromaffin Cells; Female; Gastrins; Humans; Male; Omeprazole; Pyloric Antrum; Sex Factors; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenocarcinoma; Carcinoid Tumor; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Omeprazole; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Duodenal Ulcer; Gastrinoma; Gastrins; Humans; Kidney Failure, Chronic; Pancreatic Neoplasms; Pyloric Antrum; Zollinger-Ellison Syndrome

Of 44 patients with the Zollinger-Ellison syndrome treated at our institution, nine appeared to have undergone "regression" of their gastrinomas. Six of the nine patients had sporadic gastrinomas and became permanently eugastrinemic following excision of nodal metastases and total gastrectomy (n = 4), antrectomy (n = 1), or pancreatoduodenectomy (n = 1) (mean survival, 13 years). The other three patients had Zollinger-Ellison syndrome as part of the multiple endocrine adenopathy type 1 syndrome and became temporarily eugastrinemic after total gastrectomy (mean survival, 11 years). Occult submucosal duodenal-wall microgastrinomas (mean size, 3.0 mm) were found to have been serendipitously excised in four patients. Long-term follow-up of these nine patients, as well as of six other patients described in the literature, demonstrates that excision of occult duodenal-wall gastrinomas provides a plausible explanation for the phenomenon of apparent regression of primary gastrinomas and the eugastrinemia that may follow total gastrectomy.

Topics: Adolescent; Adult; Aged; Duodenal Neoplasms; Female; Follow-Up Studies; Gastrectomy; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Neoplasm Regression, Spontaneous; Neoplasms, Multiple Primary; Neoplasms, Unknown Primary; Pancreatic Neoplasms; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Pancreas; Protein Precursors; Protein Processing, Post-Translational; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Child; Cimetidine; Diagnosis, Differential; Famotidine; Gastrectomy; Gastrins; Humans; Middle Aged; Prognosis; Ranitidine; Zollinger-Ellison Syndrome

A 36-yr-old man was admitted to our hospital complaining of severe vomiting and diarrhea. Upper gastrointestinal series showed deformity of the duodenum. Serum gastrin level was very high (1,829 pg/ml) and secretin provocative test presented a positive result (peak 4,535 pg/ml). We diagnosed his illness as Zollinger-Ellison syndrome, but failed to identify the site of tumor. His symptoms were controlled with cimetidine 1,600 mg qid, but serum gastrin level was increasing. A year after the first admission, computed tomographic scan and selective angiography demonstrated the tumor, and surgery was performed. A solitary 2-cm tumor was noted at the surface of mesenterium of the duodenum. Frozen and paraffin section of the tumor revealed islet cell tumor apparently within a lymph node. Immunohistological examination revealed positive staining for gastrin alone. No other tumors were detectable by inspection and palpation during the operation. After excision of the tumor, serum gastrin and secretion test were normalized, and the patient remains asymptomatic 1 yr after surgery.

Topics: Adult; Cimetidine; Gastrins; Humans; Lymph Nodes; Male; Mesentery; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Neoplasms; Duodenum; Female; Gastrectomy; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Multiple Endocrine Neoplasia; Zollinger-Ellison Syndrome

Recent advances in understanding the physiology and pathophysiology of the gastrointestinal hormone, gastrin, are reviewed. Details of gastrin biosynthesis, secretion, and cellular actions may have broad implications for other peptide hormones. Potentially useful antigastrin drugs are described. Areas of future development are suggested.

Topics: DNA Replication; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Peptic Ulcer; Receptors, Gastrointestinal Hormone; Stomach Neoplasms; Vagotomy; Zollinger-Ellison Syndrome

Topics: Combined Modality Therapy; Diagnosis, Differential; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Multiple Endocrine Neoplasia; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome is being detected at an earlier stage through liberal use of serum gastrin testing and application of secretin provocative tests if needed. The peptic ulcer disease of patients with Zollinger-Ellison syndrome can usually be controlled by large doses of one of the new potent gastric acid inhibitors. A battery of preoperative localizing tests can then be applied to guide exploratory laparotomy in non-MEN I patients. The tumor should be resected if possible, and continued low gastrin levels after operation provide evidence of a complete resection. It is reasonable to perform a parietal cell vagotomy at celiotomy because it will facilitate control of acid secretion if tumor resection is not successful. The only need for total gastrectomy is in a few patients whose acid secretion cannot be controlled with H2 receptor antagonists or who cannot comply with medical therapy. When no tumor is found at celiotomy, the prognosis for long-term tumor-free survival is excellent. Unfortunately, if unresectable hepatic metastases are present at operation, the patient is likely to die from metastatic tumor.

Topics: Calcium; Diagnosis, Differential; Gastrectomy; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Multiple Endocrine Neoplasia; Secretin; Zollinger-Ellison Syndrome

Gastrin is the most important peptide in the regulation of gastric acid secretion. This communication reviews important new developments in our knowledge of its synthesis, action, and pathophysiology. The gene for human gastrin has been isolated, and it encodes a pre-pro-gastrin which is a 101-aminoacid peptide containing within it the structure of big gastrin (G34) with a C-terminal glycine extension. Post-translational processing by alpha-amidation of the glycine-extended progastrin results in generation of the active forms of the peptide (G34, G17). When gastrin binds to its receptor on the parietal cell, phosphatidylinositol biphosphate (IP2) in the plasma membrane is converted to inositol 1,4,5-triphosphate (IP3), which acts as the secondary intracellular messenger to increase intracellular calcium and initiate the process that eventually leads to acid secretion. Although an abnormality in gastrin release or action is not thought to be crucially important in the genesis of duodenal ulcer, these patients nevertheless demonstrate increased postprandial gastrin release, and a greater sensitivity of their parietal cells to gastrin. Hypergastrinemia is the cause of peptic ulceration in the Zollinger-Ellison syndrome, in primary gastrin cell hyperplasia or hyperfunction, and in the retained antrum syndrome. Ulcerogenic hypergastrinemia must be distinguished from hypergastrinemia that is secondary to hypoacidity or anacidity, as is seen in atrophic gastritis or postvagotomy.

Topics: Female; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Parietal Cells, Gastric; Peptic Ulcer; Pyloric Antrum; Zollinger-Ellison Syndrome

Topics: Animals; Digestion; Digestive System Diseases; Digestive System Physiological Phenomena; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Secretions; Peptides; Zollinger-Ellison Syndrome

Topics: Animals; Digestive System; Digestive System Physiological Phenomena; Duodenal Ulcer; Gastric Acid; Gastrins; Gastritis; Histamine; Histamine H2 Antagonists; Humans; Intrinsic Factor; Liver Circulation; Pepsinogens; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Regional Blood Flow; Stomach; Stomach Ulcer; Zollinger-Ellison Syndrome

Recent advances in the medical therapy of duodenal ulcer support the long held concept that acid hypersecretion is an important pathophysiological abnormality in the majority of patients with duodenal ulcer. The origin of acid hypersecretion is heterogeneous (Table 1). Certain specific physiologic abnormalities that lead to acid hypersecretion may have a genetic basis. The various physiologic abnormalities, alone or in combination, may lead to two final common pathways: abnormally large meal-stimulated and nocturnal acid secretion. Indeed, the success of medical therapy aimed at the control of postprandial acid secretion alone or that of nocturnal acid secretion alone strongly support the significance of these two final acid hypersecretory pathways.

Topics: Circadian Rhythm; Duodenal Ulcer; Eating; Enterochromaffin Cells; Ethnicity; Gastric Acid; Gastrins; Gastrointestinal Motility; Humans; Hypertrophy; Parietal Cells, Gastric; Pyloric Antrum; Secretory Rate; Vagus Nerve; Zollinger-Ellison Syndrome

Pirenzepine is a 'selective' antimuscarinic agent which, unlike classic anticholinergic agents, inhibits gastric acid secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular and urinary functions. On a weight basis, pirenzepine has one-tenth to one-eighth the potency of atropine in inhibiting stimulated gastric acid secretion in humans. Extensive controlled trials utilising endoscopy in outpatients with duodenal ulcers indicate that patient response to pirenzepine is dose related. Doses of 100 to 150 mg/day are superior to placebo in promoting duodenal ulcer healing and in diminishing day and night pain and supplementary antacid consumption. At such doses, the efficacy of pirenzepine appears to be superior to that of gefarnate 300 mg/day and generally not significantly different from that of cimetidine 1 g/day in treating duodenal ulcers. A beneficial effect of pirenzepine in the prevention of duodenal ulcer recurrence was apparent in preliminary studies in small numbers of patients, but its efficacy in this regard needs further confirmation and the optimum dosage determined. Less extensive data on the treatment of benign gastric ulcers suggest that pirenzepine 100 to 150 mg/day is superior to placebo and gefarnate 300 mg/day and does not differ significantly from cimetidine 1 g/day promoting gastric ulcer healing. Pirenzepine is well tolerated by most patients, with a low incidence of typical antimuscarinic effects on the gastrointestinal tract, genitourinary system or heart being reported in clinical studies. However, dry mouth and blurred vision are the more common side effects with clinically effective doses. Thus, pirenzepine appears to have relatively selective antimuscarinic activity, although controlled studies comparing pirenzepine and conventional antimuscarinics in patients with peptic ulcer disease have not been reported.

Topics: Benzodiazepinones; Dialysis; Dyspepsia; Gastric Acid; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Absorption; Intestinal Mucosa; Kinetics; Nitrates; Pancreas; Parasympatholytics; Pepsin A; Peptic Ulcer; Pirenzepine; Receptors, Muscarinic; Recurrence; Tissue Distribution; Zollinger-Ellison Syndrome

Initial reports of patients with Zollinger-Ellison syndrome were characterized by a long history of recurrent peptic ulcer and multiple operations. Diagnosis was usually made by a combination of clinical history and roentgenograms of the upper aspect of the gastrointestinal tract. Diagnosis was confirmed by the demonstration of elevated basal plasma gastrin levels. The management of the disease included either tumor excision or gastric resection, but more often it included a total gastrectomy. The mortality was high, often because of late recognition of the disease or operative problems related to inadequate control of the hypersecretion of acid. This review is a brief synopsis of the evolution and status of the different diagnostic and therapeutic techniques involved in the contemporary management of patients with gastrinomas. The diagnostic emphasis has shifted away from gastrointestinal contrast studies. Techniques have been developed both for the biochemical diagnosis of the condition and for the topographic localization of the site of the lesion. The use of acid secretory data has declined in value with the development of more elegant techniques for the detection of elevated levels of plasma gastrin in the systemic circulation and the use of portal venous sampling for identifying the source. Thus, the results of sophisticated procedures such as percutaneous transhepatic portopancreatic venous sampling or selective angiography provide additional information. The biochemical diagnosis of gastrinoma is best supported by the evaluation of provocative testing with either calcium or secretin rather than measurement of the basal levels of plasma gastrin. The introduction of potent H2 receptor antagonists has produced support for more conservative management of the disease. The incidence of significant complications during such therapy limits its over-all efficacy. The use of these drugs has, however, facilitated both the conservative and the operative management of patients with extensive sequelae of acid hypersecretion due to a gastrin-secreting tumor. It is probably reasonable to surgically stage the disease of all patients with hypergastrinemia of neoplastic origin since a small percentage (10 per cent) may have a solitary benign lesion which is curable by resection. Total gastrectomy under elective circumstances still has considerable merit. Preliminary data have indicated that alternative, lesser surgical procedures, such as proximal gastric vagotomy,

Topics: Adult; Antineoplastic Agents; Bombesin; Calcium; Gastrectomy; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Secretin; Zollinger-Ellison Syndrome

Topics: Bombesin; Calcium; Eating; Gastric Emptying; Gastrins; Gastrointestinal Hormones; Histamine H2 Antagonists; Humans; Kidney Failure, Chronic; Peptic Ulcer; Pyloric Stenosis; Secretin; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Cimetidine; Esophagitis; Female; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Parathyroid Glands; Prognosis; Secretin; Zollinger-Ellison Syndrome

Topics: Burimamide; Chemical Phenomena; Chemistry; Cimetidine; Duodenal Ulcer; Esophagitis, Peptic; Gastric Acid; Gastrins; Gastrointestinal Hemorrhage; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Hypersensitivity; Intrinsic Factor; Kinetics; Malabsorption Syndromes; Metiamide; Pancreas; Pepsin A; Ranitidine; Receptors, Histamine H2; Stomach Ulcer; Stress, Psychological; Zollinger-Ellison Syndrome

Topics: 3,4-Dihydroxyphenylacetic Acid; Amylases; Animals; Brain Chemistry; Cysteamine; Dopamine; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Hormones; Humans; Mice; Nitriles; Norepinephrine; Rats; Secretin; Terminology as Topic; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

The Zollinger-Ellison syndrome (ZES) is caused by mainly pancreatic, gastrin-producing tumours, which show a high rate of malignancy. The clinical picture is dominated by gastric hypersecretion, which results in the development of peptic ulcerations of the stomach and duodenum, reflux esophagitis, or diarrhea. The differentiation from other types of hypergastrinemia is done by provocative tests, mainly the secretin-test. Because of the high malignancy rate, therapeutically, a symptomatic treatment of gastric hypersecretion by H2-receptor antagonists or in cases of ineffective conservative treatment total gastrectomy is performed. In patients with duodenal gastrinomas or in the rare cases with benign pancreatic tumours resection of the tumours is the therapy of choice.

Topics: Benzimidazoles; Calcium; Cimetidine; Diarrhea; Duodenal Ulcer; Female; Fluorouracil; Gastrectomy; Gastric Acid; Gastrins; Glucagon; Humans; Male; Middle Aged; Omeprazole; Pancreatic Neoplasms; Prognosis; Ranitidine; Secretin; Streptozocin; Zollinger-Ellison Syndrome

The application of radioimmunoassay of insulin, C-peptide, gastrin, glucagon, vasoactive intestinal polypeptides (VIP), somatostatin, human pancreatic polypeptides (hPP), substance P and neurotensin to detect endocrine tumors of the pancreas and other organ systems is undoubtedly important in the clinical management of patients suspected of having tumors that secrete these hormones. Radioimmunoassays of the above gut peptides have certain degrees of specificity and sensitivity; however, there are several factors that need to be considered in the interpretation of results since heterogeneity of molecular forms does occur and the varied radioimmunoassay techniques use different antibodies that may yield different results. It is, therefore, important that each laboratory establish its own normal values, determine the molecular species that each assay is detecting, and also determine the false positivity of the methodology. The same endocrine tumor may contain and secrete several detectable peptides, but the syndrome may relate to only one peptide. Although the simultaneous measurement of multiple peptides in patients with benign gastrointestinal disease has yielded information that contributes to our understanding of the complexities of gut neuroendocrine interaction, the pathophysiological role of gut peptides and their clinical relevance need further evaluation.

Topics: Animals; Diagnosis, Differential; Digestion; Food; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Kidney Diseases; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Vagus Nerve; Vasoactive Intestinal Peptide; Vipoma; Zollinger-Ellison Syndrome

Sulfated gastrins resemble cholecystokinins (CCK) both structurally and functionally. They are less potent than CCK in stimulating gallbladder contraction and pancreatic enzyme secretion, but the plasma concentrations of sulfated gastrin are higher than those of CCK. Therefore, sulfated gastrins may contribute significantly to the endogenous CCK activity. The degree of sulfation of gastrin differs with the localization in the digestive tract. In the antrum and duodenum of normal subjects 45% of the gastrins are sulfated, as in serum. In contrast, the sulfation of gastrin is complete in the jejunum (human) and in the pancreas (rat and cat). Hence, the degree of sulfation of gastrin is similar to that of CCK in the jejunum. The degree of sulfation in antrum, duodenum and serum diminishes with hypergastrinemia, and is thus significantly lower in patients with gastric ulcer or pernicious anemia than in healthy subjects. In the Zollinger-Ellison syndrome, the degree of sulfation of gastrin varies greatly (20-90%) and the distribution between small and large gastrins is equally variable. However, sulfation and proteolytic processing follows a parallel course; complete processing to smaller components is accompanied by complete sulfation of the peptide and vice versa. During ontogenesis sulfated gastrins may be of special importance, since they are the only sulfated members of the gastrin/CCK family of peptides which occur in substantial quantities in the early fetus. Tyrosine-O-sulfation has now been recognized as a widespread modification, and sulfated tyrosyl residues in gastrin, CCK and leu-enkephalin are examples of a derivatization which can govern the biological activity of regulatory peptides.

Topics: Anemia, Pernicious; Animals; Duodenum; Gastrins; Humans; Jejunum; Pancreas; Peptic Ulcer; Pituitary Gland; Pyloric Antrum; Radioimmunoassay; Species Specificity; Sulfates; Tyrosine; Zollinger-Ellison Syndrome

The past 20 years have seen gastrin attain true hormonal status. Its structure has been characterized, it has been synthesized, radioimmunoassays for its measurement in blood and tissues have been developed and its physiology and metabolism elucidated. Of much interest to clinicians has been the association between gastrin and tumours of the pancreas (gastrinomas) and atrophic gastritis. The advent of gastrin measurement has facilitated the diagnosis of gastrinoma and the availability of powerful acid suppressants has altered the therapy of gastrinoma.

Topics: Duodenal Ulcer; Gastrins; Gastritis, Atrophic; Humans; Kidney Failure, Chronic; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Animals; Dogs; Gastric Mucosa; Gastrins; Graft Rejection; Humans; Insulin; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Metabolic Clearance Rate; Proteinuria; Rats; Zollinger-Ellison Syndrome

Topics: Cyclic AMP; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Mucus; Neurotransmitter Agents; Pepsin A; Peptic Ulcer; Prostaglandins; Zollinger-Ellison Syndrome

Four patients with Zollinger-Ellison Syndrome (ZES) are presented to highlight the difficulties in the recognition, diagnosis and management of this rare disease. The presentation of ZES is usually indistinguishable from ordinary peptic ulcer disease and in those patients with symptoms not related to peptic ulcer, i.e., diarrhoea, as their main complaint, the diagnosis is often not even considered. A high index of suspicion is required, however, in patients with recurrent ulcers, multiple ulcers and in those with resistant or rapidly relapsing ulcers after conventional therapy. A presumptive diagnosis can be made by the demonstration of grossly elevated fasting serum gastrin levels combined with a secretin stimulation test in doubtful cases. The main problem is the location of the gastrin-secreting tumour which is usually pancreatic but often too small to be detected by currently available techniques. Histamine H2-receptor antagonists in high doses are effective in controlling the gastric acid hypersecretion which is chiefly responsible for the morbidity and mortality in ZES. They provide the treatment of choice in patients where the tumour cannot be located, though every attempt should be made to do this as surgery is the treatment of choice for this invariably malignant tumour. Total gastrectomy is now reserved for those patients in whom medical therapy has failed. The role of chemotherapy in metastatic disease has yet to be established.

Topics: Adult; Angiography; Diagnosis, Differential; Duodenoscopy; Female; Gastrectomy; Gastric Acid; Gastrins; Gastroscopy; Histamine H2 Antagonists; Humans; Male; Middle Aged; Peptic Ulcer; Tomography, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

Topics: Acute Disease; Amylases; Antacids; Anti-Ulcer Agents; Calcitonin; Depression, Chemical; Enzyme Inhibitors; Gastric Acid; Gastrins; Hormones; Humans; Pancreas; Pancreatitis; Zollinger-Ellison Syndrome

Over the last few years the approach to managing patients with the Zollinger-Ellison syndrome has changed dramatically. The establishment of gastrin hypersecretion by a non-beta islet cell tumor as responsible for the gastric acid hypersecretion, and the subsequent development and widespread availability of gastrin radioimmunoassays have changed the criteria generally used for diagnosis and have led to an increased understanding of syndromes that can mimic Zollinger-Ellison syndrome. With the availability of histamine H2-receptor antagonists, gastric acid hypersecretion can be controlled medically in almost all patients with Zollinger-Ellison syndrome, obviating routine total gastrectomy. With the reduced mortality from gastric acid hypersecretion, increased attention is being focused on the natural history of the gastrinoma. Newer methods of localizing tumors are being investigated with a view to surgical removal of the gastrinoma, and the importance of developing an affective chemotherapeutic regimen is becoming increasingly apparent.

Topics: Adolescent; Adult; Aged; Angiography; Animals; Diagnosis, Differential; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Rats; Tomography, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

Topics: Calcium; Diagnosis, Differential; Duodenal Ulcer; False Negative Reactions; False Positive Reactions; Gastrectomy; Gastrins; Humans; Infusions, Parenteral; Injections, Intravenous; Jejunal Diseases; Peptic Ulcer; Secretin; Stomach Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Chromaffin System; Cytoplasmic Granules; Duodenal Ulcer; Enterochromaffin Cells; Gastrins; Humans; Hyperplasia; Immunologic Techniques; Pepsinogens; Pyloric Antrum; Zollinger-Ellison Syndrome

The procedures of radioimmunoassays for gastrin are presented in this paper. Techniques are described and evaluated with special reference to preparation of radioiodinated gastrin, purification of monoiodinated gastrin, characterisation of the immunochemical properties of radiolabelled gastrin, raising and characterisation of specific antibodies, incubation conditions, separation of bound and free hormone and treatment of data. Factors contributing to discrepancies of radioimmunoassay results and problems encountered are discussed. Methods employed by the authors in gastrin radioimmunoassay are described. Commercially available gastrin kits are also compared.

Topics: Animals; Antibody Formation; Cattle; Chromatography, Gel; Chromatography, Ion Exchange; Duodenal Ulcer; Gastrins; Humans; Iodine Radioisotopes; Rabbits; Radioimmunoassay; Reagent Kits, Diagnostic; Secretin; Swine; Zollinger-Ellison Syndrome

An assessment of treatment methods for the Zollinger-Ellison syndrome over 25 years suggests that the dual surgical approach of excision of resectable tumor and total gastrectomy provides the greatest possibility of attaining tumor and serum gastrin control. Normal serum gastrin levels and reduction of tumor status, not observed with nonoperative management, were attained by surgical treatment, particularly when the tumor (or hyperplasia) was limited to the pancreas, stomach, duodenum and regional lymph nodes. Eleven of 16 such operations resulted in tumor control, and 10 of these patients developed normal serum gastrin concentrations. In elective clinical situations combined medical and surgical therapy is a rational approach allowing confirmation of diagnosis and safe, definitive surgical control of the syndrome before metastases occur.

Topics: Cimetidine; Gastrectomy; Gastrins; Guanidines; Humans; Neoplasm Metastasis; Retrospective Studies; Streptozocin; Zollinger-Ellison Syndrome

Topics: Acromegaly; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Hyperparathyroidism; Ileal Diseases; Pyloric Antrum; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Female; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Antineoplastic Agents; Cimetidine; Diagnosis, Differential; Gastrectomy; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Middle Aged; Postgastrectomy Syndromes; Pyloric Antrum; Secretin; Vagotomy; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Acromegaly; Adenoma; Adenoma, Islet Cell; Adolescent; Adult; Aged; Calcium; Cushing Syndrome; Diarrhea; Female; Gastric Acid; Gastrins; Glucagon; Humans; Hyperinsulinism; Hyperparathyroidism; Hypoglycemia; Hypokalemia; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Polypeptide; Pancreatitis; Parathyroid Glands; Parathyroid Neoplasms; Pituitary Neoplasms; Syndrome; Thyroid Diseases; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Humans; Insulin; Insulin Secretion; Insulinoma; Pancreatectomy; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Age Factors; Aged; Digestion; Fasting; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Middle Aged; Peptic Ulcer; Reference Values; Time Factors; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Female; Gastrins; Humans; Insulin; Insulin Secretion; Male; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Cimetidine; Gastrectomy; Gastric Juice; Gastrins; Humans; Hyperplasia; Neoplasm Metastasis; Postoperative Complications; Pyloric Antrum; Vagotomy; Zollinger-Ellison Syndrome

Topics: Cimetidine; Duodenal Ulcer; Gastric Acid; Gastrins; Guanidines; Humans; Kinetics; Pancreatitis; Time Factors; Zollinger-Ellison Syndrome

Gastrin release does play a part in the cephalic phase of acid secretion in man and is the major mechanism for the gastric phase of acid secretion. The vagal control of gastrin release is most likely mediated by cholinergic and possibly non-cholinergic excitatory fibres, as well as by cholinergic inhibitory fibres. Gastric luminal control of gastrin release is by local food and possibly distension stimulation, as well as by acid inhibition. Of the various causes of hypergastrinaemia, those associated with gastrinoma, G-cell hyperfunction and retained antrum have definite pathogenetic roles. Duodenal ulcer disease is a heterogeneous goup of disorders having different pathogenetic mechanisms. Parietal cell hyperplasia and G-cell dysfunctions, consisting of modest to florid G-cell hyperfunction and hyperplasia with secondary parietal cell hyperplasia, are but some facets of abnormalities that we have been able to identify.

Topics: Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Peptic Ulcer; Pyloric Antrum; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Calcium; Diagnosis, Differential; False Positive Reactions; Food; Gastrectomy; Gastric Acid; Gastric Acidity Determination; Gastrins; Gastroscopy; Glucagon; Humans; Magnesium Sulfate; Peptic Ulcer; Recurrence; Secretin; Zollinger-Ellison Syndrome

The importance of the gastrointestinal hormones to the clinician is considered under three headings: in disease states, diagnostic applications and therapeutic implications. Pearse's APUD (Amine Precursor Uptake and Decarboxylation) theory is referred to, and single and multiple endocrinopathies are discussed with particular referrence to diagnostic criteria and principles of management. The field of gastrointestinal endocrinology is rapidly developing and these peptides will assume an even greater importance to the clinician who must keep abreast with these developments.

Topics: Endoscopy; Esophagitis, Peptic; Gastrins; Gastrointestinal Hormones; Glucagon; Histamine; Humans; Multiple Endocrine Neoplasia; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Bombesin; Cholecystokinin; Cimetidine; Epidermal Growth Factor; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Nerve Tissue; Pancreas; Pancreatic Polypeptide; Pituitary Gland; Secretin; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Studies in animals demonstrate a gastric hormonal phase of pancreatic exocrine secretion. Endogenous or exogenous gastrin causes a marked elevation in the pancreatic enzymes and a lesser increase in the pancreatic volume and bicarbonate. It is possible that these "gastrin" effects may be the basis of a "cephalic" phase of pancreatic secretion. These observations have been only partially confirmed in human subjects with and without the Zollinger-Ellison syndrome. The physiologic importance of these ecbolic actions as well as a possible trophic effect remains to be elucidated.

Topics: Animals; Bicarbonates; Cats; Dogs; Eating; Fistula; Gastrins; Humans; Pancreas; Pentagastrin; Rats; Stomach; Trypsin; Vagotomy; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Animals; Celiac Disease; Child; Duodenal Ulcer; Duodenum; Esophageal Diseases; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Intestinal Mucosa; Intestine, Small; Stomach; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Child; Cimetidine; Eating; Gastrectomy; Gastrins; Humans; Zollinger-Ellison Syndrome

The identification and description of a widely dispersed group of cells of common origin and biochemical characteristics, APUD cells, has allowed a better understanding and classification of endocrine tumors of the pancreas. Similarly, it has enabled the relationships between the endocrine tumors of the multiple endocrine neoplasia type I syndrome and the endocrine tumors of the pancreas to be better appreciated. This has facilitated both diagnosis and management of these conditions. The pluripotentiality of the cells of the APUD system combined with the certain existence of many unidentified peptides suggests the likelihood of other undescribed pancreatic endocrine tumors. Many of these are probably part of the heterogenous group of neoplasms currently designated as carcinoids, since their secretory products and exact cell types are not known. The recognition of the physiologic characteristics and cells of origin of these peptides, amines or other bioactive agents will allow delineation of the symptom complex and the identification of further functional tumors of the pancreas. The development of plasma radioimmunoassays for the various hormones and the appreciation of the specific clinical syndromes related to each tumor have enabled earlier diagnosis. The understanding of the hormonal physiopathologic functions has led to the evolution of specific therapeutic maneuvers. Provocative tests have allowed increased precision of the differential diagnosis, while selective arteriography and pancreatic venous sampling have greatly enhanced the accuracy of topical localization. The role of operation in tumor removal is still prominent, but malignant and recurrent tumors may now also be controlled with specific pharmacotherapy or appropriate endocrine cytotoxic agents. The use of peptides with antagonistic actions or the administration of specific antibodies to the active tumor products are areas of therapy that require further exploration.

Topics: Adult; Apudoma; Carcinoid Tumor; Child; Diagnosis, Differential; Gastrins; Glucagon; Humans; Infant; Insulin; Insulin Secretion; Islets of Langerhans; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Animals; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Nervous System; Pancreas; Pancreatic Neoplasms; Stomach Neoplasms; Zollinger-Ellison Syndrome

After reviewing the more recent acquisitions on the physiology and pathophysiology of gastrin, the authors concentrate on situations of hypergastrinemia, which they divide into a hyperhydrochloric and a hypohydrochloric variety. Among the former, which they subdivide into preoperative and postoperative, the authors discuss problems of differential diagnosis versus peptic ulcers in patients so afflicted. To that end they propose diagnostic policies comprising among other instrumental and laboratory tests the study of gastric secretion, blood gastrin levels in basal conditions and after stimulation by a protein meal, BBS, secretin, and calcium. From analysis of the results of such tests they were able to find a precise nosographic placement for postoperative hypergastrinemia, and from there they arrived at surgical programs aiming to correct postoperative peptic ulcers on the basis of their etiology and pathogenesis.

Topics: Gastrectomy; Gastrins; Humans; Hyperparathyroidism; Peptic Ulcer; Postoperative Complications; Pyloric Stenosis; Stomach Diseases; Vagotomy; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Apudoma; Dehydration; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Parathyroid Neoplasms; Pheochromocytoma; Postgastrectomy Syndromes; Somatostatin; Syndrome; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: APUD Cells; Diagnosis, Differential; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Cholecystokinin; Gastric Juice; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Neoplasms; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides; Precancerous Conditions; Secretin; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adolescent; Adult; Aged; Carcinoid Tumor; Child; Dehydration; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Humans; Hyperplasia; Hypokalemia; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Precancerous Conditions; Serotonin; Somatostatin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Dogs; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Pancreatic Diseases; Radioimmunoassay; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Dogs; Feedback; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Secretin; Swine; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Antacids; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Histamine Antagonists; Humans; Male; Parasympatholytics; Peptic Ulcer; Stomach Ulcer; Zollinger-Ellison Syndrome

Cimetidine is a specific competitive histamine H2-receptor antagonist which effectively inhibits gastric acid secretion and is advocated for the treatment of chronic peptic ulceration, haemorrhage from erosive gastritis, and the control of gastric hypersecretion and peptic ulceration in the Zollinger-Ellison syndrome. Placebo-controlled trials in outpatients have demonstrated its efficacy in promoting the healing of endoscopically diagnosed duodenal ulceration, during a period of 4 to 6 weeks, but its role in the treatment of gastric ulcer is less clear. Preliminary evidence suggests that maintenance therapy with cimetidine reduces the rate of recurrence of duodenal ulcer, but further studies are required to clarify its role in this situation and in the treatment of oesophagitis and acute gastrointestinal haemorrhage. Cimetidine controls the peptic ulceration of Zollinger-Ellison syndrome in most patients when given continuously for up to 2 years. Side-effects have generally been trivial and have very seldom necessitated withdrawal of therapy except in the rare occurrence of gynaecomastia. The haematological abnormalities particularly agranulocytosis, which lead to the withdrawal from clinical use of metiamide, have not been reported with cimetidine, except for 1 case of transient neutropenia. The safety of long-term cimetidine administration has yet to be determined.

Topics: Acute Disease; Animals; Cimetidine; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Hemorrhage; Guanidines; Humans; Intrinsic Factor; Recurrence; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Digestion; Esophageal Achalasia; Esophagitis, Peptic; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Gastritis; Glucagon; Humans; Ileum; Islets of Langerhans; Jejunum; Kidney Failure, Chronic; Liver; Protein Hydrolysates; Pyloric Antrum; Somatostatin; Vagotomy; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Cimetidine, a new histamine H2-receptor antagonist (H.H2.R.A.) is a potent inhibitor of basal and stimulated gastric acid secretion. Contrary to anticholinergics, it does not affect gastric emptying nor does it decrease lower oesophageal sphincter pressure; cimetidine may therefore be used as the treatment of reflux oesophagitis. After prolonged administration of currently used therapeutic doses, basal and post-prandial serum gastrin levels remain unchanged and the parietal cell mass is not increases. Cimetidine toxicity is very low. Cimetidine is effective in promoting healing and pain relief of gastric and duodenal ulcer. In the latter long-term treatment for prevention of relapse is efficient, but the appraisal of its safety remains debated. Efficiency of H.H2.R.A. in the prophylaxis of gastrointestinal haemorrhage in patients with fulminant hepatic failure has been proven. Furthermore, cimetidine has a dramatic ability to control haemorrhage from acute erosive lesions in any seriously-ill patient. It may also be of benefit in the treatment of bleeding from gastric or duodenal ulcer and, whatewer the lesion, in the prevention of bleeding recurrence. In the Zollinger-Ellison syndrome, good results have been obtained but cimetidine treatment must be decided and supervised only by well-informed specialists. Lastly, in patients with severe exocrine pancreatic insufficiency, cimetidine prevents gastric degradation of orally administered pancreatic extracts and decreases steatorrhea.

Topics: Cimetidine; Gastric Juice; Gastrins; Gastrointestinal Hemorrhage; Guanidines; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage; Zollinger-Ellison Syndrome

Somatostatin, under physiological conditions, is a regulator of thyroid stimulating hormone, growth hormone, pancreatic islet-cell hormones and gastrin. In pharmacological dosage, gastric acid output, splanchnic blood flow and plasma renin levels, are influenced. A possible therapeutic effect on increased growth hormone secretion, disturbances of carbohydrate metabolism, gastroenteropathies and renal hypertension, is discussed. The clinical application is limited by the short biological half-life of the substance and the unspecific action on several organs.

Topics: Acromegaly; Animals; Diabetes Mellitus; Diabetic Retinopathy; Gastric Juice; Gastrins; Growth Hormone; Humans; Hypertension; Islets of Langerhans; Pancreatitis; Renin; Somatostatin; Thyrotropin; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adult; Amines; Carboxy-Lyases; Dehydration; Endocrine Glands; Fluorescent Antibody Technique; Gastrins; Glucagon; Humans; Hyperplasia; Intestinal Neoplasms; Intestinal Secretions; Intestines; Male; Multiple Endocrine Neoplasia; Neurosecretory Systems; Pancreas; Paraneoplastic Endocrine Syndromes; Peptides; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Cholecystokinin; Esophageal Achalasia; Esophagogastric Junction; Esophagus; Estradiol; Gastric Juice; Gastrins; Glucagon; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Opossums; Pressure; Progesterone; Secretin; Zollinger-Ellison Syndrome

With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable elect

Topics: Adenoma, Islet Cell; Anemia, Pernicious; Chromaffin System; Digestive System; Duodenal Ulcer; Endocrine System Diseases; Enterochromaffin Cells; Esophagitis, Peptic; Gastrectomy; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Intestinal Mucosa; Metabolic Diseases; Serotonin; Somatostatin; Stomach Neoplasms; Stomach Ulcer; Syndrome; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Calcium; Dietary Proteins; Duodenal Ulcer; Gastric Juice; Gastrins; Gastritis; Glucagon; Humans; Hyperplasia; Intestine, Small; Kidney Failure, Chronic; Pyloric Antrum; Pyloric Stenosis; Secretin; Stomach Neoplasms; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Animals; Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Radioimmunoassay; Stimulation, Chemical; Stomach; Structure-Activity Relationship; Zollinger-Ellison Syndrome

Topics: Adolescent; Age Factors; Calcium; Child; Female; Gastrins; Humans; Male; Methods; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Anemia, Pernicious; Duodenal Ulcer; Gastrectomy; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Liver; Molecular Weight; Peptic Ulcer; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Hyperparathyroidism; Paraneoplastic Endocrine Syndromes; Peptic Ulcer; Pyloric Antrum; Radioimmunoassay; Zollinger-Ellison Syndrome

The author made a review about the origin, the biochemistry the physiological and pathological roles of gastrointestinal peptide hormones. They originate from the APUD cell system, chemically from the ancient growth hormone, or placental lactogen. The theoretical prosecgastrin's first sequencies form the "secretin family", the tail sequencies form the "gastrin family". The author describes many details of their effects on the different gastrointestinal organs, they behave mainly antagonistic way to each other. Finally a discussions is given about their role in the development of peptic ulcer, in the WDHA syndrome and in malabsorption.

Topics: APUD Cells; Cell Differentiation; Dumping Syndrome; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Diagnosis, Differential; Diarrhea; Gastrins; Germany, West; Glucagon; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Malignant Carcinoid Syndrome; Pancreatic Neoplasms; Syndrome; Zollinger-Ellison Syndrome

The treatment with streptozotocin of a patient with metastatic gastrinoma is described. Two courses of intravenous streptozotocin were without effect. However, three months after two doses of 4 g streptozotocin were given into the coeliac axis, there was a marked reduction in hepatic size and a fall in fasting plasma gastrin levels from 1430 pmol/l to 240 pmol/l. Seven months after treatment fasting plasma gastrin levels were 125 pmol/l.

Topics: Adenoma, Islet Cell; Adult; Female; Gastrectomy; Gastrins; Hepatectomy; Humans; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Streptozocin; Zollinger-Ellison Syndrome

The islet cell tumors of the pancreas are now known to produce a variety of polypeptides in addition to insulin. These include glucagon, serotonin, corticotropin, melanocyte-stimulating hormone, gastrin and a secretinlike hormone that may be VIP or a combination of such polypeptides. The development and wide availability of the newer immunoassays for the various recognized hormones as well as candidate hormones of the gut will simplify the diagnosis of these challenging tumors, which up until this time have produced symptoms that were bizarre and often fatal to the patient.

Topics: Achlorhydria; Adenoma, Islet Cell; Angiography; Calcium; Diagnosis, Differential; Diarrhea; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hyperinsulinism; Hyperparathyroidism, Secondary; Neoplasm Metastasis; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Animals; Biogenic Amines; Carcinoid Tumor; Decarboxylation; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Histocytochemistry; Intestinal Mucosa; Islets of Langerhans; Pancreatic Neoplasms; Serotonin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Diarrhea; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Neurosecretory Systems; Pancreatic Hormones; Paraneoplastic Endocrine Syndromes; Prostaglandins; Serotonin; Syndrome; Vasoactive Intestinal Peptide; Werner Syndrome; Zollinger-Ellison Syndrome

Topics: Acromegaly; Adenoma, Islet Cell; Adrenocorticotropic Hormone; Bronchial Neoplasms; Diabetes Mellitus; Gastrins; Glucagon; Growth Hormone; Humans; Hypoglycemia; Neoplasms; Pancreatic Neoplasms; Somatostatin; Thyrotropin; Zollinger-Ellison Syndrome

The forms of gastrin which have been isolated from antral mucosa or Zollinger-Ellison tumour tissue (or both) and characterized chemically are as follows: little gastrin (G17) (LG); big gastrin (G34) (BG); minigastrin (G13); the NH2-terminal 1-13 fragment of G17. All these exist as pairs of peptides which have an identical amino acid sequence and differ solely in that the single tyrosyl residue present may be sulphated. The proportions of the pairs of each peptide show species variation where isolation has been accomplished (e.g. from hog, dog, cat, cow, sheep and man in the case of LG, and hog and man for BG). All these forms of the hormone have been identified immunologically in serum; LG and BG have been identified in duodenal mucosa. Two larger forms of the hormone have been identified immunologically in serum; component I (CI) and 'big big gastrin' (BBG). Material corresponding in size to BBG and CI has been identified in extracts of antral and jejunal mucosa and Zollinger-Ellison tumour. Neither BBG nor CI has been characterized chemically to date and their physiological significance is uncertain. Recent studies suggest that the heterogeneity of gastrins in serum and tissues may be considerably greater than is indicated by the list of components given above.

Topics: Amino Acid Sequence; Amino Acids; Animals; Gastrins; Humans; Molecular Weight; Peptide Fragments; Species Specificity; Zollinger-Ellison Syndrome

Topics: Duodenum; Gastric Mucosa; Gastrins; Humans; Peptic Ulcer; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Gastrectomy; Gastrins; Humans; Hyperparathyroidism; Pepsinogens; Peptic Ulcer; Vagotomy; Zollinger-Ellison Syndrome

In a short survey recent results of research on gastrin are presented. Special stress is laid upon the mechanism of liberating gastrin, the role of the vagus in this process and the consequences of gastric surgery on serumgastrin. In clinical practice the differential diagnosis of hypergastrinemia in ulcer disease is very important, for it will have a decisive influence on the therapeutic decisions and the specific kind of surgical treatment.

Topics: Duodenal Ulcer; Gastrins; Humans; Peptic Ulcer; Postoperative Complications; Vagotomy; Zollinger-Ellison Syndrome

Functioning tumors of the pancreatic islets are now recognized as the source of clinical syndromes affecting the gastrointestinal tract which have a wide variety of catastrophic symptoms. Experiences with thirty-six cases suggest at least four separate diagnostic categories in the ulcerogenic tumor syndrome. These include: a typical history, gastric analysis, and roentgenographic findings with boderline fasting serum gastrin levels; ulcerogenic tumor with evidence of hyperparathyroidism; iatrogenic ulcerogenic syndrome associated with failure of a previous operation for duodenal ulcer; and the classic ulcerogenic syndrome associated with a fulminating ulcer diathesis or diarrhea and high serum gastrin levels. The problems presented at operation include: decisions to be make in the presence of a negative exploration; the finding of a solitary tumor in the wall of the duodenum; solitary pancreatic tumors particularly in the body and tail; ulcerogenic tumors in the very young; liver metastases in the elderly; and the wisdom of removing gross metastases in combination with total gastrectomy. The long-term survival in the ulcerogenic tumor syndrome approximated 50 per cent, with 40 per cent of those having proved malignancy living five years. Evidence of hyperparathyroidism is relatively common in association with both the ulcerogenic and the diarrheogenic tumor syndromes. The association may by a result of a congenital abnormality, metabolic alkalosis, or a direct effect of the islet cell tumor. Parathyroidectomy may be indicated when both the serum calcium and parathormone levels are elevated in the presence of borderline fasting gastrin levels. The latter may return to normal after parathyroidectomy. The evidence of hyperparathyroidism closely parallels the episodes of diarrhea in the diarrheogenic syndrome, and hyperparathyroidism may regress spontaneously after total removal of the pancreatic tumor. Just as routine calcium determinations made the diagnosis of hyperparathyroidism more commonplace, it is suggested that the gastrointestinal syndromes associated with islet cell tumor would receive wider recognition if radioimmunoassays for gastrin as well as secretin, and the other secretin-like polypeptides, were carried out routinely.

Topics: Adenoma, Islet Cell; Age Factors; Celiac Disease; Diagnosis, Differential; Diarrhea; Duodenal Neoplasms; Follow-Up Studies; Gastrins; Humans; Hyperparathyroidism; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Hormones; Pancreatic Neoplasms; Preoperative Care; Secretin; Zollinger-Ellison Syndrome

Topics: Adrenocorticotropic Hormone; Calcitonin; Calcium; Feedback; Gastrins; Gastrointestinal Hormones; Hypercalcemia; Hypocalcemia; Melanocyte-Stimulating Hormones; Pancreatic Neoplasms; Thyroid Gland; Zollinger-Ellison Syndrome

Gastric acid secretion by the parietal cell is a single digestive process involving a continuous interplay between nervous and hormonal stimuli. Gastric acid hypersecretion and hypergastrinemia may represent pathologic disturbance of the normal "gastric phase" of acid secretion (excluded antrum syndrome) or abnormal gastrin secretion from a nongastric source as in the Zollinger-Ellison syndrome. Diagnosis of these two syndromes preoperatively is dependent on immunoassay for serum gastrin. A fall in serum gastrin level after the injection of secretin will distinguish the excluded antrum syndrome from the Zollinger-Ellison syndrome. Which hormone or hormones cause the acid hyposecretion of the watery diarrhea hypokalemia achlorhydria syndrome is still uncertain. Potential candidates include secretin, glucagon (alone or combined with gastrin), vasoactive intestinal peptide and gastric inhibitory polypeptide. Secretin has undergone trials as therapy in peptic ulcer whereas glucagon is under investigation for the treatment of acute pancreatitis because of its dual actions as (1) an enterogastrone and (2) an inhibitor of pancreatic secretion.

Topics: Animals; Calcium; Female; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Histamine H1 Antagonists; Humans; Immunoassay; Intestinal Mucosa; Peptic Ulcer; Pyloric Antrum; Rabbits; Secretin; Stimulation, Chemical; Stomach; Swine; Syndrome; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Amino Acids; Antibody Specificity; Calcium; Catecholamines; Circadian Rhythm; Food; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Half-Life; Humans; Hydrogen-Ion Concentration; Insulin; Intestinal Mucosa; Pancreas; Species Specificity; Structure-Activity Relationship; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Child; Diagnosis, Differential; Diarrhea; Digestive System; Endocrine System Diseases; Female; Gastrectomy; Gastrins; Humans; Intestinal Diseases; Jejunum; Male; Middle Aged; Multiple Endocrine Neoplasia; Radiography; Recurrence; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Esophagogastric Junction; Gastric Mucosa; Gastrins; Humans; Ileocecal Valve; Liver; Pancreas; Radioimmunoassay; Sphincter of Oddi; Stomach; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Age Factors; Aged; Alkalosis; Calcium; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Hyperparathyroidism, Secondary; Lymphatic Metastasis; Male; Middle Aged; Parathyroid Hormone; Recurrence; Vagotomy; Zollinger-Ellison Syndrome

There is evidence that under various physiological circumstances long-term adaptation of structure and function of the gut occurs. The mechanisms of these changes are not clear but gastro-intestinal hormones may be involved. In particular, gastrin which has been shown experimentally to stimulate growth and development of parts of the gut, probably has a role in maintaining the structure of the normal upper alimentary tract. Cholecystokinin may be of major importance in producing adaptive changes in the pancreas in response to dietary modifications and enteroglucagon is possibly concerned with maintaining a normal small intestinal structure. The importance of the 'trophic' action of gatrointestinal hormones is becoming more widely recognised and as new gastro-intestinal hormones become established, this aspect of their physiological importance as well as their acute effects, will deserve attention.

Topics: Animals; Cholecystokinin; DNA; Duodenum; Female; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Diseases; Intestine, Small; Kidney Failure, Chronic; Lactation; Pancreas; Pregnancy; Rats; Secretin; Starvation; Weaning; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Blood Glucose; Calcium; Endocrine System Diseases; Gastrins; Humans; Insulin; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Pheochromocytoma; Pituitary Neoplasms; Radioimmunoassay; Syndrome; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Duodenal Neoplasms; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Peptic Ulcer; Radiography; Radioimmunoassay; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Acute Kidney Injury; Adenoma, Islet Cell; Adult; Cholecystokinin; Dehydration; Diarrhea; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypercalcemia; Hypokalemia; Kidney Diseases; Male; Pancreatic Neoplasms; Protein Precursors; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Amino Acid Sequence; Animals; Catecholamines; Dehydration; Diarrhea; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Intestinal Mucosa; Peptic Ulcer; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Syndrome; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastric Acidity Determination; Gastrins; Glucagon; Humans; Islets of Langerhans; Pancreatic Neoplasms; Syndrome; Zollinger-Ellison Syndrome

Topics: Acetylcholine; Anemia, Pernicious; Atrophy; Calcium; Carcinoma; Catecholamines; Circadian Rhythm; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Diseases; Hormones, Ectopic; Humans; Ligation; Pancreatic Ducts; Secretin; Stimulation, Chemical; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Motility; Humans; Hydrogen-Ion Concentration; Hypertrophy; Intestinal Mucosa; Pepsin A; Secretory Rate; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Digestion; Enzyme Therapy; Fats; Gastric Juice; Gastrins; Gastrointestinal Hemorrhage; Gastrointestinal Hormones; Humans; Methods; Pancreas; Pancreatectomy; Pancreatic Diseases; Pancreatic Juice; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Angiography; Diarrhea; Gastrectomy; Gastric Acidity Determination; Gastrins; Humans; Hypokalemia; Islets of Langerhans; Pancreas; Recurrence; Zollinger-Ellison Syndrome

Topics: Angiography; Biological Assay; Diarrhea; Duodenum; Endocrine System Diseases; Gastrectomy; Gastric Juice; Gastrins; Humans; Intestinal Neoplasms; Islets of Langerhans; Malabsorption Syndromes; Pancreatic Neoplasms; Peptic Ulcer; Prognosis; Radioimmunoassay; Stomach; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Insulin Secretion; Intestinal Mucosa; Pancreatic Hormones; Peptides; Secretin; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Dogs; Duodenal Ulcer; Esophagus; Gallbladder; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Pancreatic Juice; Secretin; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Vagotomy; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Animals; Cholecystokinin; Dogs; Duodenum; Fluorescent Antibody Technique; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Insulin Secretion; Intestinal Mucosa; Peptides; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Animals; Cats; Chronic Disease; Creatinine; Dogs; Duodenal Ulcer; Esophageal Achalasia; Esophageal Diseases; Gastric Mucosa; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Peptic Ulcer; Pyloric Antrum; Rats; Scleroderma, Localized; Stomach Neoplasms; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Angiography; Antacids; Celiac Disease; Diarrhea; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Malabsorption Syndromes; Pancreatic Neoplasms; Physical Examination; Radioimmunoassay; Radionuclide Imaging; Zollinger-Ellison Syndrome

Topics: Acetazolamide; Amphotericin B; Animals; Cholera; Cyclic AMP; Diarrhea; Dogs; Duodenum; Escherichia coli; Ethacrynic Acid; Fluorescent Antibody Technique; Gastrins; Humans; Intestinal Absorption; Intestinal Mucosa; Jejunum; Models, Biological; Peptides; Rabbits; Rats; Sodium; Toxins, Biological; Ultrafiltration; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastrins; Heparin; Humans; Intestine, Small; Pancreas; Zollinger-Ellison Syndrome

Topics: Dietary Proteins; Duodenal Ulcer; Feedback; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Peptic Ulcer; Radioimmunoassay; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Digestion; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Humans; Intestine, Small; Pancreas; Paraneoplastic Endocrine Syndromes; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Anemia, Pernicious; Chronic Disease; Duodenal Ulcer; Duodenum; Esophagus; Feedback; Gastric Juice; Gastrins; Gastritis; Gastrointestinal Motility; Humans; Intestinal Mucosa; Jejunum; Muscle Tonus; Pancreas; Pyloric Antrum; Radioimmunoassay; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Adenoma; Diagnosis, Differential; Gastrectomy; Gastric Juice; Gastrins; Humans; Neoplasm Metastasis; Peptic Ulcer; Radioimmunoassay; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Age Factors; Anemia, Pernicious; Antigen-Antibody Reactions; Antigens, Neoplasm; Cholecystokinin; Cross Reactions; Digestive System Physiological Phenomena; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hepatitis B Antigens; Hormones; Humans; Hyperglycemia; Insulin; Methods; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Afferent Loop Syndrome; Deglutition Disorders; Diet Therapy; Dumping Syndrome; Gastric Acidity Determination; Gastrins; Gastroenterostomy; Gastroscopy; Humans; Hyperparathyroidism; Malabsorption Syndromes; Pentagastrin; Peptic Ulcer; Postgastrectomy Syndromes; Postoperative Complications; Stomach; Stomach Ulcer; Sutures; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Age Factors; Body Weight; Diagnosis, Differential; Duodenal Ulcer; Ethnicity; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Male; Methods; Pentagastrin; Sex Factors; Stomach Diseases; Stomach Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastritis; Humans; Research; Zollinger-Ellison Syndrome

Topics: Bile; Gallbladder; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Histamine Release; Humans; Intestinal Mucosa; Intrinsic Factor; Muscle, Smooth; Pancreas; Pepsin A; Peptic Ulcer; Pylorus; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Blood Glucose; Diagnosis, Differential; Gastrins; Glucose Tolerance Test; Humans; Hyperparathyroidism; Insulin; Pancreatic Neoplasms; Parathyroid Neoplasms; Radioimmunoassay; Tolbutamide; Zollinger-Ellison Syndrome

Topics: Celiac Disease; Cholecystokinin; Digestion; Gastrins; Gastrointestinal Hormones; Homeostasis; Humans; Postgastrectomy Syndromes; Secretin; Vagotomy; Zollinger-Ellison Syndrome

Topics: Animals; Diarrhea; Gastrins; Gastrointestinal Motility; Gastrointestinal Neoplasms; Hormones, Ectopic; Humans; Intestinal Absorption; Zollinger-Ellison Syndrome

Topics: Antibodies; Duodenal Ulcer; Female; Gastrins; Humans; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Duodenal Ulcer; Feedback; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Absorption; Neurosecretory Systems; Pancreas; Peptic Ulcer; Secretin; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Acetylcholine; Achlorhydria; Adenoma; Anemia, Pernicious; Atrophy; Duodenal Ulcer; Endocrine System Diseases; Gastrectomy; Gastric Juice; Gastric Mucins; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Intrinsic Factor; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Duodenal Neoplasms; Female; Gastrectomy; Gastrins; Humans; Male; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Anura; Cats; Chemical Phenomena; Chemistry; Dogs; Gastric Juice; Gastric Mucosa; Gastrins; Guinea Pigs; Histamine Release; Humans; Rabbits; Rats; Zollinger-Ellison Syndrome

Topics: Acute Disease; Adenoma, Islet Cell; Cholecystokinin; Chronic Disease; Gastrins; Humans; Methods; Pancreas; Pancreas Transplantation; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Radiography; Secretin; Transplantation, Homologous; Zollinger-Ellison Syndrome

Topics: Animals; Depression, Chemical; Dietary Fats; Digestion; Digestive System; Gastrins; Gastrointestinal Diseases; Humans; Intestinal Absorption; Intestinal Mucosa; Malabsorption Syndromes; Stimulation, Chemical; Vitamin B 12; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Antibodies; Biological Assay; Gastrins; Humans; Immune Sera; Methods; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Anemia, Pernicious; Animals; Antibodies; Antibody Formation; Chemical Phenomena; Chemistry; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Humans; Peptic Ulcer; Rabbits; Species Specificity; Swine; Zollinger-Ellison Syndrome

Topics: Animals; Antibodies; Antibody Formation; Cholecystokinin; Cross Reactions; Gastrins; Guinea Pigs; Humans; Rabbits; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Gastric Acidity Determination; Gastric Juice; Gastrins; Gastrointestinal Hormones; Histamine; Humans; Male; Middle Aged; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Chemical Phenomena; Chemistry; Drug Synergism; Gallbladder; Gastric Juice; Gastrins; Gastrointestinal Motility; Histamine; Homeostasis; Humans; Liver; Pancreas; Stomach; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Gastric Acidity Determination; Gastric Juice; Gastrins; Gastritis; Histamine; Humans; Inhalation; Intubation, Gastrointestinal; Methods; Peptic Ulcer; Radio; Radioisotopes; Radionuclide Imaging; Stomach; Stomach Neoplasms; Technetium; Vagotomy; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Anemia, Pernicious; Animals; Cats; Cattle; Dogs; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Radioimmunoassay; Receptors, Drug; Sheep; Swine; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Intestine, Small; Jejunum; Male; Middle Aged; Neoplasm Metastasis; Radiography; Radioimmunoassay; Ulcer; Zollinger-Ellison Syndrome

Topics: 5-Hydroxytryptophan; Adenoma; Adenoma, Islet Cell; Adrenocorticotropic Hormone; Calcitonin; Catecholamines; Corticosterone; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Kinins; Pancreas; Pancreatic Neoplasms; Peptides; Prostaglandins; Secretin; Thyrotropin; Vasopressins; Zollinger-Ellison Syndrome

Topics: Acetylcholine; Animals; Anura; Biological Assay; Cats; Cattle; Culture Techniques; Dogs; Gastric Juice; Gastric Mucosa; Gastrins; Guinea Pigs; Histamine; Humans; Pancreas; Pancreatic Juice; Pepsin A; Radioimmunoassay; Rats; Sharks; Stimulation, Chemical; Stomach; Swine; Vagotomy; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Diarrhea; Digestive System; Fasting; Gastrins; Glucagon; Glucose; Glucose Tolerance Test; Humans; Hypoglycemia; Hypokalemia; Leucine; Pancreatic Neoplasms; Tolbutamide; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Gastrins; Humans; Zollinger-Ellison Syndrome

Topics: Animals; Dogs; Gastric Mucosa; Gastrins; Humans; Liver Cirrhosis; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastric Mucosa; Gastrins; Histocytochemistry; Hormones, Ectopic; Humans; Intestinal Mucosa; Microscopy, Electron; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Animals; Dogs; Gastric Juice; Gastrins; Humans; Sheep; Stomach; Swine; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Animals; Dogs; Gastric Juice; Gastrins; Pancreatic Juice; Pepsin A; Research; Zollinger-Ellison Syndrome

Topics: Antacids; Blood Circulation; Cryosurgery; Duodenal Ulcer; Electrolytes; Gastric Juice; Gastrins; Gastroenterostomy; Gonadal Steroid Hormones; Humans; Insulin; Pancreas; Pathology; Pepsin A; Peptic Ulcer; Pharmacology; Pylorus; Radiation Effects; Radiotherapy; Research; Stomach Ulcer; Stress, Physiological; Vagotomy; Zollinger-Ellison Syndrome

To evaluate the clinical characteristics, response to treatment and outcome of Zollinger?Ellison syndrome (ZES)-like gastric acid hypersecretors.. Over a 20-year period, patients with gastric acid hypersecretion in the absence of ZES were enrolled in an open label prospective trial evaluating the efficacy of lansoprazole. Following baseline evaluations, patients were treated with escalating doses of lansoprazole based on the results of gastric acid analysis. Following stabilization, patients were followed on a 6 monthly basis with interval history, physical examination, endoscopy with gastric biopsies, gastric acid analysis, and laboratory studies.. The study group represented 21 patients (median age 47 years, 86% male, 91% Caucasian). Historically, complicated ulcer disease was frequent and symptoms had been present for a median of 10 years before study entry. All patients responded to lansoprazole (median dose 90 mg/day) with excellent control of gastric acid hypersecretion. Mucosal relapse was infrequent and no major complications developed while on therapy.. ZES-like gastric acid hypersecretion presents similarly to the classic syndrome. Lansoprazole titrated to gastric acid output is effective in healing mucosal disease and preventing relapse.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Biopsy; Drug Administration Schedule; Female; Follow-Up Studies; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Gastroscopy; Humans; Lansoprazole; Male; Middle Aged; Prospective Studies; Stomach; Stomach Ulcer; Treatment Outcome; Zollinger-Ellison Syndrome

In this open prospective study, the efficacy of pantoprazole in reducing gastric acid secretion in Zollinger-Ellison syndrome patients was compared to that obtained previously with other proton pump inhibitors.. Eleven male patients previously treated with omeprazole (n=7, mean dosage: 63 mg/day; range: 20-100 mg/day) or lansoprazole (n=4, mean dosage: 75 mg/day; range: 30-120 mg/day) were included. These patients underwent a 24-hour intragastric pH-metry, measurement of basal acid output and of serum gastrin first while receiving their usual therapy and second after 7 to 10 days of pantoprazole treatment at a mean dosage of 116 mg/day (range: 40-200 mg/day). Basal acid output was evaluated after each intragastric pH-metry, one hour before the next intake of proton pump inhibitor and a serum gastrin curve was determined according to 9 fixed time points.. One patient dropped out before the second intragastric pH-metry due to an adverse event (varicella) unrelated to pantoprazole and was reinvestigated thereafter. The median 24-h intragastric pH with pantoprazole was not significantly different than that with the other proton pump inhibitors (5.3 versus 4.6, respectively; P=0.90). Neither the median basal acid output values nor the median serum gastrin levels were significantly different between pantoprazole and the other proton pump inhibitors.. In these patients with the Zollinger-Ellison syndrome, pantoprazole was well tolerated and equally effective to the other proton pump inhibitors in terms of antisecretory potency.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Benzimidazoles; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Lansoprazole; Male; Omeprazole; Pantoprazole; Prospective Studies; Proton Pump Inhibitors; Sulfoxides; Time Factors; Zollinger-Ellison Syndrome

Although biologically-derived porcine secretin is approved for the diagnosis of Zollinger-Ellison Syndrome, it is no longer available in the United States. Pure human and porcine secretins have now been synthesized and new drug applications have been filed with the Federal Drug Administration (FDA).. In the current study we compared secretin testing results in six confirmed Zollinger-Ellison Syndrome patients using the biologically-derived product and both synthetic products (human and porcine) in a three-way, randomized, single-blind Latin-squares crossover study.. Using the FDA-approved criterion for positive secretin testing (i.e. a serum gastrin concentration increase of > 110 pg/mL), there was complete agreement between all three agents for all patients. With the more stringent NIH criterion (i.e. a serum gastrin concentration increase of > 200 pg/mL), positive results persisted in five out of six, six out of six and four out of six patients using biologically-derived secretin, synthetic porcine secretin, and synthetic human secretin, respectively (six out of six, six out of six and four out of six if a positive test was defined as a 50% increase in serum gastrin concentration). The time to peak serum gastrin concentration after secretin injection occurred within 15 min in all studies (in 94% by 10 min and in 77% by 5 min). Three-way comparisons of serum gastrin concentrations showed a single statistically significant difference (the change from baseline at 15 min between synthetic human and synthetic porcine secretin, P=0.0274). Statistically significant changes from baseline occurred at 1, 2 and 5 min for biologically-derived porcine secretin and at 2 and 5 min for both synthetic porcine and synthetic human secretin, in keeping with the expected time curve for positive tests. All three agents were well-tolerated.. These data suggest that either synthetic secretin product, when released onto the United States market, can be used to confirm Zollinger-Ellison Syndrome.

Topics: Adult; Aged; Animals; Cross-Over Studies; Female; Gastrins; Gastrointestinal Agents; Humans; Male; Middle Aged; Secretin; Swine; Zollinger-Ellison Syndrome

Gastric analysis is useful for diagnosing and monitoring the control of hypersecretory conditions and to distinguish appropriate from inappropriate causes of hypergastrinaemia. Pentagastrin, used to measure maximal acid output (MAO), is no longer available in the USA.. We examined the University of Pennsylvania Health System gastric analysis database, which includes demographic data, study indications, gastric analysis, and serum gastrin and secretin testing results according to referral indications, paying specific attention to discordant basal acid output (BAO) and MAO measurements.. One hundred and twenty-four gastric analyses were performed in 103 patients (42 males, mean age 47.5 years, 14 with prior acid-decreasing surgery). Recurrent ulceration or pain unresponsive to antisecretory therapy was the indication in 42 patients. Twelve were hypersecretory, including three each with isolated elevations of BAO or MAO. Hypergastrinaemia was the indication in 35 patients. Five were hypersecretory (four with Zollinger-Ellison syndrome), three had isolated MAO elevations and 16 were hypo- or achlorhydric, indicating appropriate hypergastrinaemia. Of the seven patients with isolated MAO elevations, two had clear benefit from the stimulated portion of the study (four additional patients had equivocal benefit).. Gastrin concentrations cannot be interpreted without knowledge of acid secretory capacity. MAO measurement has a small but significant benefit over measuring BAO alone.

Topics: Achlorhydria; Adolescent; Adult; Aged; Enzyme Inhibitors; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Proton Pump Inhibitors; Recurrence; Retrospective Studies; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Serum chromogranin A levels (CgA) are reported by some authors to be of clinical utility for assessing the presence or absence of a pancreatic endocrine tumor and tumor extent or growth. The aim of the current study was to assess this finding and compare the results with those from serum gastrin determinations (FSG) in a large cohort of patients with gastrinomas.. In 112 consecutive patients with the Zollinger-Ellison syndrome serum CgA and FSG levels were measured and correlated with disease activity, extent of disease, and the presence of multiple endocrine neoplasia type-1 (MEN-1) or gastric carcinoid tumors.. Serum CgA levels drawn on 2 consecutive days correlated closely (P < 0.00001) as did serum gastrin levels. Serum CgA levels correlated significantly with FSG levels (P < 0.00001). Serum CgA and FSG levels were significantly higher in patients with active disease than in disease free patients (P < 0.00001). The sensitivity for the presence of disease was higher for CgA compared with FSG (92% vs. 80%; P = 0.021). However, the specificity of CgA was 67%. Serum CgA levels were not significantly different in the four disease categories (stable extrahepatic disease, increasing extrahepatic disease, stable liver metastases, and increasing liver metastases). FSG levels were significantly lower in patients with stable extrahepatic disease compared with those with increasing extrahepatic disease. However, both tumor markers decreased significantly with a gastrinoma resection in five patients. The presence of MEN-1 or a gastric carcinoid tumor did not influence the results.. The results of the current study showed that serum CgA and FSG levels both are sensitive tumor markers for the detection of a gastrinoma; however, CgA levels have a relatively low specificity. Neither the magnitude of the serum CgA nor gastrin level correlated with tumor growth or tumor extent and therefore cannot be used to determine these variables. However, in contrast to some other studies, the results of the current study show that changes in serum CgA or gastrin in a given patient with time are related to the tumor extent and not to gastric mucosal changes due to hypergastrinemia.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoid Tumor; Chromogranin A; Chromogranins; Female; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Prospective Studies; Sensitivity and Specificity; Stomach Neoplasms; Zollinger-Ellison Syndrome

To evaluate the response of endocrine cells of the gastric oxyntic mucosa in hypergastrinaemic patients to either antrectomy or treatment with the somatostatin analogue octreotide.. (a) Two patients with enterochromaffin-like (ECL) cell carcinoid and chronic atrophic gastritis, treated with antrectomy; (b) four patients with Zollinger-Ellison syndrome, treated with octreotide.. Oxyntic endocrine cells were examined by ultrastructural morphometry on full thickness biopsy specimens taken: (a) before and four months after antrectomy, (b) before and after three months' treatment with octreotide 200 micrograms daily.. Both treatments induced prompt, significant reduction of gastrinaemia and a significant decrease of the volume density of the whole endocrine cell mass and of the cross sectional area of all nucleated endocrine cell profiles (antrectomy: -38%, p < 0.04 and -31%, p < 0.04, respectively; octreotide: -59%, < 0.007 and -26%, < 0.04, respectively). Assessment of the relative proportion of individual endocrine cell types showed a different response to antrectomy or octreotide. After antrectomy, in fact, only the volume fraction of ECL cells was significantly reduced, from 56.5% to 22.5% (-60%, p < 0.04). After octreotide treatment, in contrast, the proportion of all endocrine cell types remained remarkably constant, showing that all cell types took part in the observed overall decrease.. Postantrectomy reduction of oxyntic endocrine cells mostly reflects the withdrawal of the specific trophic stimulus of hypergastrinaemia on ECL cells. In contrast, the inhibitory response to octreotide seems to be exerted on virtually all types of oxyntic endocrine cells, probably reflecting a universal occurrence of somatostatin receptors.

Topics: Adult; Aged; Carcinoid Tumor; Female; Gastrins; Gastritis, Atrophic; Gastrointestinal Agents; Humans; Male; Microscopy, Electron; Middle Aged; Octreotide; Parietal Cells, Gastric; Pyloric Antrum; Stomach Diseases; Stomach Neoplasms; Zollinger-Ellison Syndrome

About 10% of patients with duodenal ulcers have marked gastric acid hypersecretion with basal acid output (BAO) of more than 15 mmol/h, which is in the range found in Zollinger-Ellison syndrome.. We report long-term, up to 4 years, prospective treatment using lansoprazole in nine male patients with duodenal ulcers and a BAO of more than 15 mmol/h whose results are compared with those in 10 male Zollinger-Ellison syndrome patients with intact stomachs reported in detail in an accompanying paper.. All 19 subjects, except one Zollinger-Ellison syndrome patient who had gastric and oesophageal ulcers, had a history of duodenal ulcers; 22% of those with gastric acid hypersecretion had oesophagitis compared with 60% of those with Zollinger-Ellison syndrome. Each subject had the dose of lansoprazole adjusted to give a BAO of less than 5 mmol/h. At 3-month intervals to 1 year, and then at 6-monthly intervals, basal and pentagastrin stimulated secretions were studied, in addition to gastroscopy with biopsy for gastric mucosal morphology. Basal and maximal acid and pepsin secretions were not different between gastric acid hypersecretion and Zollinger-Ellison syndrome patients before treatment. During treatment, BAO was reduced by over 90% to less than 2 mmol/h, while peak acid output was reduced by 70% in those with gastric acid hypersecretion and 90% in Zollinger-Ellison syndrome patients. Four gastric acid hypersecretion patients had relapses during treatment, three times in one patient and twice in another patient, but all responded to continued treatment with lansoprazole. Of the seven ulcer-related relapses in the gastric acid hypersecretion patients, four occurred with a BAO of less than 2 mmol/h and three with a BAO of 7.1-7.3 mmol/h; five of the seven relapses occurred in the absence of Helicobacter pylori. Lansoprazole remained effective at an average dose of approximately 70 mg/day, without causing any side-effects.. Lansoprazole is apparently safe and effective for treating hypersecretion, whether due to hypergastrinaemia (Zollinger-Ellison syndrome) or not (non-Zollinger-Ellison syndrome hypersecretors).

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Duodenal Ulcer; Enzyme Inhibitors; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Patient Dropouts; Prospective Studies; Proton Pump Inhibitors; Zollinger-Ellison Syndrome

Normalization of gastric secretion and cure of associated upper gastrointestinal lesions by resection of gastrinoma is possible in approximately 20% of patients with Zollinger-Ellison syndrome, leaving approximately 80% dependent on medical treatment with proton pump inhibitors for acid suppression.. Lansoprazole was given for 3-48 months (median 28 months) to 26 Zollinger-Ellison syndrome patients with peptic ulcer manifestations in all and oesophagitis in 13. Starting with 60 mg/day. the dose was individualized to lower basal acid output to less than 5 mmol/h for those with intact stomachs and less than 1 mmol/h in those who had prior gastrectomy or with oesophagitis. The patients were studied every 3 months for 1 year and then every 6 months with gastric analysis (basal and maximal acid and pepsin output) and endoscopy with biopsy for enterochromaffin-like (ECL) cells.. Lansoprazole inhibited basal acid output by 95%, pepsin output by 65% and remained effective at the initial mean (66 +/- 4.3 mg/day) or smaller doses (56 +/- 12 mg/day) at 48 months. Mucosal lesions healed and symptoms (ulcer-type pain, diarrhoea, heartburn, weight loss) resolved rapidly, usually within a few weeks. Serum gastrin and ECL cell populations, which were elevated before treatment, remained statistically unchanged but one of the three multiple endocrine neoplasia I (MEN-I) patients developed a small carcinoid. Of the three patients with metastatic gastrinoma at diagnosis one has died and one has progressed, while the third has had stable liver metastases for 26 years. Ulcer-type relapses occurred in three of the five post-gastrectomy patients, one with fatal jejunal ulcer perforation despite adequate acid suppression. No biochemical or clinical adverse events due to lansoprazole were encountered.. Lansoprazole effectively inhibits acid and pepsin secretion in Zollinger-Ellison syndrome patients without any demonstrated side-effects. Despite strict acid control, post-gastrectomy Zollinger-Ellison syndrome patients were more liable to ulcer relapse, while oesophagitis was not a marker for therapeutic difficulty.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Enzyme Inhibitors; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Patient Dropouts; Pentagastrin; Proton Pump Inhibitors; Zollinger-Ellison Syndrome

Patients referred to us with "positive" secretin tests and the diagnosis of Zollinger-Ellison syndrome were found to be achlorhydric. This observation led us to study prospectively the accuracy and precision of serum gastrin determinations from commercial laboratories. Synthetic gastrin (G17) was added to serum to achieve gastrin concentrations of 50, 100, 250, 500, 750, 1000, 3000, and 5000 pg/mL after subtraction of the basal value (24 pg/mL). Three aliquots of each concentration were analyzed by radioimmunoassay in our laboratory (Health Science Center at Brooklyn) and sent to four major commercial laboratories that perform 5000 to 25,000 gastrin assays per year. The reported gastrin concentrations of the triplicate samples demonstrate that many commercial laboratories failed to accurately measure gastrin. Commercial laboratories generally reported higher-than-actual gastrin concentrations in samples containing less than 500 pg/mL and lower-than-actual gastrin concentrations in samples containing more than 500 pg/mL. Of all aliquots containing 100 pg/mL or less, 14 of 24 samples (58%) were reported by commercial laboratories to contain elevated gastrin concentrations. At gastrin concentrations from 250 to 5000 pg/mL, the range of values (highest- to lowest-reported value for each concentration) was greater than 200 pg/mL in 62% of triplicate samples reported by commercial laboratories. These data indicate that determinations by some commercial laboratories lack the precision required to satisfy the current diagnostic criterion (a postsecretin rise from basal gastrin of 200 pg/mL or greater) for Zollinger-Ellison syndrome. Clinicians should be aware of this problem and obtain more basal serum gastrin samples to allow for an analysis of the range of baseline values prior to secretin injection.

Topics: Biomarkers; Diagnostic Errors; Gastrins; Humans; Laboratories; New York; Predictive Value of Tests; Prospective Studies; Zollinger-Ellison Syndrome

This paper aimed at evaluating the comparative efficacy of lansoprazole and omeprazole in reducing gastric acid secretion in patients suffering from Zollinger-Ellison syndrome.. Nine patients with non-resected gastrinoma(s) an previously well controlled by omeprazole (mean dosage 75 +/- 12.4 (SEM) mg/day; extremes: 20-160 mg/day) underwent 24-hour intragastric pH-metry, baseline acid output before next dosing and serum gastrin dosages, receiving their usual therapy and thereafter lansoprazole at a weight equivalent posology (mean dosage 81.6 +/- 12.5 (SEM) mg/day; extremes: 30-165 mg/day).. Lansoprazole maintained intragastric pH and basal acid output at therapeutic levels, but a discrete reacidification, that deserves confirmation on a larger group of patients, was observed between the meals.. The possible long-term benefit of this phenomenon, especially on gastrinemia and the fundic ECL-cells density and gastric bacterial content, remains to be evaluated.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Lansoprazole; Male; Middle Aged; Omeprazole; Zollinger-Ellison Syndrome

The effects of three months of treatment with octreotide on gastric acid hypersecretion induced by hypergastrinaemia were investigated in patients with Zollinger-Ellison syndrome (n = 5) or antral G-cell hyperfunction (n = 4). Gastric acid secretion, fasting plasma gastrin concentrations and clinical findings were examined, and a morphometrical analysis of oxyntic endocrine cells was performed.. Administration of octreotide 100 mcg b.d. subcutaneously significantly decreased the volume density of argyrophil cells (P < 0.05) as well as basal and pentagastrin-stimulated acid secretion (P < 0.05). Although partial or complete loss of inhibition was found in most patients after 3 months, gastrin levels were decreased during the first 2 months of treatment (P < 0.05). Fundic D-cells were not affected by treatment. Positive correlations were observed between volume density of argyrophil cells and basal acid output (r = 0.65); plasma gastrin and basal acid output (r = 0.74); plasma gastrin concentrations and volume density of argyrophil cells (r = 0.80).. These results support the important role of the enterochromaffin-like cell in maintaining acid secretion, and indicate a specific role for octreotide in the therapy of gastric acid hypersecretion associated with hypergastrinaemic diseases.

Topics: Administration, Oral; Adult; Cell Count; Enterochromaffin Cells; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Octreotide; Pyloric Antrum; Somatostatin; Zollinger-Ellison Syndrome

H+, K(+)-ATPase inhibitors such as omeprazole are the antisecretory agents of choice for the management of gastric acid hypersecretory states, including the Zollinger-Ellison syndrome. However, long-term follow-up data on the overall efficacy and safety of these agents in large numbers of patients are lacking. In the current study we examined the long-term efficacy and safety of omeprazole in 116 patients with Zollinger-Ellison syndrome treated with oral omeprazole at a single centre for up to 114 months (mean +/- S.E.M. = 38 +/- 3 months). The initial omeprazole maintenance dose was established according to the acute upward dose titration method in 89/116 patients (77%). Gastric acid output was effectively controlled using 60 mg of omeprazole once daily in 41/89 patients (46%) and 22/89 patients (25%) required twice daily omeprazole therapy. The mean ranitidine equivalent dose for patients who required 60 mg omeprazole once daily (2.5 +/- 0.2 g/day) was significantly lower than the mean ranitidine equivalent dose for patients who required more than 60 mg omeprazole once daily (4.3 +/- 0.3 g/day). Long-term omeprazole maintenance therapy was discontinued in 36/116 patients (31%) but in no cases was discontinuation due either to drug-induced side-effects or uncontrolled gastric acid output. Fasting serum gastrin levels were significantly elevated above pre-treatment levels at only one time point during follow-up and were likely due to tumour growth rather than a drug effect. The final long-term omeprazole maintenance doses were lower than the initial doses but correlated closely with the pre-omeprazole basal acid output (r = 0.41, P < 0.001) and ranitidine equivalent dose requirements (r = 0.49, P < 0.001). We conclude that omeprazole effectively and safely controls gastric acid hypersecretion in all patients with Zollinger-Ellison syndrome for up to nine years without evidence by tachyphylaxis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Omeprazole; Prospective Studies; Ranitidine; Zollinger-Ellison Syndrome

Metastatic gastrinoma is becoming increasingly recognized in patients with Zollinger-Ellison Syndrome. The mean 5-year survival of these patients is < 20%. Chemotherapeutic regimens are of limited benefit. The aim of this study was to evaluate the use of interferon in these patients because a preliminary report suggested it might be effective.. The efficacy and toxicity of interferon was assessed in 13 consecutive Zollinger-Ellison syndrome patients with liver metastases. Patients were treated with human recombinant alpha interferon (5 million IU, subcutaneously [SC]) daily and followed up at 3-month intervals with multiple imaging studies. At each follow-up, toxicity of therapy was assessed and fasting serum gastrin concentrations were obtained.. No patient showed a reduction in tumor size at any follow-up. One patient died after 2 months. At 6 months, six patients (46%) had stable tumor size in the liver, although new bone metastases developed in one patient. Three patients showed stable disease for up to 21 months. Changes in serum gastrin correlated with tumor response at 6 months. All patients developed some side effects of therapy. Thirty-one percent required dose reduction, and one patient (8%) had to have interferon therapy interrupted briefly.. These results fail to define a therapeutic role for interferon in the treatment of metastatic gastrinoma.

Topics: Adult; Female; Follow-Up Studies; Gastrinoma; Gastrins; Humans; Interferon-alpha; Liver Neoplasms; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Zollinger-Ellison Syndrome

The long-term safety and efficacy of lansoprazole were studied in 21 patients with Zollinger-Ellison syndrome. The initial maintenance dose was determined by acid inhibition studies. In all patients lansoprazole controlled gastric acid hypersecretion and peptic symptoms in both the short and long term. Patients were treated for a mean of 31 months (range 1-43 months) with all but 4 patients followed for > 18 months. The mean initial dose was 60 mg/day, with 2 patients requiring a twice daily dose and the others a single daily dose. During long-term treatment 6 patients required an increased dosage, 5 within the first year. Long-term maintenance doses were reduced in 5 of the 6 patients in whom this was attempted. No changes in serum gastrin concentration, haematological parameters, liver function studies or other biochemical parameters occurred due to lansoprazole. No patient developed a gastric carcinoid tumour while being treated with lansoprazole. These results demonstrate that long-term treatment with lansoprazole is both safe and effective in patients with Zollinger-Ellison syndrome, and suggest that this drug will be useful in such patients. Furthermore, maintenance doses of lansoprazole, determined by the currently recommended method of acute acid titration studies in patients with Zollinger-Ellison syndrome, are too high.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Alanine Transaminase; Anti-Ulcer Agents; Aspartate Aminotransferases; Drug Administration Schedule; Fasting; Female; Follow-Up Studies; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Prospective Studies; Zollinger-Ellison Syndrome

Since 1980, 73 patients with Zollinger-Ellison syndrome (ZES) without radiographic evidence of liver metastases were studied on a prospective protocol including medical management of gastric acid hypersecretion, extensive radiographic tumor localization, and exploratory surgery to find and resect gastrinoma for potential cure. Each patient had gastric acid hypersecretion effectively controlled with either H2-blockers or omeprazole. Patients were divided prospectively into two groups, with all patients undergoing the same preoperative localization studies and extensive laparotomy. In contrast to group 1 (1980-1986) (36 patients), group 2 (1987-Oct. 1990) (37 patients) also underwent additional procedures (transillumination and duodenotomy) at surgery to find duodenal gastrinomas. Preoperative imaging studies localized tumor in 38 (52%) patients, and portal venous sampling for gastrin determinations was positive in 49 (67%) patients. Gastrinomas were found and resected in 57 (78%) patients. Significantly more gastrinomas (92% of patients) were found in group 2 than in group 1 patients (64%) (p less than 0.01). This increase was due to increased numbers of duodenal gastrinomas in group 2 than in group 1 patients (43% versus 11%; p less than 0.01). The increased ability to find duodenal gastrinomas did not significantly improve the immediate disease-free rate, which was 58% for all patients. Duodenal primary gastrinomas were found to have a significantly greater incidence of metastases (55%) and a significantly shorter disease-free interval (12 months) than pancreatic gastrinomas (22% and 84 months, respectively) suggesting that duodenal gastrinomas may be more malignant and not more frequently curable than pancreatic gastrinomas. Operations were performed with no deaths and 11% morbidity rate. Long-term follow-up showed that 50% of patients initially rendered disease free would develop recurrent disease by 5 years. Survival was excellent for all patients, and none died of malignant spread of the tumor or uncontrolled peptic ulcer disease, with a mean follow-up of 5 years. This finding is in contrast to patients who presented with metastatic disease on imaging studies and had a 20% 5-year survival rate. This study suggests that all patients with localized sporadic ZES can have the gastric acid hypersecretion managed medically, that overall survival of these patients is excellent, most (78%) can have all gastrinoma found and resected, and some (30%) will be cu

Topics: Adult; Aged; Anti-Ulcer Agents; Combined Modality Therapy; Duodenal Neoplasms; Female; Follow-Up Studies; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Laparoscopy; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Postoperative Complications; Prospective Studies; Survival Rate; Time Factors; Treatment Outcome; Zollinger-Ellison Syndrome

The chronic hypergastrinemia in diseases such as the Zollinger-Ellison syndrome has trophic effects on the gastric mucosa, causing increased parietal cell mass reflected by increased maximal acid output (MAO) and basal acid output (BAO). The time course for the development of these gastric changes in humans is unknown, and controversy exists regarding whether reversal of the hypergastrinemia results in rapid normalization of gastric secretory function. To address these uncertainties, gastric secretory function was prospectively evaluated in 20 patients with the Zollinger-Ellison syndrome undergoing successful curative resection of gastrinoma. Each patient had gastric acid measurements, imaging studies, fasting serum gastrin and secretin provocative testing preoperatively, postoperatively at 3-6 months, and yearly thereafter. Preoperative mean BAO was 39 mEq/h, MAO 56 mEq/h, BAO-MAO ratio 0.73, and fasting gastrin output 1020 pg/mL. All patients were evaluated at 6 months, 17 at 1 year, 15 at 2 years, 13 at 3 years, and 9 at 4 years. By 3-6 months, MAO decreased by 50% in men (mean, 30 mEq/h) and by 35% in women (mean, 29 mEq/h) and then remained relatively unchanged for up to 4 years. Before surgery, 14 of 20 patients (70%) had an elevated MAO, whereas 4 years after resection, none of 9 patients had elevated levels. By 3-6 months, BAO decreased by 75% and remained unchanged for up to 4 years. At 3-6 months, 56% of patients were mild hypersecretors and 67% remained hypersecretors up to 4 years. Preoperatively, the BAO-MAO ratio was elevated in 16 of 20 patients (80%); postoperatively, only 5 of 18 patients (28%) at 3-6 months, 2 of 15 (13%) at 1 year, and 2 of 10 (20%) at 4 years continued to have elevated ratios. Preoperatively, the mean ranitidine dose was 1597 mg/day, whereas after surgery the mean dose was 535 mg/day at 3-6 months and approximately 300 mg/day at 1-4 years with 8 patients requiring no antisecretory drug. These results show that the trophic effects of chronic hypergastrinemia are, in general, rapidly reversible with a 50% decrease in MAO within 3-6 months of cure. Similarly, BAO decreased by 75% within 3-6 months. Despite these decreases, careful monitoring of acid secretion is required after reversal of the chronic hypergastrinemia in diseases such as the Zollinger-Ellison syndrome, because 55% of patients at 3-6 months and up to 67% at 4 years continue to remain mild hypersecretors and require low doses of antisecretory drugs.

Topics: Adult; Aged; Cimetidine; Dose-Response Relationship, Drug; Duodenal Neoplasms; Famotidine; Female; Follow-Up Studies; Gastric Acid; Gastric Mucosa; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Omeprazole; Pancreatic Neoplasms; Postoperative Period; Prospective Studies; Ranitidine; Sex Factors; Time Factors; Zollinger-Ellison Syndrome

As calcium is important in the regulation of gastric acid secretion and gastrin release, we have examined the effect of the calcium antagonist nifedipine on these processes in man. Nifedipine 30 mg orally inhibited basal acid output by 37% (p less than 0.025) and that stimulated by low infusion rates of pentagastrin--that is, 0.031 and 0.062 microgram/kg/h by 44% (p = 0.05) and 39% (p less than 0.02) respectively. On increasing the pentagastrin infusion rate the inhibition was surmounted suggesting it was competitive in type. Nifedipine did not affect basal or Oxo meal stimulated gastrin concentrations in normal volunteers nor did it affect resting serum gastrin or calcium stimulated increase in gastrin in a single patient with Zollinger-Ellison syndrome. These findings are consistent with the transmembrane flux of calcium ions being involved in basal and pentagastrin stimulated acid secretion in man.

Topics: Adult; Calcium; Clinical Trials as Topic; Double-Blind Method; Gastric Acid; Gastrins; Humans; Male; Nifedipine; Pentagastrin; Random Allocation; Zollinger-Ellison Syndrome

GIH secretin bolus (2 CU/kg) and infusion (3 CU/kg/h) have been randomly compared in 9 ZES patients and 10 age-matched DU patients. Serum gastrin and gastric acid variations were studied before and after either mode of secretin administration in the same individuals. Plasma secretin modifications were monitored in parallel. In both ZES and DU, secretin bolus and infusion induced similar gastrin responses (maximal changes and integrated responses). However, secretin infusion had a greater effect on acid output than bolus: larger inhibition in DU and larger increase in ZES. The additive diagnostic value of gastric acid secretion study during a secretin provocation test, as already reported, favors the use of 3 CU/kg/h secretin infusion over that of 2 CU/kg secretin bolus.

Topics: Administration, Oral; Adult; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Infusions, Parenteral; Secretin; Secretory Rate; Zollinger-Ellison Syndrome

We studied the effect of intravenous administration of a gastrin-receptor antagonist (proglumide) on gastric acid secretion and serum gastrin in three patients with Zollinger-Ellison syndrome. Proglumide administered as a bolus injection (50 mg/kg) or as an infusion (50 mg/kg hour and 100 mg/kg hour) or as a combination of bolus injection and infusion (50 mg/kg I.V. followed by 50 mg/kg hour) inhibited gastric acid secretion by 13-62%. Cimetidine (2 mg/kg I.V. followed by 2 mg/kg hour) inhibited gastric acid secretion by 83-86%. Neither proglumide nor cimetidine significantly influenced serum gastrin concentrations. We conclude that proglumide is a relatively weak inhibitor of gastric acid secretion in patients with the Zollinger-Ellison syndrome.

Topics: Adult; Cimetidine; Female; Gastric Acid; Gastrins; Glutamine; Humans; Male; Middle Aged; Proglumide; Zollinger-Ellison Syndrome

A prospective study of the value of secretin, calcium, and meal gastrin challenge tests for the diagnosis of gastrinoma indicated that the secretin test may be valuable. The calcium test was equally valuable, but it cannot be recommended as enthusiastically because it is time-consuming and may cause side effects. New criteria for interpretation of these tests were based on peak responses to the challenge. Further, the study revealed that patients with hypochlorhydria and hypergastrinemia could be identified without the use of gastric analysis. This prospective study reflects the current pattern of clinical practice at a referral institution where patients with gastrinoma, an unusual condition, are seen with regularity. The criteria we propose for interpretation of these tests are simple and could be applied to individual patients in whom a gastrinoma is suspected.

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Diet; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Secretin; Sugar Acids; Zollinger-Ellison Syndrome

Oral 16,16-dimethyl prostaglandin E2 is a potent inhibitor of meal-stimulated gastric acid secretion and gastrin release in humans. Experiments were performed in 5 patients with inactive duodenal ulcer to determine the effect of graded doses of intravenous 16,16-dimethyl PGE2 on meal-stimulated gastric acid secretion and gastrin release to demonstrate whether it is necessary for 16-16-dimethyl PGE2 to come into direct luminal contact with the oxyntic and antral gland portions of the stomach to produce its inhibitory effects. All doses of 16,16-dimethyl PGE2, between 0.01 and 0.1 microgram/kg i.v. and between 0.01 and 1.0 microgram/kg orally produced significant postprandial inhibitory effects on both gastric acid secretion and gastrin release as compared with saline control. 0.1 microgram/kg of intravenous of 1 microgram/kg of oral 16,16-dimethyl PGE2 inhibited meal-stimulated acid secretion and gastrin by 80-90%. In 6 unoperated Zollinger-Ellison syndrome patients, 1 microgram/kg of oral 16,16-dimethyl PGE2 significantly inhibited fasting gastric acid hypersecretion by approximately 85% without significantly altering serum gastrin. Each of the oral doses of 16,16-dimethyl PGE2 (0.01-1 microgram/kg) were without untoward effect, as were intravenous doses of 0.01-01 microgram/kg. Maximal inhibition of acid secretion was found with 0.1 microgram/kg 16,16-dimethyl PGE2 i.v. as compared with 1.0 microgram/kg orally. Since 16,16-dimethyl PGE2, whether given orally or intravenously, is a potent inhibitor of both gastric acid secretion and meal-stimulated gastrin release, without apparent untoward side effects, clinical trials with 16,16-dimethyl PGE2 are indicated in patients with acid peptic disease.

Topics: 16,16-Dimethylprostaglandin E2; Administration, Oral; Adult; Aged; Duodenal Ulcer; Food; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Male; Middle Aged; Prostaglandins E, Synthetic; Zollinger-Ellison Syndrome

Calcitonin (CT) inhibits basal and pentagastrin stimulated gastric acid and pepsin secretion by 60 to 70% when CT is infused over a short period of time. Vagal and histamine-mediated stimulations are less diminished. A long-term infusion of CT inhibits persitently basal and pentagastrin-stimulated acid and pepsin secretion over more than 24 hours in patients with duodenal ulcer, stress bleeding and Zollinger-Ellison-Syndrome. To date, the therapeutic efficiency of CT in gastroduodenal bleeding has not been evaluated in a controlled trial. CT inhibits gastric secretion also after oral application. In an endoscopically controlled double blind trial we were not able to demonstrate a significant benefit of oral CT in patients with gastric ulcer. In ulcer bleeding CT does not apear reasonable in comparison with histamine-H2-receptor antagonists which apparently is more efficient and less costly.

Topics: Calcitonin; Clinical Trials as Topic; Double-Blind Method; Gastric Juice; Gastrins; Humans; Peptic Ulcer; Zollinger-Ellison Syndrome

The treatment of gastric ulcer by the H2-receptor-antagonist Cimetidine results in an ulcer healing rate of 60 to 80% during a 4 to 6 weeks therapy cure. In most studies Cimetidine is superior to placebo or equipotent to a high dose antacid regimen, the latter being accepted to be of beneficial effect on ulcer healing. In the Zollinger-Ellison-syndrome Cimetidine inhibits largely gastric acid hypersecretion and represents for the first time a true alternative to total gastrectomy.

Topics: Antacids; Carbenoxolone; Cimetidine; Double-Blind Method; Gastric Juice; Gastric Mucosa; Gastrins; Guanidines; Humans; Placebos; Stomach Ulcer; Zollinger-Ellison Syndrome

To evaluate the usefulness of provocation tests in the diagnosis of the Zollinger-Ellison (ZE) syndrome stimulation tests with calcium, 15 mg/kg. 3 h, and secretin GIH, 1 U/kg.30 s, were performed in 15 patients with histologically proven or suspected ZE syndrome. Nine of these 15 patients were without previous gastric surgery and in them meal stimulated serum gastrin levels were measured as well. These tests were also performed in normal subjects and in patients with duodenal ulcer, antrectomy, total gastrectomy, and achlorhydria. All tests were considered to be positive if a more than 50% increase in serum gastrin was found. The results indicate that secretin stimulation is the provocation test of first choice in the diagnosis of this syndrome. This test is most valuable for the following reasons: (1) there were few (two out of 15) false-negative test results in ZE patients; (2) there were no false-positive tests in 69 patients without gastrinoma; (3) it was easy and quick to perform; and (4) there were no adverse reactions. The two ZE patients with negative secretin stimulation tests had negative calcium provocation tests as well, in spite of histologically proven gastrinoma. In 11 patients with suspected or proven ZE syndrome and basal serum gastrin levels of less than 1000 pg/ml a rather good correlation (r = 0-841; P less than 0-01) was found between the percental increase in serum gastrin after stimulation by calcium and secretin. Meal stimulated serum gastrin levels are helpful only in patients without previous gastric surgery.

Topics: Adolescent; Adult; Aged; Calcium; Clinical Trials as Topic; Eating; Female; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

The histamine H2-receptor antagonist metiamide is an inhibitor of endogenous and stimulated gastric-acid secretion. It appears to have therapeutic possibilities in duodenal-ulcer disease. Three patients exhibiting the Zollinger-Ellison syndrome have been treated with this drug for six months or more. Rapid symptomatic improvement occurred in each case, followed by ulcer healing. There were also reductions in gastric secretion and consistent changes in the fasting serum-gastrin concentration. On patient relapsed temporarily during therapy. There have been no side effects. It is concluded that, in the short term, metiamide is of benefit in the Zollinger-Ellison syndrome.

Topics: Adult; Clinical Trials as Topic; Drug Evaluation; Female; Gastric Juice; Gastrins; Humans; Male; Metiamide; Middle Aged; Remission, Spontaneous; Thiourea; Zollinger-Ellison Syndrome

Topics: Acromegaly; Adult; Anemia, Pernicious; Blood Glucose; Fasting; Female; Food; Gastric Juice; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Infusions, Parenteral; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides; Radioimmunoassay; Time Factors; Zollinger-Ellison Syndrome

Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited endocrine cancer syndrome. Multiple gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) affect 30% to 80% of MEN1 patients, with the most common functioning GEP-NET being gastrinoma. Biochemical identification of hypergastrinemia may help to recognize the presence of gastrinomas before they are detectable by instrumental screening, enabling early diagnosis and start of therapy, preferably before tumor progression and metastases occurrence.. Evaluate the effectiveness of secretin stimulation test to precociously diagnose the presence of gastrin-secreting tumors.. Results of secretin stimulation tests, performed between 1991 and February 2020, were retrospectively analyzed, as aggregate, in a cohort of MEN1 patients with GEP-NETs.. Data were extracted from the MEN1 Florentine database.. The study included 72 MEN1 patients with GEP-NETs who underwent a secretin stimulation test for the evaluation of gastrin secretion.. A positive secretin stimulation test was assumed with a difference between basal fasting serum gastrin (FSG) and the maximum stimulated value of gastrin over 120 pg/mL.. The secretin stimulation test showed a secretin-induced hypergastrinemia in 27.8% (20/72) of patients with GEP-NETs, and a positive test in 18 cases. The test allowed the identification of a positively stimulated hypergastrinemia in 75.0% (3/4) of patients who presented a basal FSG within the normal range.. Diagnosis of gastrinoma is complex, difficult, and controversial. Results of this study confirm that a positive secretin stimulation test allows early diagnosis of gastrinomas, even in the presence of borderline or normal levels of nonstimulated FSG.

Topics: Early Detection of Cancer; Gastrinoma; Gastrins; Humans; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Retrospective Studies; Secretin; Zollinger-Ellison Syndrome

Topics: Gastrins; Gastroesophageal Reflux; Humans; Zollinger-Ellison Syndrome

Neurofibromatosis type (NF-1) is an autosomal dominant disorder characterized predominantly by neurocutaneous manifestations. Involvement of the gastrointestinal tract is uncommon but is associated with a significant risk of malignancy. There are a handful of case reports linking NF-1 with pancreatic neuroendocrine tumors; these include gastrin-secreting variants with the attendant Zollinger-Ellison syndrome. We present the case of a 52-year-old lady who presented with recurrent peptic ulceration and diarrhea. Serum gastrin levels were elevated and magnetic resonance imaging demonstrated the presence of a pancreatic lesion with multiple liver metastases. The lesion was moderately fludeoxyglucose avid on positron emission tomography-computed tomography. Endoscopic ultrasonography-guided sampling revealed the presence of synaptophysin positive neuroendocrine cells with positive gastrin immunostaining. A conservative approach was adopted, and the patient's symptoms improved on proton pump inhibitors. Zollinger-Ellison syndrome is an important condition, which should be kept in mind in the patient with NF-1 who presents with recurrent peptic ulceration and diarrhea. The emerging association between these 2 conditions is being examined on a cellular and immunohistochemical level.

Topics: Diarrhea; Female; Gastrinoma; Gastrins; Humans; Middle Aged; Neuroendocrine Tumors; Neurofibromatosis 1; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Gastric Mucosa; Gastrins; Humans; Zollinger-Ellison Syndrome

Gastric enterochromaffin-like cell (ECL) tumours can occur in patients with multiple endocrine neoplasia type 1 (MEN1), especially in those affected by Zollinger Ellison syndrome (ZES). Since the prevalence of ECL lesions is not well defined yet, the present study evaluated the presence and extent of ECL lesions in MEN1 patients with and without ZES.. Multiple endocrine neoplasia type 1 patients being part of a regular screening program (2014-2018) underwent gastroduodenoscopies with biopsies of the stomach and determination of serum gastrin and chromogranin A levels. Haematoxylin- and immunostaining with chromogranin A, gastrin and VMAT I and II (vesicular monoamine transporter I and II) of the biopsies were performed.. Thirty-eight MEN1 patients, of whom 16 (42%) were diagnosed and treated earlier for ZES, were analysed. In ten of 16 (62.5%) ZES patients, a locally scattered, mixed image of diffuse, linear and micronodular mild hyperplasia was present. In addition, two of these patients (13%) showed small (max 1.5 mm in size) intramucosal ECL tumours. Neither ECL changes, nor tumours were found in MEN1 patients without ZES (n = 22). In MEN1/ZES patients, the median serum gastrin level was significantly elevated compared to MEN1 patients without ZES (206 pg/ml vs. 30.5 pg/ml, p < .001). A subgroup analysis of the serum gastrin and chromogranin A levels of MEN1/ZES patients with or without ECL hyperplasia did not show significant differences (gastrin level: p = .302, chromogranin A: p = .464).. Enterochromaffin-like cell hyperplasia and gastric carcinoids occur only in MEN1 patients with ZES, but less frequently than reported.

Topics: Carcinoid Tumor; Enterochromaffin-like Cells; Gastrins; Humans; Multiple Endocrine Neoplasia Type 1; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Adult; Bile Duct Neoplasms; Disease-Free Survival; Female; Gastrinoma; Gastrins; Hepatectomy; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Omeprazole; Prognosis; Prospective Studies; Proton Pump Inhibitors; Secretin; Survival Rate; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome is a rare cause of tumoral hypergastrinemia; 1 of 5 patients with this syndrome also has multiple endocrine neoplasia type 1. The diagnosis of this disease is complicated by the widespread use of proton pump inhibitors that can elevate serum gastrin levels, the cornerstone for biochemical diagnosis. Abrupt discontinuation of proton pump inhibitors could lead to adverse outcomes. Clinician awareness of the relationship between Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1 could lead to a safer diagnostic pathway.. We conducted a retrospective review of a cohort of patients with multiple endocrine neoplasia type 1.. There were 287 patients with multiple endocrine neoplasia type 1 (73 with gastrinoma) evaluated between 1997 and 2014. Two patients experienced adverse events after proton pump inhibitor therapy was discontinued to re-measure serum gastrin level during the evaluation of severe peptic ulcer disease. In both cases, the diagnosis of multiple endocrine neoplasia type 1 was made after proton pump therapy was discontinued.. Abrupt discontinuation of proton pump therapy can lead to adverse outcomes in patients with Zollinger-Ellison syndrome. Clinical assessment for features of multiple endocrine neoplasia type 1 (eg, serum calcium levels, personal and family history of hypercalcemia, pituitary or pancreatic tumors) could identify patients with higher risk for a tumoral source of hypergastrinemia where imaging studies can help support the diagnosis without the potential side effects of abrupt discontinuation of proton pump inhibitor therapy.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Proton Pump Inhibitors; Retrospective Studies; Withholding Treatment; Zollinger-Ellison Syndrome

Topics: Barrett Esophagus; Carcinoma, Neuroendocrine; Colonic Polyps; Diagnosis, Differential; Diarrhea; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Recurrence; Vomiting; Weight Loss; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Chromogranin A; Diagnosis, Differential; Fatal Outcome; Female; Gastrins; Humans; Liver; Liver Neoplasms; Middle Aged; Neuroendocrine Tumors; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Gastrinoma; Gastrins; Humans; Laparoscopy; Lymph Node Excision; Male; Young Adult; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma and resultant hypergastrinemia, which leads to recurrent peptic ulcers. Because gastrinoma is the most common pancreatic endocrine tumor seen in multiple endocrine neoplasia type I (MEN 1), the possibility of gastrinoma should be investigated carefully when patients exhibit symptoms associated with hormonal changes. Ureteral stones associated with hyperparathyroidism in the early course of MEN 1 are known to be its most common clinical manifestation; appropriate evaluation and close follow-up of patients with hypercalcemic urolithiasis can lead to an early diagnosis of gastrinoma. We report a patient with ZES associated with MEN 1, and urolithiasis as the presenting entity. A 51-year-old man visited the emergency department with recurrent epigastric pain. He had a history of calcium urinary stone 3 years ago, and 2 years later he had 2 operations for multiple jejunal ulcer perforations; these surgeries were 9 months apart. He was taking intermittent courses of antiulcer medication. Multiple peripancreatic nodular masses, a hepatic metastasis, parathyroid hyperplasia, and a pituitary microadenoma were confirmed by multimodal imaging studies. We diagnosed ZES with MEN 1 and performed sequential surgical excision of the gastrinomas and the parathyroid adenoma. The patient received octreotide injection therapy and close follow-up.

Topics: Gastrinoma; Gastrins; Humans; Immunohistochemistry; Liver; Magnetic Resonance Imaging; Male; Mesenteric Artery, Superior; Middle Aged; Multimodal Imaging; Multiple Endocrine Neoplasia Type 1; Pancreas; Pituitary Gland; Positron-Emission Tomography; Radiopharmaceuticals; Thyroid Gland; Tomography, X-Ray Computed; Ultrasonography; Urolithiasis; Zollinger-Ellison Syndrome

Topics: Adult; Endoscopy, Gastrointestinal; Gastrins; Humans; Male; Proton Pump Inhibitors; Zollinger-Ellison Syndrome

Some patients with Zollinger-Ellison syndrome post curative gastrinoma resection continue to show gastric acid hypersecretion; however, the mechanism is unknown.. The aim of this study was to prospectively study acid secretion following curative gastrinoma resection and analyze factors contributing in patients with Zollinger-Ellison syndrome.. Fifty patients cured post gastrinoma resection were studied with serial assessments of acid secretory status, cure status and ECL-cell status/activity (with serial biopsies, CgA, urinary N-MIAA). Correlative analysis was performed to determine predictive factors.. Hypersecretion occurred in 31 patients (62%) and 14 had extreme-hypersecretion. There was an initial decline (3-6 months) in BAO/MAO, which then remained stable for eight years. Preoperative BAO correlated with the postoperative secretion, but not other clinical, tumoral, laboratory variables, the degree of postoperative acid suppression or type of antisecretory drug needed. Hypersecretors had greater postoperative ECL changes (P=0.005), serum CGA (P=0.009) and 24-h urinary N-MIAA (P=0.0038).. Post curative resection, gastric hypersecretion persists long term (mean 8 years) in 62% of patients and in 28% it is extreme, despite normogastrinemia. No preoperative variable except BAO correlates with postresection hypersecretion. The persistent increased ECL-cell extent post curative resection suggests prolonged hypergastrinemia can lead to changes in ECL-cells that are either irreversible in humans or sustained by unknown mechanisms not involving fasting hypergastrinemia and which can result in hypersecretion, in a proportion of which it can be extreme. Whether similar findings may occur in patients with idiopathic GERD treated for prolonged periods (>10 years) with PPIs, at present, is unknown.

Topics: Enterochromaffin Cells; Female; Follow-Up Studies; Gastric Acid; Gastrinoma; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Pancreatic Neoplasms; Parietal Cells, Gastric; Postoperative Period; Prevalence; Prospective Studies; Zollinger-Ellison Syndrome

A competitive solid-phase assay for the measurement of gastrin in serum using time-resolved fluorescence was developed as an alternative to conventional radioimmunoassay (RIA) technology.. The assay depends on the competitive binding of unlabelled versus Eu-labelled gastrin to specific gastrin antibodies--bound to anti-rabbit IgG immobilized on polystyrene microtitration strips. The bound Eu(3+)-label was dissociated from the bound gastrin and converted to a fluorescent β-diketone chelate which was measured by fluorometry with time-resolution.. Using a sample volume of 50 μl the lower limit of detection was below 10 pmol/L. Dilution of samples showed an excellent linearity. Spiking with gastrin-17 in known concentrations showed a recovery of 103% indicating that there is no bias inherent in the assay. The method correlated fully with the routine in-house radioimmunoassay in the concentration range 10-400 pmol/L (slope = 0.98 with r(2) = 0.98). Thus the reference interval for clinical samples does not require modification when changing from one method to the other.. We have described a convenient and accurate competitive assay for measurement of gastrin in serum based on solid-phase technology using time-resolved fluorometric detection as a realistic alternative to the established state-of-the-art RIA-technology.

Topics: Animals; Fluorometry; Gastrins; Humans; Immune Sera; Immunoassay; Rabbits; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is characterized by hypersecretion of gastric acid, severe peptic ulcerations in the upper small intestine, and diarrhea. It is usually diagnosed by measuring increased levels of gastrin in plasma.. We examined the accuracy of commercial kits to measure gastrin (7 radioimmunoassays and 5 enzyme-linked immunosorbent assays), using plasma from 40 patients suspected or known to have ZES. Each sample was analyzed using the 12 kits and a reference assay that measures bioactive gastrin in plasma, irrespective of size and amino acid derivatization. Known concentrations of peptides with identical sequences to circulating gastrins were also assessed by all assays. Molecular patterns in plasma from patients with ZES were examined by chromatography and monitored by kits that measure false-low or false-high concentrations of gastrin.. Failure to diagnose gastrinomas has serious consequences. Four kits found false-low concentrations of gastrin in 20% to 80% of the patients. Specificity assessment showed that the antibodies used in these kits bound only gastrin-17. Three kits found false-high concentrations of gastrin, because the reagents had increased reactions to sulfated gastrins or to unspecific factors in plasma. Thus, only 5 of 12 kits tested accurately measure plasma concentrations of gastrin.. Seven of 12 tested commercial kits inaccurately measure plasma concentrations of gastrin; these assays used antibodies with inappropriate specificity that were insufficiently validated. Misdiagnosis of gastrinoma based on lack of specificity of assays for gastrin results in ineffective or inappropriate therapy for patients with ZES.

Topics: Adult; Aged; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Reproducibility of Results; Young Adult; Zollinger-Ellison Syndrome

The secretin stimulation test is the principal diagnostic tool to identify Zollinger-Ellison syndrome (ZES). We investigated, by intra-individual comparison, which dose of secretin results in the highest diagnostic efficacy to identify the ZES.. Fifty-seven paired secretin stimulation tests, using both 0.26 microg/kg and 0.78 microg/kg secretin, performed in 13 ZES patients and 12 controls, were analyzed and the findings confirmed in a validation cohort.. A gastrin increase of >100 ng/l was found to be the most sensitive and specific criterion for a positive test. Higher gastrin increases after 0.78 microg/kg compared to 0.26 microg/kg secretin contributed to a slightly more sensitive (82.9 vs. 80.5%) but less specific (68.8 vs. 81.3%) test. A validation cohort, with 98 tests using 0.26 microg/kg secretin in 21 ZES patients and 39 controls, provided similar results. In ZES patients with normal fasting serum gastrin levels (<100 ng/l), there was no diagnostic benefit from the use of a higher secretin dose.. The 0.26 microg/kg secretin stimulation test has the best diagnostic efficacy for the ZES. and IAP.

Topics: Fasting; Female; Gastrins; Humans; Male; Middle Aged; Secretin; Sensitivity and Specificity; Zollinger-Ellison Syndrome

Recent advances in localization techniques, such as the selective arterial secretagogue injection test (SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors (PNET). For patients with sporadic functioning PNET, curative resection surgery has been established by localization with the SASI test using secretin or calcium. For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1 (MEN 1) which are usually multiple and sometimes numerous, resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test. As resection surgery of PNET has increased, several important pathological features of PNET have been revealed. For example, in patients with Zollinger-Ellison syndrome (ZES), duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma, and in patients with MEN 1 and ZES, gastrinomas have been located mostly in the duodenum, and pancreatic gastrinoma has been found to co-exist in 13% of patients. Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation. The most important prognostic factor in patients with PNET is the development of hepatic metastases. The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit. The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.

Topics: Animals; Diagnosis, Differential; Gastrins; Humans; Liver Neoplasms; Male; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

Topics: Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Zollinger-Ellison Syndrome

Most patients with Zollinger-Ellison Syndrome (ZES), even those in whom gastrinoma is found and resected at initial operation, will suffer from persistent or recurrent disease in longterm followup. There is currently no consensus about managing patients with recurrent or persistent ZES. Our unit has historically maintained an aggressive approach toward monitoring and reoperation for patients with sporadic ZES.. We performed a review of a consecutive series of patients evaluated and managed at our institution between 1970 and 2007 for ZES. "Biochemical cure" was defined as normal serum gastrin assays and negative imaging studies. Reoperations were performed for elevations in serum gastrin assays and positive findings on imaging studies.. Fifty-two patients with sporadic ZES were analyzed. Median followup was 14 years. Among patients with sporadic ZES, 37 patients underwent operative management. The most common operations were resection of duodenal gastrinoma (n=8) and total gastrectomy (n=7). Nine patients underwent 15 reoperations for recurrent or persistent disease. "Biochemical cure" was obtained in four patients (44%) undergoing reoperation for ZES. Three of these patients remained without evidence of recurrence at 4, 9, and 12 years after their curative re-resection. Only one of nine patients who underwent reoperation died of metastatic gastrinoma.. Primary and reoperative surgery in patients with sporadic ZES results in a significant rate of "biochemical cure." In selected patients with recurrent or persistent disease, reoperation for resection of gastrinoma is associated with excellent longterm survival and is warranted.

Topics: Adolescent; Adult; Aged; Digestive System Surgical Procedures; Duodenal Neoplasms; Female; Follow-Up Studies; Gastrectomy; Gastrinoma; Gastrins; Hepatectomy; Humans; Male; Middle Aged; Recurrence; Reoperation; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult; Zollinger-Ellison Syndrome

We present a rare case of renal gastrinoma. To the best of our knowledge, only one case of renal gastrinoma has been reported in the literature so far. An African American male was diagnosed with Zollinger Ellison syndrome at the age of 15 years, when he underwent surgery for peritonitis secondary to duodenal ulcer perforation. Further evaluation was deferred and proton pump inhibitors were prescribed. Later evaluation showed a left renal mass. Serum gastrin levels were 4,307 pg/ml. A CAT scan of the abdomen showed 4- x 4-cm heterogeneous solid mass in the interpolar region of the left kidney with central hypodensity. Somatostatin scintigraphy confirmed a receptor-positive mass in the same location. Nephrectomy was done and the tumor was diagnosed on histopathological examination as a gastrinoma. At 6-month follow-up, gastrin levels were 72 pg/ml. After a follow-up of 6 years, the patient has no recurrent symptoms.

Topics: Adolescent; Diagnosis, Differential; Gastrinoma; Gastrins; Humans; Kidney; Kidney Neoplasms; Male; Nephrectomy; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

The purpose of this study is to describe outcomes of MEN-1 patients with recurrence requiring completion pancreatectomy and duodenectomy after initial treatment of pancreatic endocrine neoplasms (PENs) and hypergastrinemia with distal pancreatectomy, enucleation of pancreatic head PENs, and duodenotomy.. After undergoing this initial operation, 8 of 49 patients (16%) have required completion pancreatectomy and duodenectomy for recurrent PENs and hypergastrinemia. Retrospective review was performed.. Median age was 39 years (27-51) at completion pancreatectomy compared to 31 years (20-40) at initial operation. Pathology revealed multiple PENs in 100%, duodenal neoplasms in 63%, and metastatic lymph nodes in 75%. There was no operative mortality and 88% of patients are currently alive. Preoperative gastrin levels were 934 +/- 847 pg/mL while postoperative levels are 93 +/- 79 pg/mL (normal 25-111 pg/mL). Mean Hemoglobin A1C levels are 8.3 +/- 3.3% (normal 3.8%-6.4%). Mean follow-up is 44 +/- 25 months.. This initial operation may provide tumor control and prevent metastases but recurrent PENs are multifocal and progressive. Completion pancreatectomy and duodenectomy is arduous but outcomes are acceptable. Considering the radical nature of this treatment, individual consideration should be given to MEN-1 patients amenable to initial alternative pancreatic resections that preserve pancreatic mass and allow future pancreas-preserving reoperations.

Topics: Adult; Duodenal Neoplasms; Duodenum; Female; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Our aim was to determine whether the glucagon provocative test could be used in place of secretin test in patients with gastrinoma.. Three patients with gastrinoma underwent the following examinations: (1) preoperative intravenous glucagon test to enable a definitive diagnosis, (2) intra-arterial glucagon injection test to localize the tumor, and (3) intraoperative and postoperative intravenous glucagon test to confirm the completeness of the resection.. Serum gastrin levels increased in response to intravenous glucagon in all three patients preoperatively. Computed tomography scans revealed a tumor in the lesser omentum, pancreatic head, and the pancreatic uncinate in cases 1, 2, and 3, respectively. Intra-arterial glucagon test revealed that the feeding artery for the tumor was the left gastric artery in case 1 and the superior mesenteric artery in case 3. Resection of the remnant stomach with tumor, pancreaticoduodenectomy with portal vein resection, and enucleation of the tumor were performed in cases 1, 2, and 3, respectively. Serum gastrin levels did not increase in response to intravenous glucagon intraoperatively and postoperatively in cases 1 and 3. Although intravenous glucagon caused a slight increase in serum gastrin in case 2, no recurrent tumors were evident.. These results indicate that the glucagon provocative test is a suitable alternative to testing with secretin, which is not commercially available in Japan.

Topics: Aged; Female; Gastrins; Gastrointestinal Agents; Glucagon; Humans; Intraoperative Period; Male; Middle Aged; Postoperative Period; Radioimmunoassay; Zollinger-Ellison Syndrome

Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (ZES). These patients can develop proliferative changes of gastric enterochromaffin-like (ECL) cells and gastric carcinoids (ECL-cell tumors). ECL-cell changes have been extensively studied in sporadic ZES patients and can be precursor lesions of gastric carcinoids, but little is known about factors influencing their severity or development of carcinoids in MEN1/ZES patients.. Our objective was to prospectively analyze ECL-cell changes and gastric carcinoids (ECL-cell tumors) in a large series of MEN1/ZES patients to detect risk factors and deduct clinical guidelines.. Fifty-seven consecutive MEN1/ZES patients participated in this prospective study at two tertiary-care research centers.. Assessment of MEN1, gastric hypersecretion, and gastroscopy with multiple biopsies was done according to a fixed protocol and tumor status. ECL-cell changes and alpha-human chorionic gonadotropin staining were assessed in each biopsy and correlated with clinical, laboratory, and MEN1 features.. ECL-cell proliferative changes were universally present, advanced changes in 53% and carcinoids in 23%. Gastric nodules are common and are frequently associated with carcinoids. Patients with high fasting serum gastrin levels, long disease duration, or a strong alpha-human chorionic gonadotropin staining in a biopsy are at higher risk for an advanced ECL-cell lesion and/or gastric carcinoid.. Gastric carcinoids and/or advanced ECL-cell changes are frequent in MEN1/ZES patients, and therefore, regular surveillance gastroscopy with multiple routine biopsies and biopsies of all mucosal lesions are essential. Clinical/laboratory data and biopsy results can be used to identify a subgroup of MEN1/ZES patients with a significantly increased risk for developing gastric carcinoids, allowing development of better surveillance strategies.

Topics: Adolescent; Adult; Aged; Carcinoid Tumor; Enterochromaffin-like Cells; Female; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Prospective Studies; Risk Factors; Stomach Neoplasms; Zollinger-Ellison Syndrome

Zollinger Ellison syndrome (ZES), an ulcerative disease of the upper gastrointestinal tract that involves the production of high levels of gastrin and gastric acid, is a rare, symptomatic, endocrine neoplastic disease.. We report a rare case of gastrinoma that was first diagnosed during pregnancy in which the primary tumor was located in the liver. The ZES was well controlled with Zoton (Lansoprazole) following surgery. The patient had an uneventful pregnancy and delivery without significant complications.. The present case suggests that treatment with Zoton for ZES during pregnancy is safe and effective.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Female; Gastrinoma; Gastrins; Humans; Infant, Newborn; Lansoprazole; Male; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Zollinger-Ellison Syndrome

Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families.. In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach.. Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene.. Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation.. Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.

Topics: Cadherins; Carcinoma, Signet Ring Cell; Gastrins; Humans; Male; Middle Aged; Models, Biological; Multiple Endocrine Neoplasia Type 1; Stomach Neoplasms; Ultrasonography; Zollinger-Ellison Syndrome

Chromogranin has been proposed as a marker for gastrin-dependent enterochromaffin-like cell proliferation.. To examine this question in three populations: acid hypersecretors with gastrinoma (Zollinger-Ellison), or without gastrinoma (non-Zollinger-Ellison), and also in pernicious anaemia with achlorhydria-caused hypergastrinaemia.. We measured serum chromogranin, gastrin, gastric secretion and counted and quantified hyperplasia of enterochromaffin-like cells in gastric biopsies from 38 Zollinger-Ellison and 13 non-Zollinger-Ellison patients being treated with lansoprazole, for 5 years (median) and again 2.5 years later. We also studied 12 patients with pernicious anaemia, half with gastric enterochromaffin-like cell carcinoids.. Serum chromogranin was elevated in patients with gastrinoma, even without any enterochromaffin-like cell proliferation, but not in non-Zollinger-Ellison acid hypersecretors with normal gastrin (P < 0.001). In the hypersecretors chromogranin correlated well with serum gastrin (r = 0.82), but not with enterochromaffin-like cell proliferation. Moreover, chromogranin was normal or near normal (<75 ng/mL) despite very high serum gastrin in five of six patients with pernicious anaemia and enterochromaffin-like cell carcinoids.. Chromogranin is not a reliable marker for enterochromaffin-like cell activity or proliferation up to and including carcinoid; chromogranin originates in the gastrinoma and, like gastrin, is a marker for gastrinoma in acid hypersecretors.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Chromogranin A; Confounding Factors, Epidemiologic; Enterochromaffin Cells; Enterochromaffin-like Cells; Female; Gastrins; Humans; Lansoprazole; Male; Middle Aged; Time Factors; Treatment Outcome; Zollinger-Ellison Syndrome

Topics: Autoimmune Diseases; Diagnosis, Differential; Duodenal Neoplasms; Early Diagnosis; Gastrinoma; Gastrins; Gastritis, Atrophic; Humans; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

The Zollinger-Ellison syndrome is characterized pathophysiologically by a significant hypergastrinemia derived from a gastrin-secreting neuroendocrine tumor with a primary location in the pancreas or duodenum. Chronic hypergastrinemia in turn triggers gastric acid hypersecretion yielding in chronic or recurrent or refractory peptic ulcer disease and/or chronic diarrhea. One half of patients with ZES will have distant metastases in the liver by the time the diagnosis is established and one half of all patients with ZES will experience chronic diarrhea as chief complaint rather than peptic ulcer-related symptoms and signs. Gastrinomas have been reported to either manifest sporadically or to occur in conjunction with the genetic background of the MEN-I syndrome. Diagnosis is based on the patients history which is typically characterized by recurrent episodes of peptic ulcer disease or by severe reflux esophagitis and/or diarrhea or by acid-related symptoms which fail to respond to standard treatment regimens. Upper gastrointestinal tract endoscopy will provide evidence for peptic ulcer disease in anatomical regions located aborally the duodenal bulb within the descending part of the duodenum or even farther distally within the jejunum. Peptic ulcers frequently occur in groups indicating some substantial acid hypersecretion. A gastric pH > 2 is mutually exclusive for ZES. Increased serum gastrin levels confirm the diagnosis biochemically. Gastrin secretion can be determined in the basal state or following stimulation with secretin or calcium. High sensitivity and specificity for the diagnosis of ZES is provided by determining the ratio of basal versus pentagastrin-stimulated gastric acid secretion: The ratio of BAO / MAO > 0.6 is highly specific for gastrinoma. To localize the gastrin-secreting tumor computer-assisted tomography, endoscopic ultrasound, and somatostatin receptor scintigraphy provide useful help but most recently, endoscopic ultrasound with high resolution transducers appear to improve preoperative site localization. If modern imaging techniques fail to elucidate the site of the tumor, intraoperative diaphany may help to detect gastrinomas within the duodenal wall. Definitive treatment will only be achieved by total surgical resection of the gastrin-producing tumor in the pancreas or duodenum including dissection of the regional lymph nodes. Control of symptoms will have to be achieved by administration of highly potent proton pump inhibitors i

Topics: Diagnosis, Differential; Duodenal Neoplasms; Esophagitis, Peptic; Gastric Acidity Determination; Gastrinoma; Gastrins; Humans; Pancreatic Neoplasms; Peptic Ulcer; Proton Pump Inhibitors; Zollinger-Ellison Syndrome

Topics: Cell Transformation, Neoplastic; Enterochromaffin-like Cells; Gastric Acid; Gastrinoma; Gastrins; Gastrointestinal Agents; Humans; Iatrogenic Disease; Proton Pump Inhibitors; Risk Assessment; Stomach Neoplasms; Zollinger-Ellison Syndrome

In 1970-2005 yrs. 65 patients with Zollinger-Ellison syndrome were observed and operated on in the clinic. The decisive meaning in diagnosis owes radioimmunological determination of gastrin level in the blood and its changes while conduction of tests with calcium and secretin. Surgical tactics was determined by localization, number and character of gastrinomas. During the first period of work gastrectomy with complete excision of gastrinproducing tumor constituted the operation of choice. Implementation of intraoperative method of ultrasonography have permitted to excise the benign gastrinoma when her localization was favourable with preservation of stomach. Minimal life span after gastrectomy, performed for nonresectable malignant gastrinoma, have constituted 9 years.

Topics: Adolescent; Adult; Aged; Endoscopy, Gastrointestinal; Female; Gastrectomy; Gastrins; Humans; Male; Middle Aged; Radiography; Treatment Outcome; Ultrasonography; Video-Assisted Surgery; Zollinger-Ellison Syndrome

Type 1 and type 2 diabetes are characterised by a beta cell deficit. Islet hyperplasia has been described in patients with Zollinger-Ellison syndrome secondary to gastrin-producing tumours (gastrinomas), and gastrin therapy has increased beta cell mass in rodents and human islets in vitro. In the present studies we addressed the following questions: (1) In pancreas specimens from gastrinoma cases, is the fractional beta cell area increased? (2) If so, is this restricted to tumour-adjacent islets or also present in tumour-distant islets? (3) Is new beta cell formation (beta cell replication and islet neogenesis) increased and beta cell apoptosis decreased in pancreas specimens from gastrinoma cases?. Pancreas was obtained at surgery from four patients with Zollinger-Ellison syndrome caused by pancreatic gastrinomas and 15 control subjects at autopsy.. Islet fractional beta cell area (p<0.001), islet size (p<0.001) and beta cell replication (Ki67 staining) (p<0.05) were increased in islets adjacent to the tumours, but not in tumour-distant pancreas, compared with control subjects. We did not observe any differences in beta cell apoptosis or in the number of insulin-positive cells in ducts either adjacent to or distant from the tumour.. One or more factors released by human gastrinomas increase beta cell replication in islets immediately adjacent to the tumour, but not in tumour-distant islets. While these findings demonstrate that adult human beta cells can be driven into the cell cycle, they caution against the therapeutic usefulness of gastrin, since islets located >1 cm away from the gastrinomas did not exhibit changes in beta cell turnover, despite markedly elevated systemic gastrin levels sufficient to cause severe gastrointestinal symptoms.

Topics: Body Mass Index; Cell Division; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Gastrinoma; Gastrins; Humans; Insulin-Secreting Cells; Islets of Langerhans; Middle Aged; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

The preoperative localization of gastrinomas often fails despite all modern imaging methods. Therefore, after biochemical confirmation of the diagnosis and exclusion of diffuse metastases, a meticulous surgical exploration including intraoperative ultrasound (IOUS) and duodenal exploration after duodenotomy should be performed. The experienced surgeon will be able to identify more than 90% of the primary tumors. Depending on the localization, excision of the tumor in the duodenal wall or enucleation from the pancreatic head should be performed. If the tumor is localized in the tail of the pancreas, distal pancreatectomy is the treatment of choice. Complete resection of the tumor is the only curative approach for the patients. For MEN-1 gastrinomas a spleen-preserving distal pancreatectomy with enucleation of tumors of the pancreatic head and duodenotomy with excision of duodenal gastrinomas should be performed. If the source of gastrin secretion can be regionalized to the pancreatic head by a preoperative SASI angiography, a pylorus-preserving partial pancreaticoduodenectomy might be the treatment of choice.

Topics: Adult; Aged; Chromosomes, Human, Pair 11; Duodenal Neoplasms; Endosonography; Female; Follow-Up Studies; Gastrinoma; Gastrins; Genes, Dominant; Germ-Line Mutation; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Pancreaticoduodenectomy; Reoperation; Secretin; Stomach Neoplasms; Survival Rate; Zollinger-Ellison Syndrome

Patients with the Zollinger-Ellison syndrome are characterized by islet-cell tumors, striking gastric acid hypersecretion, and peptic ulcer disease. They often experience severe abdominal pain, diarrhea, and gastrointestinal bleeding with potentially life-threatening consequences. It is a rare syndrome caused by non-beta cell islet-cell tumors (gastrinomas) located in or in proximity to the pancreas. These tumors freely secrete gastrin, a peptide hormone that serves as a powerful stimulant of gastric acid secretion. Exuberant secretion of gastrin from the gastrinomas produces severe gastric acid hypersecretion that often leads to impressive peptic ulcer disease and the constellation of symptoms listed above. We describe a patient presenting with clinical manifestations characteristic of the ZES with strikingly elevated gastric acid secretion,multiple ulcers in the first and second portions of the duodenum and diarrhea, but in absence of islet-cell tumor and/or hypergastrinemia.

Topics: Adenoma, Islet Cell; Diarrhea; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Phenotype; Zollinger-Ellison Syndrome

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder with characteristic features of skin and central nervous system involvement. Gastrointestinal involvement is rare, but the risk of malignancy development is considerable. Zollinger-Ellison syndrome is caused by gastrin-secreting tumors called gastrinomas. Correct diagnosis is often difficult, and curative treatment can only be achieved surgically.. A 41-year-old female affected by neurofibromatosis type 1 presented with a history of recurrent epigastric soreness, diarrhea, and relapsing chronic duodenal ulcer. Her serum fasting gastrin level was over 1000 pg/mL. An abdominal CT scan revealed a 3 x 2-cm, well-enhanced mass adjacent to the duodenal loop. She was not associated with multiple endocrine neoplasia type 1. Operative resection was performed and gastrinoma was diagnosed by immunohistochemical staining. The serum gastrin level decreased to 99.1 pg/mL after surgery, and symptoms and endoscopic findings completely resolved without recurrences.. Gastrinoma is difficult to detect even in the general population, and hence symptoms such as recurrent idiopathic peptic ulcer and diarrhea in neurofibromatosis type 1 patients should be accounted for as possibly contributing to Zollinger-Ellison syndrome.

Topics: Adult; Biopsy; Endoscopy; Female; Gastrinoma; Gastrins; Humans; Immunohistochemistry; Neurofibromatosis 1; Proto-Oncogene Proteins c-kit; Tomography, X-Ray Computed; Treatment Outcome; Zollinger-Ellison Syndrome

Topics: Dose-Response Relationship, Drug; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Whereas severe duodenal ulcer is the hallmark of acid hypersecretion in Zollinger-Ellison syndrome (ZE) and similar states, the esophagus also is at high risk. We quantified the incidence of esophagitis and various risk factors that might contribute to it.. Sixty-eight acid hypersecretors (basal acid output >15 mmol/h), 50 patients with ZE, and 18 patients without ZE with normal gastrin levels were studied by gastric analysis, serum gastrin levels, and endoscopy. In 44 of 68 patients, esophageal manometry was performed after the esophagus had healed.. Erosive esophagitis, grade 2 or worse, was found in 65%; an additional 15% had heartburn only, for a total reflux disease incidence of 80%. ZE accounted for 95% of severe esophagitis. Patients with and without esophagitis had the same high overnight fasting gastric residual volume and acidity, as well as basal and peak acid and pepsin outputs. However, patients with esophagitis had a lower median lower esophageal sphincter pressure (LESP) of 15.5 vs. 23 mm Hg in those without symptoms; the critical discriminator threshold was 16 mm Hg. Multivariate analysis further identified frequent vomiting and obesity as positive predictors of esophagitis, whereas Helicobacter pylori was a strong negative predictor (odds ratio, 0.16), possibly related to an elevated LESP in patients infected with H. pylori.. Erosive esophagitis is very common in acid hypersecretors. Identified risk factors that could promote abnormal esophageal exposure to the high acid and pepsin levels in our population of hypersecretors were vomiting, LESP < 16 mm Hg, and obesity, whereas H. pylori appeared to protect the esophagus not by reduced acid, but through an elevated LESP.

Topics: Adult; Age Distribution; Analysis of Variance; Body Weight; Case-Control Studies; Esophagitis; Esophagoscopy; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter pylori; Humans; Incidence; Male; Manometry; Middle Aged; Multivariate Analysis; Probability; Prognosis; Risk Factors; Sampling Studies; Severity of Illness Index; Sex Distribution; Zollinger-Ellison Syndrome

Hypergastrinemia in patients with pernicious anemia is a major regulator contributing to enterochromaffin-cell hyperplasia and, ultimately, to gastric carcinoids.. Between 1990 and 2003, we studied 8 women and 10 men with pernicious anemia and gastric carcinoids; their mean age was 50 years. Serum gastrin levels ranged from 740 to 4,000 pg/mL (mean 1,000 pg/mL). Six patients underwent antrectomy, four total gastrectomy, and eight endoscopic resection or biopsy. During the same period, 22 patients with Zollinger-Ellison tumors and hypergastrinemia (20 men and 2 women, mean age 49 years) had no gastric carcinoids, but 1 of 7 patients with Zollinger-Ellison and multiple endocrine neoplasia (MEN1) tumors had hypergastrinemia and gastric carcinoids.. Mean followup for pernicious anemia patients was 6 years after antrectomy and 1 to 10 years after endoscopic resection or biopsy. Tumor regression was observed in one patient after antrectomy and one patient after biopsy. There were no deaths in this group in spite of lymph node metastasis in two patients. The patient with Zollinger-Ellison and MEN1 syndrome has been followed 3 years after diagnosis and 2 years after total gastrectomy.. Gastric carcinoids are indolent tumors occurring with increasing frequency in patients with pernicious anemia. Antrectomy or biopsy and observation are preferred methods of treatment. Total gastrectomy is reserved for patients with extensive tumor involvement of the gastric wall or for emergency bleeding.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Biopsy; Carcinoid Tumor; Female; Gastrectomy; Gastric Mucosa; Gastrinoma; Gastrins; Gastroscopy; Humans; Hyperplasia; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Retrospective Studies; Stomach Neoplasms; Zollinger-Ellison Syndrome

To analyze the results of a prospective study of 176 patients with Zollinger-Ellison syndrome (ZES) (138 sporadic, 38 MEN1) undergoing 207 operations over a 17-year period.. The existence of lymph node (LN) primary gastrinoma causing ZES is controversial.. Three groups of patients were compared: LN only resected, cured, and no relapse (likely LN primary); same criteria but relapse (unlikely LN primary); and duodenal primary and LN metastases (Duo-LN).. Forty-five (26%) had only LN(s) as the initial tumor found. Twenty-six of the 45 (58%) fit the definition of a likely LN primary because they were apparently cured postresection. At 10.4 +/- 1.2 years, 69% of the 26 patients with likely LN primary tumors have remained cured and have LN primaries. In the 8 of 26 with recurrent ZES, it occurred at 5 +/- 1 years, and 3 had duodenal gastrinoma that had been missed. Ten percent (13/138) of all patients with sporadic ZES and 0% (0/38) with ZES and MEN1 remained cured with only a LN tumor removed. In patients with sporadic gastrinomas no clinical, laboratory, or radiographic localization feature differed among patients with likely LN primary (n = 16) and those with unlikely LN primary (n = 6) or those with Duo-LN (n = 37). In the likely LN primary group, the largest LN was 2.2 +/- 0.2 cm, the number of LNs removed was 1.3 +/- 0.1 (25% > or =1 LN), and 78% were in the gastrinoma triangle, which also did not differ from the other 2 groups. Disease-free survival was similar in the likely LN primary group, patients with Duo-LN, and those with pancreatic primaries.. These results support the conclusion that primary LN gastrinomas occur and are not rare (approximately 10% of sporadic cases). These results suggest that a proportion (25%) of these tumors are either multiple or malignant. Because no clinical, laboratory, or tumoral characteristic distinguishes patients with LN primary tumors, all patients with ZES undergoing surgery should have an extensive exploration to exclude duodenal or pancreatic tumors and routine removal of lymph nodes in the gastrinoma triangle.

Topics: Adult; Diagnostic Techniques, Endocrine; Duodenal Neoplasms; Female; Gastrinoma; Gastrins; Humans; Lymphoma; Male; Middle Aged; Pancreatic Neoplasms; Predictive Value of Tests; Prospective Studies; Zollinger-Ellison Syndrome

The Zollinger-Ellison syndrome consists of severe peptic ulceration, acid hypersecretion, and islet tumors known as gastrinomas. The discovery of gastrinomas in unusual locations such as lymph nodes, bones, ovaries, and the liver poses a diagnostic dilemma as to whether the tumor is primary or metastatic. Here we present a case of a primary gastrinoma within a lymph node.

Topics: Abdominal Pain; Aged; Biopsy; Gastrinoma; Gastrins; Humans; Jejunum; Lymph Nodes; Male; Peptic Ulcer Perforation; Treatment Outcome; Zollinger-Ellison Syndrome

Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter pylori infection, dose and duration of omeprazole treatment may separately, or in combination, influence the proliferation of enterochromaffin-like (ECL) cells and parietal cell changes in gastric mucosa. To assess the effects of these variables comparisons were carried out in patients with the acid related Zollinger-Ellison syndrome (ZES) versus patients with progressive systemic sclerosis (PSS) and gastro-oesophageal reflux disease.. Twenty-five patients with PSS and 16 patients with ZES were included and received continuous omeprazole treatment for a mean of 7.5 and 9 years. The patients were investigated every 6-12 months with endoscopy, biopsies and histology, and plasma gastrin measurements. PSS patients were titrated by 24 h pH-metry to oesophageal pH>4, and all ZES patients were titrated to a basal acid output of zero H+.. Changes towards diffuse and linear ECL cell hyperplasia were observed in 41% of the PSS patients. Micronodular hyperplasia and neoplasia were not seen. In the ZES patients changes towards linear and micronodular hyperplasia were observed in all patients. Two patients developed ECL cell carcinoids; one of these had MEN-1 syndrome. Also parietal cell changes were more pronounced in the ZES group than in the PSS group.. In patients without intrinsic acid hypersecretion and hypergastrinaemia significant proliferation of ECL cells is not an issue irrespective of gastric mucosal inflammation, omeprazole dose, duration of treatment and acid inhibition. The level of gastrin secretion and high plasma gastrin appear to accelerate ECL cell proliferation and parietal cell changes possibly influenced by chronic gastritis and H. pylori infection.

Topics: Achlorhydria; Aged; Aged, 80 and over; Anti-Ulcer Agents; Cell Division; Drug Administration Schedule; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Neurosecretory Systems; Omeprazole; Parietal Cells, Gastric; Scleroderma, Systemic; Zollinger-Ellison Syndrome

Assessment of tumor burden changes is essential for the management of patients with neuroendocrine gastrointestinal (GI) tumors. Chromogranin A (CgA) is a tumor marker for such tumors; however, to the authors' knowledge, there is little information on whether serial assessments can assess changes in tumor burden. In this prospective study of patients with gastrinomas, serial changes in serum CgA levels were compared with changes in levels of the specific tumor marker gastrin to determine whether they reflected changes in tumor burden.. In 72 consecutive patients, the mean CgA and gastrin levels from three determinations were measured on each visit. Changes in markers were correlated with changes in tumor burden determined by imaging. By assessing daily changes, significance changes in CgA and gastrin levels were determined.. During 103 follow-up visits (mean, 9.6 months), an increased tumor size occurred in 25% of patients, no change occurred in 62% of patients, and a decrease occurred in 13% of patients. In patients who had increasing tumor size, CgA levels increased numerically in 77% of patients, gastrin levels increased in 54% of patients, and the increases were significant in 60-80% of patients. In patients who had tumor stabilization, CgA levels in 63% of patients and gastrin levels in 73% of patients did not show a significant change. Decreased tumor size postresection showed a significant decrease in CgA and gastrin levels in all patients. The sensitivity of CgA and gastrin was as follows: sensitivity for detecting an increase, 62% for CgA and 31% for gastrin; sensitivity for detecting no change, 42% for CgA and 75% for gastrin; and sensitivity for detecting a decrease in tumor size, 85% for CgA and 85% for gastrin. The specificity varied from 53% to 99% for CgA and from 49% to 93% for gastrin.. In patients with gastrinomas, serum CgA and gastrin levels varied considerably from day to day, and this must be taken into consideration. Both markers had low sensitivity and specificity for detecting tumor increases and stabilization. For large tumor decreases postresection, both markers had high sensitivity and specificity. The current results suggest that these markers do not have sufficient sensitivity to replace serial imaging studies for detecting important smaller changes in tumor burden in patients with gastrinomas.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chromogranin A; Chromogranins; Female; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies; Sensitivity and Specificity; Zollinger-Ellison Syndrome

Topics: Cell Division; Chronic Disease; Enterochromaffin Cells; Gastric Mucosa; Gastrinoma; Gastrins; Gastritis, Atrophic; Histamine; Humans; Hyperplasia; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Growth factor receptor expression and activation, particularly for epidermal growth factor (EGF) and hepatocyte growth factor (HGF), in many endocrine and nonendocrine tumors is important in determining tumor recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear.. To address this question, we analyzed the extent of EGFR and HGFR expression in gastrinomas from 38 patients with Zollinger-Ellison syndrome and correlated it with clinical and tumor characteristics. EGFR (n = 38) and HGFR (n = 22) mRNA levels were determined by competitive PCR, and immunohistochemistry was performed on a subset.. In each of the gastrinomas studied, detectable levels of EGFR and HGFR mRNA were present. Low levels of EGFR protein expression were detected in 40% of gastrinomas and HGFR protein expression in 90%. EGFR mRNA expression varied by 1050-fold and HGFR by 375-fold. Eighteen percent of gastrinomas overexpressed EGFR mRNA and 14% overexpressed HGFR mRNA, compared with normal pancreas. Maximal EGFR and HGFR mRNA levels were 4- and 1.2-fold increased and correlated with the presence of liver metastases (P = 0.034) and decreased long-term curability (P = 0.027) but not tumor location, size, or tumor functional characteristics.. These above results indicate that EGFR and HGFR mRNA are universally expressed in gastrinomas. Furthermore, each is overexpressed in a minority (15-20%) of the gastrinomas, and the overexpression correlates with aggressive growth and lower curability.

Topics: Adolescent; Adult; DNA Primers; ErbB Receptors; Female; Gastrins; Humans; Immunoenzyme Techniques; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Preoperative Care; Proto-Oncogene Proteins c-met; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Up-Regulation; Zollinger-Ellison Syndrome

Helicobacter pylori infection may increase or decrease acid secretion and may augment proton pump inhibitor efficacy. Pepsin effects have not been reported. In Zollinger-Ellison syndrome (ZE) specifically, H. pylori has been reported to decrease acid.. To examine H. pylori effects on secretion and dose of medication in hypersecretors (basal acid output > 15 mmol/h) undergoing long-term treatment with individually optimized lansoprazole doses.. Sixty-five patients (47 ZE and 18 non-ZE), treated for > 3 months to 10 years, were tested every 6 months with endoscopy, gastric analysis and serum gastrin.. Forty-three per cent were H. pylori-positive. Acid, pepsin and gastrin were not different between H. pylori-positive and H. pylori-negative patients before or during long-term lansoprazole treatment. Initially, H. pylori-positive patients required less lansoprazole than H. pylori-negative patients (68 +/- 6 vs. 96 +/- 8 mg/day), but after 3 years the doses converged (83 vs. 86 mg/day). The disappearance of H. pylori in 15 patients caused no significant changes in acid, pepsin, gastrin or lansoprazole dose in the following 4 years.. H. pylori had no significant initial or long-term physiological or potential clinical effects on acid or pepsin secretion or gastrin in these acid hypersecretors.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Pepsin A; Prospective Studies; Zollinger-Ellison Syndrome

A 55-year-old woman, known with multiple endocrine neoplasia (MEN) type 1, had rectal bleeding and later haematemesis but colonoscopy and gastroduodenoscopy revealed no abnormalities. Due to the normal results for serum gastrin concentration, gastroduodenoscopy and CT scanning of the pancreas, Zollinger-Ellison syndrome was considered to be less likely. Yet the diagnosis could be established on the basis of persistent symptoms and a positive somatostatin receptor scintigraphy. The patient was treated with high doses of a proton pump inhibitor and temporary tube feeding due to weight loss. Follow-up will take place at the endocrinology outpatients' department. Zollinger-Ellison syndrome is a relatively common feature of patients with MEN-1. The diagnosis and localisation of the gastrinoma can be difficult: serum gastrin concentrations can be normal and the sensitivity of CT scanning is low. The primary aim of treating gastrinoma is to control gastric acid hypersecretion by means of high doses of a proton pump inhibitor. The question as to whether surgery is indicated remains controversial.

Topics: Decision Making; Female; Gastrinoma; Gastrins; Hemorrhage; Humans; Middle Aged; Multiple Endocrine Neoplasia Type 1; Proton Pump Inhibitors; Rectal Diseases; Zollinger-Ellison Syndrome

Enterochromaffin-like cell hyperplasia of the gastric body mucosa occurs in hypergastrinaemic conditions such as atrophic body gastritis and Zollinger-Ellison syndrome. However, the time course of change or factors involved are not known.. To compare the rate of change of enterochromaffin-like cell proliferation in patients with atrophic body gastritis and Zollinger-Ellison syndrome.. From a consecutive series of atrophic body gastritis and Zollinger-Ellison syndrome patients, studied at the time of first diagnosis, 10 atrophic body gastritis (4 with pernicious anaemia) and 14 Zollinger-Ellison syndrome (4 with multiple endocrine neoplasia type 1) patients were followed-up for a median time of 48 months.. At entry and during follow-up patients underwent: plasma gastrin determination, endoscopic sampling of body mucosa for qualitative assessment of enterochromaffin-like cell hyperplasia pattern and degree of glandular atrophy, qualitative and morphometric analyses of body mucosa endocrine cells.. At time of diagnosis, enterochromaffin-like cell lesions were more severe in atrophic body gastritis than in Zollinger-Ellison syndrome. During follow-up, no significant variations were observed in gastrin values, enterochromaffin-like cell patterns and grade of body mucosa atrophy in atrophic body gastritis. In contrast, gastrin levels were significantly increased [median 1200 (235-2625) vs 1947 (225-5200) pg/ml; p<0.001)] as was total volume density of enterochromaffin-like cells [median 1.60 (0.53-4.06) vs 3.18 (1.35-21.13)% of mucosal epithelial component; (p<0.005)] in Zollinger-Ellison syndrome. Micronodular hyperplasia of enterochromaffin-like cells, present in only one patient at diagnosis, was observed in 8 Zollinger-Ellison syndrome patients at follow-up.. These data suggest that the progression of enterochromaffin-like cell growth in human gastric mucosa requires an increase of and/or a prolonged exposure to severe hypergastrinaemia.

Topics: Adult; Aged; Disease Progression; Enterochromaffin-like Cells; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Hyperplasia; Immunohistochemistry; Male; Middle Aged; Prospective Studies; Zollinger-Ellison Syndrome

The effect of chronic hypergastrinemia alone on gastric enterochromaffin-like (ECL) cells in humans is largely unknown because in the common chronic hypergastrinemic states (atrophic gastritis, chronic proton pump inhibitor use), it is not possible to separate the effect of hypergastrinemia and other factors, such as gastritis or atrophy. Studies of patients with sporadic Zollinger-Ellison syndrome (ZES) allow this separation.. In 106 patients with ZES, gastric biopsies were taken, and the qualitative ECL cell pattern/grade and the alpha-subunit of human chorionic gonadotropin (alpha-hCG) expression were determined.. In patients with active disease, 99% had ECL hyperplasia and abnormal alpha-hCG staining. Fifty percent had advanced changes in both of these, with 7% having dysplasia and 0% having carcinoids. Advanced ECL cell and alpha-hCG changes were most affected by the level of hypergastrinemia. For ECL cell changes, even mild hypergastrinemia had an effect. Advanced ECL change was also affected by the duration of drug treatment, cure status, and presence of atrophic gastritis, but not by sex or previous vagotomy. The alpha-hCG expression independently predicted dysplasia.. In humans, chronic hypergastrinemia alone causes advanced ECL cell change and abnormal expression of mucosal alpha-hCG. No threshold for this effect was detected, as reported by some, and in contrast to animal studies, sex and vagal tone did not play a major role. The long-term risk of developing gastric carcinoids with chronic hypergastrinemia is low in patients with sporadic gastrinomas (at least 100 times less than in patients with multiple endocrine neoplasia type 1 with ZES) for at least 15-20 years.

Topics: Adolescent; Adult; Aged; Child; Chronic Disease; Enterochromaffin Cells; Female; Gastric Mucosa; Gastrinoma; Gastrins; Glycoprotein Hormones, alpha Subunit; Humans; Hyperplasia; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies; Zollinger-Ellison Syndrome

Helicobacter pylori is said to cause atrophy of the gastric corpus and enterochromaffin-like cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor.. To determine the effect of H. pylori infection on gastritis, enterochromaffin-like cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger-Ellison syndrome) or normal gastrin (non-Zollinger-Ellison syndrome) before and during long-term treatment with lansoprazole.. Lansoprazole was individually titrated to reduce basal acid output to < 5 mmol/h (< 1 mmol/h in post-surgical Zollinger-Ellison syndrome). Gastric corpus biopsies were obtained every 6 months before treatment and up to 8 years later.. H. pylori was present in corpus biopsies in approximately 50%, causing active gastritis which resolved rapidly in 15 subjects after elimination of H. pylori. Patchy mild/moderate corpus atrophy was present at entry in two and at the end in four out of 60 patients, one being H. pylori-positive. Intestinal metaplasia (< 10%) was seen in six isolated biopsies (1% of total). H. pylori did not affect serum gastrin, enterochromaffin-like cell density or hyperplasia. Enterochromaffin-like cell density was twice as high in Zollinger-Ellison syndrome as in non-Zollinger-Ellison syndrome patients (241 vs. 126 cells/mm2, P < 0.001). Enterochromaffin-like cells remained normal in the non-Zollinger-Ellison syndrome hypersecretors regardless of H. pylori status.. Corpus enterochromaffin-like cell increases were related to serum gastrin elevation, but neither H. pylori nor long-term treatment with lansoprazole alone or together had any effect on enterochromaffin-like cell density or hyperplasia. Corpus acute gastritis resulted from H. pylori infection, but did not result in mucosal atrophy despite long-term proton pump inhibitor treatment and promptly resolved with loss of H. pylori.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Enterochromaffin-like Cells; Enzyme Inhibitors; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter pylori; Humans; Hyperplasia; Intestinal Mucosa; Lansoprazole; Male; Metaplasia; Middle Aged; Omeprazole; Zollinger-Ellison Syndrome

Numerous epidemiologic studies suggest a relationship between lung cancer and peptic ulcer disease. Furthermore, various lung cancers synthesize and release a number of peptides such as gastrin and gastrin-releasing peptide that could cause acid hypersecretion; however, Zollinger-Ellison syndrome (ZES), because of a lung tumor, has never been described. We report such a patient for the first time. A 60-year-old man with a non-small cell lung carcinoma (large cell type) presented with diarrhea, heartburn, abdominal pain, and duodenal ulcers. Evaluation showed ZES was present (fasting hypergastrinemia, hyperchlorhydria) and control of all symptoms by omeprazole. No abdominal or cardiac tumor, the other known locations of gastrinomas causing ZES, was found on detailed tumor imaging studies. Resection of the lung tumor resulted in a decrease in gastrin levels to normal values. Plasma radioimmunoassays showed elevated gastrin, chromogranin A and normal levels of gastrin-releasing peptide, and 9 other hormones. The tumor showed similar immunocytochemical results. The characteristics of this case are compared with 100 cases of sporadic abdominal gastrinomas, and the evidence reviewed suggests why ZES should be considered in patients with lung cancer with peptic symptoms.

Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Chromogranin A; Chromogranins; Gastric Acid; Gastrins; Humans; Keratins; Lung Neoplasms; Male; Middle Aged; Synaptophysin; Zollinger-Ellison Syndrome

Eugastrinaemia in Zollinger-Ellison syndrome can be an elusive goal, nearly one third of laparotomies failing to detect the tumour.. A personal series of 13 patients with a mean age of 52 years operated between 1980 and 1996 was reviewed retrospectively. All patients had fasting hypergastrinaemia and recalcitrant ulcer disease with or without diarrhoea.. Computed tomography or selective visceral angiography localised the tumour to the pancreas in 6 of 12 elective patients; the thirteenth presented with a perforated duodenal ulcer. All underwent laparotomy with gastrinoma tissue being completely excised in every case, including the 6 patients with failed pre-operative localisation whose tumours arose from the duodenum (4), pancreas (1) and lymph node (1). Eugastrinaemia was achieved in all but 1 patient and was sustained during a mean follow-up of 5.2 years (SD = 4.2 years). These 12 patients remained clinically free of disease during a mean clinical follow-up of 7.5 years (SD = 5.0 years; range 2-19 years). There were no postoperative deaths, but 3 died from recurrent tumour at 3-7 years.. Since normalisation of serum gastrin was achieved in 12 of 13 patients, laparotomy may well be worthwhile even if the gastrinoma cannot be localised pre-opera- tively.

Topics: Adult; Aged; Angiography, Digital Subtraction; Fasting; Female; Gastrectomy; Gastrins; Gastroscopy; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatectomy; Pancreaticoduodenectomy; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Zollinger-Ellison Syndrome

To assess the value of the initial fasting serum gastrin (FSG) at presentation in patients with Zollinger-Ellison Syndrome (ZES) in predicting primary tumor characteristics and survival.. A total of 239 patients were treated for ZES between December 1981 and September 1998, with a mean follow-up of 9.1 +/- 0.6 years. At initial evaluation, 86 patients (36%) had mild (0 to 499 pg/mL), 61 (25.5%) had moderate (500 to 1,000 pg/mL), and 92 (38.5%) had severe (> 1,000 pg/mL) elevations in FSG. Primary tumor location and size, presence of lymph node or hepatic metastases, and survival were analyzed based on the level of initial FSG.. In patients with sporadic ZES, but not in those with multiple endocrine neoplasia type 1 (MEN-1) and ZES, there was a significant relationship between the level of initial FSG and tumor size and location of primary tumor, frequency of lymph node and liver metastases, and survival. The median 5- and 10-year survival decreased with increasing initial FSG (P <.001) in patients with sporadic ZES; MEN-1 patients lived longer than sporadic ZES patients (P =.012), and survival in this group was not associated with the level of initial FSG. Multivariate analysis showed that factors independently associated with death from disease in patients with sporadic ZES were liver metastases (P =.0001), a pancreatic site (P =.0027), and primary tumor size (P =.011) but not initial FSG (P >.30).. The severity of FSG at presentation is associated with size and site of tumor and the presence of hepatic metastases, factors that are significant independent predictors of outcome. The level of FSG at presentation may be useful in planning the nature and extent of the initial evaluation and management in patients with sporadic ZES.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Child; Female; Gastrins; Humans; Incidence; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Survival Analysis; Survival Rate; United States; Zollinger-Ellison Syndrome

Topics: Abdominal Pain; Adrenal Gland Neoplasms; Diabetes Mellitus, Type 1; Esophageal Stenosis; Gastrins; Humans; Hypercalcemia; Male; Middle Aged; Zollinger-Ellison Syndrome

To ascertain the frequency and the clinico-functional correlations of intramucosal cysts in the gastric body of patients with the Zollinger-Ellison syndrome (ZES) and to clarify the relevant mechanism of development, a total of 106 consecutive ZES patients (58 M, 48 F; mean age: 53 yrs, range 19-93 yrs) were investigated with a mean of 7.2 biopsy specimens of the body mucosa per patient proved to be suitable for the study. Biopsies of endoscopically detectable polypoid lesions were not considered. Cystic changes were evaluated with respect to their severity by assessing the cyst grade (0, absent, 1; <30%, 2; 30-60%; 3 >60% of the mucosal area of the biopsy specimen of individual patients showing the most pronounced finding, respectively) and to their intragastric distribution by assessing the ratio of biopsy specimens showing cystic changes over the total number of biopsies examined in each patient. Intramucosal cysts were found in biopsies of non-polypoid gastric body mucosa in 71.7% of 106 patients with Zollinger-Ellison syndrome (ZES) and showed grade 2 and 3 severity in 22 and 8 cases, respectively. The severity of cystic changes correlated with the gastrin levels (p = 0.0005) and was more advanced in patients with active than in those with cured disease (p = 0.037). In the former group, furthermore, advanced cystic changes correlated with age (p = 0.03), male gender (p = 0.014), years of disease from onset (p < 0.02), years of omeprazole treatment (p = 0.033), basal acid output (p < 0.02), severity of ECL cell proliferative changes (p = 0.028), and absence of previous gastrinoma resection (p = 0.039) whereas they did not correlate with MEN-1 status, gastritis, maximal acid output, total duration of any antisecretory drug treatment, daily doses of omeprazole (> 20 mg vs 20 mg), years from surgery, duodenal localization of gastrinoma(s), presence of gastric carcinoid tumor(s) and of liver metastases. In groups of patients subdivided according to three levels of serum gastrin, the duration of omeprazole treatment was not related to the severity of cystic changes. It is concluded that intramucosal cysts in non polypoid gastric body mucosa of ZES patients are by far more common than the already reported fundic gland polyps, to which they likely give raise. Circulating levels of gastrin have an important independent role in their development.

Topics: Adult; Aged; Aged, 80 and over; Aging; Biopsy; Cell Division; Cysts; Enterochromaffin Cells; Female; Gastric Acid; Gastric Mucosa; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Omeprazole; Sex Characteristics; Stomach; Stomach Neoplasms; Zollinger-Ellison Syndrome

We report a case of pseudo-Zollinger-Ellison syndrome in a 17-year-old man presenting with gastrin levels exceeding 2000 pmol/l and BAO 24 mEq/hr. Histologically, apart from hypertrophic gastritis with the thickening of mucosal folds and diffuse G-cell hyperplasia, gastric mucosa was found to contain foci of pancreatic metaplasia.

Topics: Adolescent; Gastric Acidity Determination; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Gastritis; Humans; Hyperplasia; Male; Metaplasia; Pancreas; Stomach; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrectomy; Gastrins; Gastrointestinal Agents; Humans; Zollinger-Ellison Syndrome

Topics: Gastric Fundus; Gastrins; Humans; Polyps; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Adult; Antineoplastic Agents; Carcinoid Tumor; Female; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Octreotide; Peptides, Cyclic; Somatostatin; Stomach Neoplasms; Zollinger-Ellison Syndrome

We describe herein the case of a 54-year-old Japanese woman in whom an inveterate peptic ulcer developed in association with pseudo-Zollinger-Ellison Syndrome (pseudo-ZES). The patient presented with weight loss and abdominal distension caused by antral and duodenal stenosis due to an inveterate peptic ulcer. Her serum gastrin level was very high; however, no evidence of a gastrinoma or carcinoid tumor was detected by preoperative examinations or surgery. A total gastrectomy and double-tract reconstruction was performed, and pathological examination revealed a gastric ulcer (UL-IV) with no histopathological evidence of a neoplasm. Immunohistochemical staining showed an obvious increase in the number of endocrine cells that were positive for chromogranin A, and marked G-cell hyperplasia was observed in the antral mucosa. Furthermore, the number of enterochromaffin-like cells was remarkably high. From the results of the immunohistochemical examination, the patient was diagnosed as having hypergastrinemia due to antral G-cell hyperplasia. Postoperatively, the patient's serum gastrin level fell rapidly to within the normal range, her nutritional status improved, and her weight increased by about 10 kg within 1 year.

Topics: Diagnosis, Differential; Female; Gastrectomy; Gastrin-Secreting Cells; Gastrinoma; Gastrins; Humans; Hyperplasia; Immunohistochemistry; Middle Aged; Peptic Ulcer; Pyloric Antrum; Treatment Outcome; Zollinger-Ellison Syndrome

We present a 57-year-old man with Zollinger-Ellison syndrome who had undergone total gastrectomy 12 years previously. At that time, a cystic mass in the left lobe of the liver was palpated but was not removed. The patient currently had high serum gastrin levels. Abdominal ultrasound, CT and MR images showed a well defined liver mass with solid and cystic components. The lesion was resected and a primary hepatic carcinoid tumour was diagnosed. Post-operatively, serum gastrin levels were normal. A primary liver carcinoid may appear as multicystic liver mass with solid components. Careful exclusion of a primary tumour elsewhere is required to establish the diagnosis of this rare entity.

Topics: Carcinoid Tumor; Gastrins; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Zollinger-Ellison Syndrome

Intravenously administered secretin stimulates pancreatic polypeptide (PP) release in patients with endocrine enteropancreatic tumors, but data in patients with nontumorous disorders are controversial. Therefore, we aimed to evaluate the plasma PP pattern after secretin administration in healthy subjects and in patients with gastroduodenal diseases investigated for recurrent ulcer disease and/or hypergastrinemia.. Synthetic secretin was given as an intravenous bolus (2U/kg) in ten patients with Zollinger Ellison syndrome, ten with duodenal ulcer, ten with atropic gastritis and ten healthy volunteers. Blood samples were taken before and at regular intervals for 30min after secretin injection. Plasma PP and gastrin levels were measured by radioimmunoassay.. Secretin promptly and significantly (P<0.01) increased PP plasma levels in all groups of subjects without any differences in peak values. There were no significant correlations between PP and gastrin plasma levels.. Secretin at pharmacological doses is a powerful stimulus for PP release.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastrins; Gastritis, Atrophic; Humans; Kinetics; Male; Middle Aged; Pancreatic Polypeptide; Secretin; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Echinococcosis, Hepatic; Follow-Up Studies; Gastrinoma; Gastrins; Hepatectomy; Humans; Liver Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Topics: Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Hypoglycemia; Neoplasm Proteins; Thyrotropin; Zollinger-Ellison Syndrome

This study evaluates whether a new analytic principle, processing-independent analysis (PIA), offers better specificity and sensitivity than the conventional gastrin radioimmunoassay in the diagnosis of gastrinomas.. Plasma concentrations of alpha-amidated gastrins and the total progastrin product were measured with radioimmunoassay and with PIA, respectively, in 512 samples taken for gastrin measurement and in a selected group of gastrinoma patients (n=10).. Among the 512 patients were 9 with gastrinomas. In plasma from these patients the median degree of amidation (ratio of alpha-amidated gastrins to total progastrin product) was 75% (range, 25-98%), whereas in the other groups the medians varied from 41% to 86%. In the second group of gastrinoma patients all had a degree of amidation of less than 50%.. In screening for gastrinomas PIA offered no diagnostic advantages in comparison with conventional gastrin radioimmunoassay. However, in selected patients who in spite of normal or slightly increased concentrations of amidated gastrins were still suspected of having gastrinoma, additional measurement of the total progastrin product showed incomplete processing of progastrin and thus proved helpful in establishing the diagnosis.

Topics: Anti-Ulcer Agents; Case-Control Studies; Female; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Protein Precursors; Radioimmunoassay; Sensitivity and Specificity; Zollinger-Ellison Syndrome

Despite recent advances in imaging techniques for endocrine tumors of the duodenum and the pancreas, preoperative localization of gastrinomas is inconsistent. Successful surgical management of patients with Zollinger-Ellison syndrome (ZES) and removal of all gastrin-secreting tumors remains a difficult task. The aim of the study was to evaluate the predictive value of intraoperative gastrin measurements for successful surgical treatment in patients with gastrinomas. Intraoperative gastrin measurements were performed in 20 patients with ZES who underwent resection of gastrin-secreting tumors. Gastrin was measured with a radioimmunologic assay in blood samples obtained from a peripheral vein and from the portal vein at the beginning of the operation (T0) and 20 minutes after removal of the lesion(s) (T1). In 16 patients gastrin was also measured 4 minutes after injection of secretin 3 U/kg (T2). Thirteen patients (65%) were cured by surgery. In two of them, peripheral and portal gastrin levels were normal at T0, precluding any further interpretation of the test. Completeness of surgery was confirmed by normalization of gastrin levels at T1 or the absence of stimulation at T2 (or both) in 10 patients. In only one case did the gastrin levels remain elevated at T1 despite a favorable outcome after surgery. In each of the seven patients (35%) who had persisting disease at 1 year, failure of the surgical procedure was predicted by persistence of high levels of gastrin at T1. In patients with hypergastrinemia, the positive predictive value of intraoperative gastrin measurement for completeness of surgery and the specificity were 100%. The negative predictive value was 88% and the sensitivity 91%. The overall accuracy of the test was 94%. In patients with ZES the normalization of systemic hypergastrinemia during surgery affirms the successful removal of all gastrin-secreting tumors. We conclude that intraoperative gastrin measurement is a valuable addendum for optimizing the surgical management of gastrinoma.

Topics: Gastrins; Humans; Monitoring, Intraoperative; Zollinger-Ellison Syndrome

This report concerns a case of a Cushing's syndrome 10 years after first diagnosis of a Zollinger-Ellison syndrome within the same patient. In a 69-year-old female patient symptoms of hypergastrinaemia have been successfully treated with a proton pump inhibitor. Cushing's syndrome was the result of ectopic adrenocorticotropic hormone production by a large cystic gastrin-producing tumour of the pancreatic tail. After resection by subtotal pancreatectomy serum adrenocorticotropic hormone, cortisol, gastrin levels and secretin infusion test returned to normal. In contrast to all other previously published cases of ectopic adrenocorticotropic hormone syndrome associated with Zollinger-Ellison syndrome, this tumour had not metastasized into the liver and did not show local invasive growth.

Topics: Adrenocorticotropic Hormone; Aged; Anti-Ulcer Agents; Cushing Syndrome; Female; Gastrinoma; Gastrins; Humans; Hydrocortisone; Immunohistochemistry; Omeprazole; Pancreatectomy; Pancreatic Neoplasms; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Animals; Dog Diseases; Dogs; Duodenum; Gastric Mucosa; Gastrinoma; Gastrins; Intestinal Mucosa; Male; Necrosis; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Female; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Zollinger-Ellison Syndrome

Topics: Aged; Contrast Media; Duodenal Neoplasms; Gastrinoma; Gastrins; Humans; Image Processing, Computer-Assisted; Intubation, Gastrointestinal; Male; Pyloric Antrum; Receptors, Somatostatin; Stomach Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Topics: Adult; Carcinoid Tumor; Duodenal Neoplasms; Gastrins; Humans; Male; Somatostatin; Tomography, Emission-Computed, Single-Photon; Zollinger-Ellison Syndrome

The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development.. To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics.. Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p < 0.001).. Immunohistochemistry was performed on 3 microns sections of rectal biopsy specimens incubated with 5'-bromodeoxyuridine.. The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (phi h value) was significantly higher in patients with CAG or ZES compared with controls (p < 0.01 in both patient groups versus controls).. Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.

Topics: Adult; Aged; Autoimmune Diseases; Cell Division; Chronic Disease; Colonic Neoplasms; Female; Gastrins; Gastritis; Humans; Immunohistochemistry; Male; Middle Aged; Rectum; Risk Factors; Zollinger-Ellison Syndrome

To evaluate localization of hepatic metastases with the intraarterial secretin injection test in Zollinger-Ellison syndrome (ZES).. Results in 74 patients with ZES (aged 15-70 years) were retrospectively studied. All patients had undergone computed tomography (CT), magnetic resonance (MR) imaging, ultrasound, abdominal angiography, and an intraarterial secretin test, in which venous blood is sampled periodically after injection of secretin.. Twenty-two patients had liver metastases. An increase in venous gastrin concentration of at least 25% at 20 seconds or 50% at 30 seconds after injection indicated a positive result. Results were positive in 41% of patients with and 2% without liver metastases (P < .0001). Sensitivity of the intraarterial secretin test was 41%; of CT and ultrasound, 64%; and of MR imaging and angiography, 77%. Intraarterial secretin test results assisted in clinical management in 22% of patients.. With the criteria developed, the intraarterial secretin test had high specificity but low sensitivity. It should be used when imaging results are unclear.

Topics: Adolescent; Adult; Aged; Angiography; Female; Gastrinoma; Gastrins; Hepatic Artery; Hepatic Veins; Humans; Injections, Intra-Arterial; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Pancreatic Neoplasms; Retrospective Studies; Secretin; Sensitivity and Specificity; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

Whereas considerable experimental evidence suggests chronic hypergastrinemia can increase the occurrence of colonic neoplasia, the risks in man remain unclear. Zollinger-Ellison syndrome (ZES) is associated with marked plasma elevation of all forms of gastrin and, because of its prolonged course, has been shown to be an excellent model disease to study the effects of chronic hypergastrinemia in man. To determine whether profound chronic hypergastrinemia affects the occurrence of colonic dysplasia and neoplasia, 97 consecutive patients with ZES were studied. All patients underwent colonoscopic examination to the cecum, and the location, size, and type of polyps/tumors were determined. The patients had a mean fasting gastrin level 31 times above normal and a mean disease duration of 10 years; 17/97 (18%) had adenomatous polyps, 67/97 (69%) no adenomatous polyps, and 2/97 (2%) had colonoscopy and/or autopsy studies fo asymptomatic controls. Stratification by age or gender, presence of MEN-I, tumor extent, and duration of degree of hypergastrinemia did not increase prevalence. This study shows that despite prolonged, profound hypergastrinemia, no increased rate of colonic neoplasia (polyps or cancer) was noted. These data suggest that the development of hypergastrinemia secondary to continuous use of H+,K+-ATPase inhibitors for as long as 10 years is unlikely to cause an increased risk of developing colonic neoplasia in man.

Topics: Adenocarcinoma; Adenomatous Polyps; Age Distribution; Chronic Disease; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Fasting; Female; Gastrins; Humans; Incidence; Male; Middle Aged; Risk Factors; Sex Distribution; Zollinger-Ellison Syndrome

Gastrinoma is a kind of neuroendocrine tumor very rare in children. It can be described as solitary and has been reported in the liver and in the kidney; or as part of MEN type I (tumors of parathyroids, pancreatic islets and pituitary). We report here, a solitary and huge pancreatic gastrinoma in a young girl with a Zollinger-Ellison (Z-E) syndrome, whose diagnosis was delayed by misunderstanding of the symptoms.

Topics: Adolescent; Diagnosis, Differential; Female; Gastrinoma; Gastrins; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

A patient with long-standing Zollinger-Ellison syndrome, treated for 14 years with antisecretory agents, underwent computed tomography and upper gastrointestinal examination because of upper gastrointestinal bleeding. Radiologic and pathologic examinations showed multiple nodular masses arising from the wall of the stomach that were determined to be mucosal carcinoid tumors. A gastrin-producing islet cell tumor of the pancreatic head was also present. Gastric carcinoid tumors occurred as a consequence of chronic hypergastrinemia.

Topics: Carcinoid Tumor; Gastrins; Humans; Male; Middle Aged; Stomach Neoplasms; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

During a period of 13.5 years 17 patients with a gastrinoma and an associated Zollinger-Ellison syndrome were treated. In three patients (18%) the gastrinoma was part of a multiple endocrine neoplasia type I (MEN I). The median interval from the initial symptoms to the definite diagnosis was 5.0 years. During this interval seven patients (41%) underwent gastric surgery up to four times. The preoperative imaging studies localized the primary tumor in only seven patients (41%). In five of six diagnostic laparotomies the primary site of the tumor was identified and proved by pathologic work-up. The surgical procedures (n = 13) included five resections of the pancreas (3 x pancreatic head, 2 x left pancreatic resection), two duodenal resections, three enucleations of the tumor and three palliative operations (hospital mortality: 0%). Following laparotomy the gastrinoma could be histologically proved in eleven of 17 patients (6 x pancreas, 4 x duodenum, 1 x in the hepatoduodenal ligament). The rate of metastatic spread as characteristic feature of malignancy was 59%. After complete resection of the primary tumor (n = 8) none of these patients died because of the gastrinoma during the follow-up (median: 7.3 years). In the remaining patients three deaths were caused by the metastatic spread of the gastrinoma. Considering the high rate of preceding operations, the high malignancy rate and the excellent prognosis after RO-resection the diagnostic interval in patients with ZES is too long. Despite the modern radiographic imaging the exploratory laparotomy is of high value in patients with ZES.

Topics: Adult; Aged; Duodenal Neoplasms; Duodenum; Female; Follow-Up Studies; Gastrectomy; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreas; Pancreatic Neoplasms; Postoperative Complications; Reoperation; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Female; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

The role of surgical resection of gastrinoma in multiple endocrine neoplasia type 1 (MEN 1) is controversial because of low biochemical cure rates, but with adequate duodenal exploration higher cure rates may be possible.. We have prospectively evaluated this proposal in ten consecutive patients with MEN 1 and Zollinger-Ellison syndrome who underwent surgical exploration for gastrinoma resection including a detailed evaluation of the duodenum by palpation, intraoperative endoscopy with transillumination, and duodenotomy.. Duodenal tumors were present in seven patients. Six of seven patients had metastatic deposits in lymph nodes, and two of seven had synchronous pancreatic tumors. Three patients had a single duodenal tumor, one patient had two tumors, and three patients had more than 20 duodenal tumors. Positive gastrin staining by use of immunohistochemistry was seen in all duodenal tumors. None of these seven patients were biochemically cured. Of three patients with negative duodenal explorations, two had single pancreatic tumors removed and one had only lymph node gastrinoma. No patients were biochemically cured.. Not all patients with MEN 1 and Zollinger-Ellison syndrome have duodenal gastrinomas. In the 70% of patients with duodenal tumors, even extensive duodenal exploration with removal of positive lymph nodes does not result in cures because 86% of tumors had metastasized to lymph nodes and 43% of patients had large numbers of tumors.

Topics: Adult; Duodenal Neoplasms; Female; Gastrinoma; Gastrins; Humans; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Prospective Studies; Zollinger-Ellison Syndrome

Persistent severe vomiting in pregnancy may be caused by underlying disease and should be investigated. A patient with intractable vomiting associated with abdominal pain and dental enamel erosion in two pregnancies had a gastrinoma. Symptoms were successfully controlled with omeprazole in a third pregnancy. All three babies were healthy.

Topics: Adult; Anti-Ulcer Agents; Female; Gastric Acid; Gastrins; Humans; Nausea; Omeprazole; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Tomography, X-Ray Computed; Vomiting; Zollinger-Ellison Syndrome

Topics: Cell Division; Colorectal Neoplasms; Gastrins; Humans; Intestinal Mucosa; Rectum; Risk Factors; Zollinger-Ellison Syndrome

The introduction of sensitive radioimmunoassays for gastrin has led to the earlier and more accurate diagnosis of gastrinomas and, as methods for tumour localization both pre- and intraoperatively have improved, the emphasis of surgery has changed from control of gastric acid secretion to tumour removal. We present three cases of sporadic gastrinoma who underwent exploratory laparotomy. In two cases, gastrinomas were discovered and excised resulting in cure for one patient. The third case underwent a negative laparotomy. The changes in serum gastrin levels taken during and immediately after surgery were related to the success or otherwise of tumour removal in each of the three cases. As in parathyroid surgery, with the development of rapid radioimmunoassays, the intraoperative measurement of declining serum gastrin levels will help in the early definition of surgical success supplementing frozen section and clinical judgement and improving patient management.

Topics: Adult; Duodenal Neoplasms; Female; Gastrins; Humans; Intraoperative Care; Laparotomy; Middle Aged; Preoperative Care; Radioimmunoassay; Stomach Neoplasms; Zollinger-Ellison Syndrome

The present report describes two patients with fasting hypergastrinemia, gastric acid hypersecretion, and Helicobacter pylori gastritis. Provocative testing for Zollinger-Ellison syndrome was negative and imaging studies did not demonstrate an intra-abdominal mass. Following eradication of the Helicobacter pylori infection, the fasting hypergastrinemia resolved in both patients and in one patient the gastric acid hypersecretion also resolved. The implications of this case on the differential diagnosis of Zollinger-Ellison syndrome are discussed.

Topics: Adolescent; Adult; Diagnosis, Differential; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Zollinger-Ellison Syndrome

Manifestations of esophageal disease are present in up to 60% of patients with Zollinger-Ellison syndrome (ZES), although esophageal function has been studied in only a few patients and the prevalence of Barrett's mucosa is unknown in these patients. It is unclear whether the high prevalence of esophageal disease is related to gastric acid hypersecretion alone or to abnormalities of esophageal motility or lower esophageal sphincter (LES) function in addition. To address these issues in the present study esophageal function was evaluated prospectively in 92 consecutive patients with ZES (66 with active disease, 26 disease-free after curative resection) seen during a 1-year period after controlling acid hypersecretion. In the patients with active disease the mean basal acid output (BAO) was 33 +/- 3.0 mEq/h, the maximal acid output (MAO) was 56 +/- 4.0 mEg/h, fasting serum gastrin was 8,736 +/- 4,813 pg/ml and duration of disease prior to study was 12.5 +/- 2.0 years. At the time of manometry, gastric acid secretion was controlled in all patients and no patient had evidence of gastroesophageal reflux disease at upper gastrointestinal endoscopy. Esophageal manometry revealed normal motility in 85% of patients. Eleven percent had low LES pressures, and only 1% of patients had an elevated LES pressure. The frequency of Barrett's mucosa (3%) was similar to that found in the general population but much less than that reported in patients with idiopathic GERD. No correlation was noted between LES pressures or manometric abnormalities and the fasting serum gastrin, BAO, MAO or the presence or absence of multiple endocrine neoplasia type I or previous vagotomy. Esophageal manometric results and LES pressure were similar in disease-free patients and those with active ZES. In conclusion, these results suggest that hypergastrinemia or other disease-specific abnormalities are not contributing to the high incidence of esophageal disease in patients with ZES because esophageal function in patients with ZES is similar to normals. Specifically, motility disorders in patients with ZES occur in similar frequency to normals, and LES pressure is normal in most patients. Despite the high levels of acid secretion and prominence of symptoms, the occurrence of Barrett's mucosa was uncommon (3%) raising the possibility of additional protective mechanisms in patients with ZES.

Topics: Adult; Aged; Barrett Esophagus; Biopsy; Endoscopy, Digestive System; Female; Follow-Up Studies; Gastric Acid; Gastrins; Humans; Male; Manometry; Middle Aged; Prospective Studies; Zollinger-Ellison Syndrome

Radioimmunoassays are sensitive and specific methods for measurement of the concentrations of regulatory peptides. However, aspects of physiological, pathophysiological and pharmacological research require knowledge about the biological activity which does not necessarily vary concomitantly with immunological activity. The present work describes a simplified bioassay for gastrin based on the gastric histamine releasing properties of this peptide, using an isolated vascularly perfused rat stomach preparation with a crystalline perfusate and a specific radioimmunoassay for histamine. The establishment of a dose-response curve is described, as well as the utilization of the bioassay on sera from patients with hypergastrinaemia. The method is sensitive for gastrin in the low (4 pmol L-1) picomolar range.

Topics: Anemia, Pernicious; Animals; Biological Assay; Gastric Mucosa; Gastrins; Gastritis; Histamine Release; Humans; Male; Perfusion; Rats; Rats, Wistar; Reproducibility of Results; Sensitivity and Specificity; Stomach; Zollinger-Ellison Syndrome

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Blood Chemical Analysis; Combined Modality Therapy; Duodenal Neoplasms; Female; Gastric Acid; Gastric Mucosa; Gastrinoma; Gastrins; Hepatic Artery; Humans; Interferons; Lansoprazole; Male; Middle Aged; Multiple Endocrine Neoplasia; Omeprazole; Pancreatic Neoplasms; Peptic Ulcer; Splenic Artery; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Omeprazole; Zollinger-Ellison Syndrome

Many patients with acid-peptic disease have idiopathic gastric acid hypersecretion defined as a basal acid output > 10.0 meq/hr; however, a significant proportion have basal acid outputs > 15.0 meq/hr, which is within the range found in Zollinger-Ellison syndrome. Although idiopathic gastric acid hypersecretion is more common than Zollinger-Ellison syndrome, it is important that these two disorders be differentiated because of differences in treatment and natural history. In the present study, we compared 124 patients with idiopathic gastric acid hypersecretion and 137 patients with Zollinger-Ellison syndrome. There were no significant differences with regard to age at diagnosis, history of upper gastrointestinal hemorrhage, nausea, vomiting, and family history of duodenal ulcer and other acid-peptic disease. However, significant differences were observed between patients with idiopathic gastric acid hypersecretion and patients with Zollinger-Ellison syndrome with regard to percentage of males: 77% compared to 64% (P = 0.008), mean serum gastrin: 60 pg/ml compared to 3679 pg/ml (normal < 100 pg/ml) (P < 0.001), mean basal acid output: 15.4 meq/hr compared to 47.0 meq/hr (P < 0.001), mean age at onset of symptoms: 33 years compared to 41 years (P < 0.001), mean duration of symptoms before diagnosis: 11 years compared to five years (P < 0.001), percentage with abdominal pain: 67% compared to 82% (P = 0.00004), percentage with diarrhea: 12% compared to 75% (P < 0.000001), percentage with pyrosis: 58% compared to 40% (P = 0.003), percentage with duodenal ulcer: 53% compared to 74% (P < 0.000001), and percentage with esophagitis: 31% compared to 42% (P = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Age of Onset; Aged; Aged, 80 and over; Diagnosis, Differential; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

We measured basal and pentagastrin-stimulated acid secretion, as well as basal and meal-stimulated plasma gastrin concentration to determine, in 67 patients affected by resistant duodenal ulcer, whether their condition could be related to gastric acid secretion and/or gastrin-related syndromes. We then compared them to 46 duodenal ulcer control patients. The outpatients were investigated consecutively. The resistant duodenal ulcer patients differed from the controls only in their higher complication rates (bleeding or perforation, P < 0.05). We identified five patients in the resistant duodenal ulcer group with Zollinger-Ellison syndrome and 12 with antral G cell hyperfunction, whereas in the control group only one patient was affected by antral G cell hyperfunction. IgG anti-Helicobacter pylori antibodies were positive for the presence of infection in 7 of the hypergastrinaemic patients. When Zollinger-Ellison syndrome or antral G cell hyperfunction were excluded, no differences could be found in gastric acid secretion, or basal and meal-stimulated plasma gastrin levels, between the resistant and control duodenal ulcer patients, except for basal acid hypersecretion (resistant duodenal ulcer 16% vs duodenal ulcer 2% P = 0.0144). In the presence of duodenal ulcer disease resistant to H2-blockers, it is mandatory to measure basal plasma gastrin concentration since it was possible to diagnose the gastrin-related syndromes, Zollinger-Ellison syndrome and antral G cell hyperfunction, in 26% of this group of patients.

Topics: Adult; Aged; Antibodies, Bacterial; Duodenal Ulcer; Enzyme-Linked Immunosorbent Assay; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pyloric Antrum; Zollinger-Ellison Syndrome

In the rat, hypergastrinaemia induced by drug treatment with omeprazole or potent H2-receptor antagonists leads to the development of gastric enterochromaffin-like cell carcinoids. In man, gastric carcinoids induced by hypergastrinaemia have been described only in patients with chronic atrophic gastritis type A and in patients with the multiple endocrine neoplasia syndrome type 1. This patient with Zollinger-Ellison syndrome without gastric mucosal atrophy and without evidence of the multiple endocrine neoplasia syndrome developed an argyrophil gastric carcinoid tumour. This observation indicates that hypergastrinaemia in the sporadic Zollinger-Ellison-syndrome may induce gastric carcinoids.

Topics: Adult; Carcinoid Tumor; Female; Gastric Mucosa; Gastrins; Humans; Stomach Neoplasms; Zollinger-Ellison Syndrome

Between 1987 and 1991, 16 patients (13 females, three males; mean age 52.4 [33-73] years) with Zollinger-Ellison syndrome (ZES) were treated according to a standardized surgical concept. The diagnostic work-up consisted of measuring serum gastrin levels, pre-operative localization by ultrasound and abdominal computed tomography, as well as extensive staging by laparotomy. As complete a tumour resection as possible was the aim of treatment in 15 patients, while in one patient it was to reduce the tumour mass. In six patients who had resection of a solitary tumour there was no evidence of recurrence after 6-42 months of follow-up. Exploration of the duodenum made it possible to identify and then remove a small gastrinoma of the duodenal wall in three patients. No gastrinoma was found in one patient despite extensive exploration. In a further four patients the laparotomy was purely exploratory, because diffuse metastasization was found. In four patients the primary tumour and, where present, the regional lymph nodes were removed, but the signs of ZES persisted, i.e. the intervention was merely palliative. In one female patient, reduction of tumour mass was necessary because the symptoms could not be controlled by conservative measures: she died postoperatively from toxic hepatitis. This experience indicates that standardized surgical intervention achieves potentially curative results in nearly 40% of patients. Including the duodenum in the surgical exploration allows the identification of even small gastrinomas of the duodenal wall. It is concluded that all patients with ZES but no evidence of diffuse metastases should undergo surgical treatment.

Topics: Adult; Aged; Algorithms; Clinical Protocols; Diagnostic Imaging; Duodenal Neoplasms; Female; Gastrins; Humans; Laparotomy; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Palliative Care; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Japan; Middle Aged; Prognosis; Reference Standards; Sex Factors; Zollinger-Ellison Syndrome

Evolution of gastrinoma tumoral mass, fasting serum gastrin concentrations, and gastric endocrine cells has been analyzed in 21 patients with the Zollinger-Ellison syndrome committed to long-term omeprazole treatment (up to 7.75 years, median 37 months). Gastrinoma growth was seen in eight patients. Significant increase in serum gastrin was only observed in the group of patients with gastrinoma growth. Fundic argyrophil cell densities were correlated with serum gastrin (r' = 0.68, P = 0.002). Argyrophil and antral gastrin cell densities significantly increased during the survey, but increases were greater in the group with gastrinoma growth (respectively, +136% and +131%) than in the other group (respectively, +34% and +43%). Progression in the degree of argyrophil cell hyperplasia, noted qualitatively, was observed in 11 patients. Fundic carcinoids developed in three of these 11 patients, all three having multiple endocrine neoplasia type 1 (MEN 1). Positive linear individual correlations (r > or = 0.85) between argyrophil cell densities and corresponding durations of omeprazole treatment were found in nine of the 10 patients studied at least three times and who had a clear-cut increase in those cell densities. Thus, increase in serum gastrin and fundic argyrophil cell densities appeared closely associated with gastrinoma growth; however, duration of drug-induced hypochlorhydria may also affect cell proliferation.

Topics: Adult; Aged; APUD Cells; Chi-Square Distribution; Chronic Disease; Female; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Omeprazole; Pancreatic Neoplasms; Prospective Studies; Stomach; Time Factors; Zollinger-Ellison Syndrome

We reviewed the age of presentation, malignant potential, and outcome of gastrinomas and pancreatic tumors in patients with multiple endocrine neoplasm, type 1.. Screening of one very large and one smaller, possibly related family on an island, including serum gastrin estimations and, when indicated, pancreatic ultrasound.. Over 2000 family members and their family physicians were advised on screening procedures.. Data were collected and reviewed retrospectively and prospectively for all medical records, investigations, surgical procedures, and available tissue samples.. Criteria for diagnosis were established for radiological, biochemical, and histological studies.. Sixty-two patients had evidence of gastrinoma or pancreatic neoplasm. In 19 patients the diagnosis was based on demonstration of a tumor. In 21 patients the diagnosis was based on elevated serum gastrin concentration in the absence of demonstrable tumor. None of these patients required gastric surgery if they first underwent parathyroidectomy. In 18 patients the diagnosis was based on the combination of demonstrated pancreatic tumor plus elevated glucagon (two patients), gastrin (11 patients), or insulin (five patients) concentration. Peptic ulcer was difficult to control in seven of the 11 patients with elevated gastrin concentrations plus demonstrated tumor. Four patients had liver metastases that appeared to be secondary to the pancreatic gastrinoma. In patients with insulinomas, the first symptoms occurred before age 20 years. Elevated serum gastrin concentrations were not seen before age 24 years and were observed to occur for the first time in two patients after age 50 years.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Female; Follow-Up Studies; Gastrinoma; Gastrins; Glucagon; Humans; Insulin; Insulinoma; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Prospective Studies; Retrospective Studies; Zollinger-Ellison Syndrome

The aim of the study was to evaluate whether treatment with 200 micrograms/d of the somatostatin analogue octreotide (SMS 201-995) for three months can influence the trophic action exerted by hypergastrinemia on endocrine cells of the oxyntic mucosa, a condition potentially leading to hyperplasia and carcinoid tumors. Endocrine cells were morphometrically investigated in Grimelius silver stained sections of endoscopic biopsies of oxyntic mucosa collected from 13 hypergastrinemic patients with Zollinger-Ellison syndrome (ZES) (n = 5), antral G cell hyperfunction (AGCH) (n = 4) and atrophic gastritis type A (AG-A) (n = 4) before and after 3 months treatment and 3 months after drug discontinuance. The treatment induced a reduction of the volume density (P < 0.015), profile cross sectional area (P < 0.05) and number of cell profiles per unit area (P < 0.015) of argyrophil cells. A rebound of all these parameters was observed 3 months after drug withdrawal with values usually exceeding those at the entry, except in cases of AG-A. The patients' plasma gastrin concentrations presented similar variations showing a significant relation with all morphometric parameters of argyrophil cells. Also, the cell content in alpha subunit of human chorionic gonadotropin was related to the plasma gastrin levels, a finding confirming the close gastrin dependence of the expression of this protein by oxyntic endocrine cells. No significant changes were observed in mucosal somatostatin D cells. These results indicate that variations in circulating gastrin levels are the most likely factor responsible for the hypotrophic effect of octreotide on oxyntic argyrophil cells (mostly corresponding to the ECL cells) of hypergastrinemic patients.

Topics: Adult; Aged; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Octreotide; Parietal Cells, Gastric; Pyloric Antrum; Stomach Diseases; Zollinger-Ellison Syndrome

To identify the best method for determining freedom from disease after gastrinoma resection and for predicting long-term disease-free status in patients with the Zollinger-Ellison syndrome.. Prospective study in consecutive patients.. Referral-based clinical research center.. Eighty-one consecutive patients with the Zollinger-Ellison syndrome who underwent surgical exploration for gastrinoma resection.. Patients were evaluated after gastrinoma resection, before discharge, 3 to 6 months after surgery, and yearly thereafter. Evaluation included secretin provocative testing and fasting serum gastrin determinations. Follow-up examinations after the initial postoperative evaluations included a clinical assessment, acid secretion studies, a calcium provocative test, and various imaging studies.. Most patients (96%) had gastrinomas. Freedom from disease was defined by improved symptoms, reduced acid output and antisecretory drug requirements, and a normal gastrin level, normal imaging studies, and negative gastrin provocative studies. Fifty-two percent of patients (n = 42) were disease-free immediately after surgery, 44% at 3 to 6 months, 42% at 1 year, and 35% by 5 years (mean follow-up, 39 months). The secretin provocative test was the first test to become positive in 45% of patients with a recurrence, the serum gastrin determination was the first test to become positive in 36%, and both tests became positive at the same time in 18%. No recurrence was first detected by imaging studies or by calcium provocative testing. Fasting serum gastrin levels and secretin provocative test results at different postoperative times can be used to predict the probability of a patient remaining disease free at 3 years. Patients with a normal gastrin level and a normal secretin provocative test immediately after surgery had a 3-year disease-free probability of 75%, and normal results on both tests at 6 months, 1 year, and 2 years yielded respective probabilities of 88%, 95%, and 100%.. Both the secretin provocative test and fasting serum gastrin determination are necessary for the early diagnosis of cases of recurrent disease after gastrinoma resection. The calcium provocative test and imaging studies do not detect any recurrences first. Fasting serum gastrin determinations and secretin provocative testing at different postoperative times can be used to predict the probability of a patient remaining disease free at 3 years.

Topics: Adult; Aged; Diagnostic Imaging; Female; Gastrins; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Recurrence; Secretin; Zollinger-Ellison Syndrome

This study reports the effects of 4 and 5-year treatment with octreotide (200 micrograms sc bid) in the Zollinger-Ellison syndrome (ZES). No symptoms related to acid hypersecretion were observed in the four patients throughout the study, and upper GI endoscopy was normal. Basal acid output (BAO) measured 12 h after injection, was below 10 mmol h-1 in three to four patients and previous ranitidine treatment was discontinued. In the fourth case (pretreatment BAO value: 115 mmol h-1), BAO progressively decreased to 42 mmol h-1 after 5 years of octreotide treatment. At the end of the study, serum gastrin levels were 58.5% (30-68) of the pretreatment values and two patients had normal gastrin levels. Peak acid output (PAO) decreased markedly after 2, 4 and 5 years, by 68% (35-89) suggesting that octreotide had exerted an antitrophic effect on parietal cell mass. Diffuse hyperplasia of fundic argyrophil cells present in two patients before octreotide, decreased during the treatment. Mean argyrophil cell density for all patients was not significantly modified. Antral gastrin-cell density was in the normal range. No long-term side effect of octreotide treatment was observed. Although octreotide may not be considered as a substitute for benzimidazoles in the treatment of ZES, its specific properties may be of therapeutic benefit in some ZES patients.

Topics: Adult; Female; Gastric Acid; Gastric Fundus; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Octreotide; Time Factors; Zollinger-Ellison Syndrome

We report an impressive case with Zollinger-Ellison syndrome (ZES), in which stress-induced sympathetic discharge influenced serum gastrin. Our patient was a 35-yr-old female who complained of frequent and massive vomiting (more than 4000 ml of gastric juice) which was aggravated especially by psychosocial stress. Basal hypergastrinemia (1900 pg/ml) was found after the admission. The most striking finding was that laboratory stress dramatically increased serum gastrin (from 1900 to 5400 pg/ml) and plasma noradrenaline (from 180 to 1130 pg/ml). Mental arithmetic stress further enhanced hypergastrinemia (5800 pg/ml) with a concomitant increase in plasma noradrenaline (1240 pg/ml). Neostigmine (10 micrograms/kg im) also increased serum gastrin up to 6100 pg/ml but propranolol (40 micrograms/kg i.v.) reduced these elevations (noradrenaline: 990 pg/ml, gastrin: 5000 pg/ml). In this case, the effect of stress on serum gastrin mimicked the effect of catecholamine infusion in ZES. These findings suggest that psychological stress induces serum gastrin secretion via beta-adrenoceptor with exacerbation of symptoms in some cases with ZES.

Topics: Adult; Female; Gastrins; Humans; Stress, Psychological; Zollinger-Ellison Syndrome

Topics: Calcium; False Negative Reactions; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Information concerning the influence that gastrin may exert on the colon is fragmentary and somewhat controversial. This study analyzed the effect of chronic endogenous hypergastrinemia on cell proliferation and tumor occurrence in the human colonic mucosa.. Twenty-three consecutive hypergastrinemic patients presenting with the Zollinger-Ellison syndrome and 18 normogastrinemic subjects were studied. All had fasting serum gastrin determination, colonoscopy, and cell kinetic measurement in two colonic sites using in vitro 5'-bromodeoxyuridine incorporation.. Macroscopic tumors, one endocrine and five adenomas, were found in 5 of 23 hypergastrinemic patients, without apparent relationship with the level of gastrin. The labeling indices were significantly higher in hypergastrinemic than in normogastrinemic individuals in the right and left colon, (P < 0.002 to P < 0.001) without resulting in colonic cell hyperplasia. There was no correlation between labeling indices and serum gastrin concentrations or duration of hypergastrinemia. The DNA labeling distribution along the crypt was normal in the two groups, without expansion of the proliferative zone towards the surface.. These results showed for the first time that long-lasting endogenous hypergastrinemia is accompanied by increased in vivo cell proliferation in the human colonic mucosa. However, the prevalence of adenomas (17.4%) in patients, all more than 50 years old, may not be different from that in the general population.

Topics: Adenoma; Adult; Aged; Cell Division; Chronic Disease; Colon; Colonic Neoplasms; Colonoscopy; DNA; Female; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Zollinger-Ellison Syndrome

Gastrinomas from 25 patients were examined by immunohistochemistry (IHC) and in situ hybridization histochemistry (ISH). Most patients (84%) presented with the Zollinger-Ellison syndrome. Six had multiple endocrine neoplasia type I (MEN-I). Twelve patients (48%) had duodenal primaries and 11 of 12 of these had metastases to regional lymph nodes and/or liver in spite of the small sizes of the primary tumors (mean size of 0.9 cm). Five patients had pancreatic gastrinomas and eight patients had metastatic tumor in regional lymph nodes or liver at surgery but a primary was not found. IHC and ISH analyses showed that all cases were positive for gastrin protein and 24 of 25 (96%) expressed gastrin mRNA that was easily detected in formalin-fixed, paraffin-embedded tissue sections. Both benign and malignant tumors expressed alpha subunit of human chorionic gonadotropin protein (alpha-HCG). However, only malignant gastrinomas (29%) expressed adrenocorticotropic hormone protein or proopiomelanocortin (POMC) mRNA. ISH and Northern hybridization analysis revealed that chromogranin A mRNA was the most common member of the chromogranin/secretogranin (Cg/Sg) family which was expressed in both benign and malignant gastrinomas. These results indicate that duodenal gastrinomas are common in both sporadic and MEN-1-associated cases, and small duodenal primaries may be associated with extensive regional lymph node and liver metastases. Expression of ACTH/POMC protein and mRNA was consistently associated only with malignant gastrinomas while gastrin protein, gastrin mRNA and Cgs/Sgs mRNAs were readily detected in both benign and malignant gastrinomas.

Topics: Adrenocorticotropic Hormone; Base Sequence; Chromogranins; DNA, Neoplasm; Duodenal Neoplasms; Gastrinoma; Gastrins; Glycoprotein Hormones, alpha Subunit; Humans; Immunohistochemistry; In Situ Hybridization; Molecular Sequence Data; Multiple Endocrine Neoplasia; Oligonucleotide Probes; Pancreatic Neoplasms; Pro-Opiomelanocortin; Proteins; RNA, Messenger; Zollinger-Ellison Syndrome

Topics: Aged; Carcinoma, Small Cell; Gastrins; Humans; Lung Neoplasms; Male; Paraneoplastic Endocrine Syndromes; Stomach Ulcer; Zollinger-Ellison Syndrome

Although gastrinoma resection is generally advocated for patients with the sporadic form of nonmetastatic Zollinger-Ellison syndrome, there is controversy regarding the surgical management of the gastrinoma among patients with multiple endocrine neoplasia type I (MEN-I). Using strict criteria, to date no biochemical cures of the Zollinger-Ellison syndrome lasting greater than 5 months have been achieved by gastrinoma resection among patients with MEN-I. Whereas resections of hepatic metastases have been performed in patients with sporadic gastrinoma, none have been reported among patients with MEN-I. The current report describes a patient with MEN-I, closely followed up for 30 years, in whom enlargement of pancreatic gastrinoma and development of hepatic gastrinoma was observed to occur over 3 years. After preoperative localization, an 80% pancreatectomy and a left lateral segmentectomy of the liver were performed. Sixteen months after the operation, secretin and calcium provocative testing showed that the patient's fasting gastrin and stimulated plasma gastrin concentrations were normal; also, results of computerized tomographic angiography, selective abdominal angiography, and hepatic venous sampling for gastrin after intra-arterial secretin injection were negative for gastrinoma. By achieving a 16-month cure of gastrinoma, this case shows that an aggressive surgical approach can benefit certain patients with gastrinoma who have MEN-I even in the presence of hepatic metastases.

Topics: Angiography; Follow-Up Studies; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia; Neoplasms, Second Primary; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

In a 30-year-old man with Zollinger-Ellison syndrome, the only detectable gastrinoma was in the right liver lobe. Removal of the lobe, without additional gastric surgery, was followed by normalization of the gastrin level. Long-term follow-up confirmed the good result. The usefulness of quick intraoperative gastrin assay is stressed.

Topics: Adult; Follow-Up Studies; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Time Factors; Zollinger-Ellison Syndrome

The influences of multiple endocrine neoplasia type 1 (MEN 1), hypergastrinaemia, age, and sex on gastric endocrine cell densities were studied in 48 patients with the Zollinger-Ellison syndrome of either the sporadic type (n = 31) or associated with MEN 1 (n = 17). The mean fundic argyrophil cell density was higher in women (p < 0.05). It showed no appreciable difference between young and old women but it declined with age in men. The mean argyrophil cell density, when adjusted for sex, was higher (+48.5%, p = 0.06) in patients with Zollinger-Ellison syndrome associated with MEN 1 than in those with sporadic type disease. This measurement was not significantly different between the two groups of patients when antisecretory treatments were considered. In patients with sporadic type disease, fundic argyrophil cells showed a normal pattern (16%) or diffuse (71%) or linear (13%) hyperplasia. In patients with MEN 1 diffuse and linear hyperplasia were of the same order (53% and 47%). Furthermore, fundic argyrophil endocrine tumours developed in five of 17-that is, 29.5% of patients with associated MEN 1 while none was seen in patients with sporadic type disease. These tumours showed an exclusive or prominent enterochromaffin like cell population. Antral gastrin and somatostatin cell densities and fasting serum gastrin concentrations were similar in the two groups of patients with Zollinger-Ellison syndrome. Whatever the underlying mechanism for carcinoidosis, the risk of developing fundic enterochromaffin like cell tumours in Zollinger-Ellison syndrome patients who present with MEN 1 is probably higher than was initially estimated and suggests that regular follow up of these patients is necessary.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Cell Count; Female; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Sex Factors; Stomach; Zollinger-Ellison Syndrome

The efficacy of omeprazole increases during the first few days of administration, suggesting that long-term maintenance dose requirements in patients with Zollinger-Ellison syndrome may be lower than those initially established by upward titration. Long-term maintenance doses of omeprazole were prospectively reduced in 37 patients who had been taking omeprazole for 22 +/- 4 months. Successful reduction was defined as reduction to 20 mg once or twice daily with an absence of symptoms, endoscopy without evidence of active acid-peptic disease, and a gastric acid output of < 10 mEq/h. Sixty-eight percent of patients (25/37) were successfully reduced to 20 mg of omeprazole once (18/24) or twice daily (7/13). Ninety-five percent of patients (20/21) without multiple endocrine neoplasia type I, severe gastroesophageal reflux disease, or previous partial gastrectomy had safe reductions of doses. It is concluded that the currently used omeprazole maintenance doses in patients with Zollinger-Ellison syndrome are too high and advocated that the initial dose still be established by acute daily upward titration followed by gradual reduction once control of acid output has been achieved.

Topics: Adult; Aged; Female; Gastric Acid; Gastrins; Humans; Longitudinal Studies; Male; Middle Aged; Omeprazole; Prospective Studies; Stomach; Zollinger-Ellison Syndrome

The case of a patient who had Zollinger-Ellison syndrome caused by a primary peripancreatic lymph node gastrinoma is presented. Accompanying diffuse pancreatic islet cell hyperplasia, a well-documented occurrence in hypergastrinemia, was present. A perforated esophageal ulcer in a Barrett's esophagus led to right-sided necrotizing pleuritis, septicemia, and death. The diffuse parathyroid hyperplasia also noted in the patient is thought to be secondary to chronic hypertensive renal failure rather than MEN-I syndrome.

Topics: Aged; Female; Gastrinoma; Gastrins; Humans; Immunoenzyme Techniques; Lymph Nodes; Neoplasms, Second Primary; Pancreas; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Biopsy specimens from the oxyntic mucosa were obtained on 210 occasions from 76 patients with the Zollinger-Ellison syndrome (ZES) before and during omeprazole treatment. One-micrometer sections were examined by light microscopy, and in 5% linear hyperplasia of endocrine cells was observed. Morphometry was carried out in 91 of the specimens and showed a significant increase of the mean endocrine cell density in comparison with both young, healthy subjects and patients suffering from active peptic ulcer disease (PUD). No metaplasia, dysplasia, or neoplasia was detected in patients with ZES, and the mean mucosal thickness and parietal cell density remained normal. The parietal cells often displayed endosome-like structures, and occasionally there were lingulate cytoplasmic projections into the gland lumen. Electron microscopic morphometry was carried out in specimens from nine patients with ZES and did not show any significant differences in the parietal cells in comparison with healthy subjects.

Topics: Adolescent; Adult; Age Factors; Aged; Biopsy; Cell Count; Evaluation Studies as Topic; Female; Gastrins; Humans; Hyperplasia; Male; Microscopy, Electron; Middle Aged; Omeprazole; Parietal Cells, Gastric; Surface Properties; Zollinger-Ellison Syndrome

Duodenal gastrinomas producing Zollinger-Ellison syndrome (ZES) are rarely imaged on preoperative studies. Measurement of serum gastrin levels by transhepatic portal venous sampling (PVS) or by sampling from hepatic veins after intraarterial secretin injection have been advocated as useful tests to identify these tumors before operation.. As part of a prospective study, selective intraarterial secretin injection has been performed in 36 consecutive patients with ZES, PVS has been performed in 30 of these patients, and the results have been compared.. Gastrinomas were found at laparotomy in 33 of 36 patients (92%). Duodenal tumors were found in 18 patients (50%). The remaining patients had liver, pancreatic, or nodal disease (n = 15). Thirty-two of 36 patients (89%) had positive results with intraarterial secretin injection study, whereas 18 of 30 (60%) had a positive PVS gradient (p = 0.02, Fisher's exact test). The most common positive gradient with intraarterial secretin injection was found with injections of the gastroduodenal artery, and the most common positive gradient with PVS was found in the inferior pancreaticoduodenal (IPDV) or superior pancreaticoduodenal vein (SPDV). Fourteen of 18 (78%) patients with duodenal gastrinomas had a positive GDA injection, whereas five of 18 (28%) without duodenal tumors had a positive GDA injection (p = 0.006). Five of 16 patients with duodenal gastrinomas had a positive gradient in the IPDV or SPDV, whereas four of 14 without duodenal tumors had a positive gradient in the IPDV or SPDV (not significant).. Intraarterial secretin injection is more sensitive than PVS at localizing duodenal gastrinomas and should replace PVS in patients with ZES and occult tumors.

Topics: Adult; Duodenal Neoplasms; Female; Gastrinoma; Gastrins; Humans; Injections, Intra-Arterial; Laparotomy; Male; Middle Aged; Portal Vein; Prospective Studies; Secretin; Zollinger-Ellison Syndrome

The biologic gastrin activity in serum from 14 patients with the Zollinger-Ellison syndrome was assessed by the stimulation of histamine release and acid secretion from the isolated vascularly perfused rat stomach and compared with the immunologic activity as determined by radioimmunoassay using an antibody directed towards the active site of the gastrin molecule. Biologic gastrin activity assessed by the stimulation of histamine release was more closely correlated to immunologic gastrin activity than biologic activity assessed by the stimulation of gastrin acid secretion. This study does not contradict the concept that gastrin stimulates acid secretion at least partly by releasing histamine and also shows that the immunologic gastrin activity determined with the help of an antibody directed towards the active site reflects biologic activity.

Topics: Aged; Animals; Biological Assay; Female; Gastric Mucosa; Gastrins; Histamine; Humans; In Vitro Techniques; Male; Middle Aged; Radioimmunoassay; Rats; Rats, Wistar; Zollinger-Ellison Syndrome

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

Nine patients with Zollinger-Ellison syndrome were treated with octreotide acetate (100 micrograms delivered subcutaneously three times daily) and followed up for 1 to 48 months. Serum gastrin levels were obtained at predetermined intervals. All patients had elevated baseline fasting gastrin levels (greater than 150 ng/L [greater than 150 pg/mL]). One month after administration of octreotide, gastrin levels were in the reference range for five (62%) of eight patients, and a mean gastrin suppression rate of 76% was achieved (ie, values were a mean of 76% less than baseline values). One year after administration of octreotide, five (71%) of seven evaluable patients had gastrin levels of less than 200 ng/L (200 pg/mL), and the mean gastrin suppression rate was more than 80% for these seven patients. During the second year, control at these levels was maintained in four patients; one patient continued to have controlled levels for 42 months. Complete symptomatic response occurred in seven patients (78%), and partial response in two patients (22%). All six patients with diarrhea before treatment were cured of it. Octreotide acetate provides efficacious long-term suppression of elevated gastrin levels and excellent symptomatic relief in patients with Zollinger-Ellison syndrome.

Topics: Abdominal Pain; Adolescent; Aged; Diarrhea; Fasting; Female; Follow-Up Studies; Gastrinoma; Gastrins; Humans; Injections, Subcutaneous; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Prospective Studies; Zollinger-Ellison Syndrome

A 40-year-old woman had persistent Zollinger-Ellison syndrome despite excision of a 4-cm duodenal gastrinoma. Localizing studies including ultrasonography, computed tomography, magnetic resonance imaging, duodenal endoscopy, endoscopic ultrasonography, and intraoperative endoscopic transillumination of the duodenum failed to detect a tumor. Selective intra-arterial methylene blue injection was used to identify a 6-mm gastrinoma in the duodenum, which was locally excised. Postoperatively, the patient had a negative secretin provocative test result. This novel method uses selective arterial secretin injection with hepatic venous gastrin sampling to identify the vessel feeding the gastrinoma. An angiographic catheter is then positioned in this artery. At laparotomy, methylene blue is injected through this catheter to selectively stain the gastrinoma, facilitating its identification. Selective intra-arterial methylene blue injection can enhance intraoperative detection of small gastrinomas and may improve the rate of curative resection in the Zollinger-Ellison syndrome. Further evaluation of this novel localizing technique is warranted.

Topics: Adult; Endoscopy; Female; Gastrinoma; Gastrins; Humans; Injections, Intra-Arterial; Intraoperative Period; Magnetic Resonance Imaging; Methylene Blue; Pancreatic Neoplasms; Secretin; Tomography Scanners, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

Gastrin immunocytochemistry and non-radioactive in situ hybridization, using biotinylated oligonucleotide probes, for gastrin mRNA have been used for studying a retrospective material of six gastrin-producing (Zollinger-Ellison) tumors. Hybridization results for gastrin mRNA were positive in all six, while gastrin immunoreactivity could be detected in five tumors. In one of the patients, different areas of the same tumor displayed differences in immunoreactivity to gastrin, but were uniformly hybridization positive. Weak hybridization signals were detected in liver metastases from a necropsy case, while the gastrin immunostaining was more pronounced. The results show that non-radioactive hybridization methods are applicable to routine clinical specimens stored for as long as 16 years and that in situ hybridization may be a useful complement to immunocytochemical diagnosis, particularly in cases where high synthesis and little storage of hormonal products occur.

Topics: Base Sequence; Gastric Mucosa; Gastrinoma; Gastrins; Humans; Immunoenzyme Techniques; Molecular Sequence Data; Nucleic Acid Hybridization; Pancreatic Neoplasms; Pyloric Antrum; RNA, Messenger; Zollinger-Ellison Syndrome

Fasting serum gastrin levels greater than 1000 pg/ml are said to establish the diagnosis of gastrinoma in a patient with peptic ulcer disease. The authors observed a patient with recurrent peptic ulcer disease, diarrhea, and a fasting serum gastrin of 1044 pg/ml who had a gastrocolic fistula, not the Zollinger-Ellison syndrome. The provocative tests of gastrin secretion, including secretin infusion and standard meal test, were helpful in ruling out a gastrinoma. This is the first reported association of gastrocolic fistula and hypergastrinemia. The patient demonstrates that the differential diagnosis of markedly elevated serum gastrin should be expanded to include gastrocolic fistula.

Topics: Adult; Colonic Diseases; Diagnosis, Differential; Female; Gastric Fistula; Gastrins; Humans; Intestinal Fistula; Stomach Ulcer; Zollinger-Ellison Syndrome

All 95 portal venous sampling (PVS) procedures performed in patients with Zollinger-Ellison syndrome in the past 10 years at the authors' institution were reviewed. It was possible to catheterize at least one branch of the pancreaticoduodenal venous arcade in all but two procedures (98%). The highest concentration of gastrin was found in a selective sample from the pancreaticoduodenal venous arcade or the transverse pancreatic vein in 56 of 91 procedures (62%). Selective sampling of pancreatic head veins yielded a gastrin gradient sufficient for localization in 60 patients (63%). Among 55 solitary sporadic gastrinomas identified at surgery, PVS allowed correct localization of the tumor in 32 (58%); if selective samples had not been obtained, only eight (15%) would have been localized (P less than .0005). Sensitivity was the same for tumors in the gastrinoma triangle (64%) and the body or tail of the pancreas (60%). There were no false-positive results. The overall complication rate was 20%, but most complications were abdominal pain lasting 3 days or less. Six patients (6%) had serious complications.

Topics: Abdominal Pain; Blood Specimen Collection; Catheterization, Peripheral; Duodenum; Female; Gastrins; Humans; Male; Middle Aged; Pancreas; Phlebography; Sensitivity and Specificity; Veins; Zollinger-Ellison Syndrome

The clinical features, diagnostic methods, management and survival in 16 cases of Zollinger-Ellison syndrome encountered in Northern Ireland between the years 1970 and 1988 are described. While the majority of patients in the first decade of the study period had surgical treatment, those presenting in the latter period have been managed with medical therapy in the form of H2-receptor antagonists or omeprazole. The increasing use of these agents seems to be altering the severe clinical features of this condition, reducing the indications for surgery and maintaining patients, with or without evidence of metastatic disease, in clinical remission.

Topics: Adult; Aged; Female; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Omeprazole; Retrospective Studies; Zollinger-Ellison Syndrome

Specimens from the pancreas and duodenum of 26 patients with sporadic Zollinger-Ellison syndrome (ZES) and 18 patients with multiple endocrine neoplasia type 1 (MEN-1) and hypergastrinemia (17 with ZES) were screened immunocytochemically for gastrinomas. Location, size, multicentricity, and malignancy of the gastrinomas were evaluated. The MEN-1 patients had gastrinomas in the duodenum (nine of 18), pancreas (one of 18), and periduodenal lymph nodes (two of 18). No gastrinoma was identified in six patients. Most duodenal gastrinomas were multiple (five of nine) and smaller than 0.6 cm (six of nine). Lymph node metastases were present in eight of 12 patients. All 26 patients with sporadic ZES had a solitary gastrinoma; 14 were found in the pancreas and had a diameter greater than 2 cm. Ten patients had a duodenal gastrinoma, two with a diameter less than 0.6 cm. In two patients, only periduodenal "lymph node gastrinomas" were detected. Eighteen of the sporadic gastrinomas were malignant. These results suggest that duodenal location and multicentricity of gastrinomas are associated with the MEN-1 syndrome, and solitary gastrinomas, either in the pancreas or the duodenum, are predominantly seen in sporadic ZES.

Topics: Duodenal Neoplasms; Gastrinoma; Gastrins; Humans; Immunohistochemistry; Liver Neoplasms; Lymphatic Metastasis; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

A case of Zollinger-Ellison syndrome of multiple endocrine neoplasia type 1 (MEN 1) origin with hyperparathyroidism and with a rise in serum gastrin due to an unusual parathyroid "gastrinoma" has been investigated. The patient had multiple endocrine tumours (pituitary and parathyroid), but no evidence of pancreatic or duodenal gastrin-producing neoplasm. Radio-immunoassay, immunohistochemistry and electron microscopy showed gastrin in one parathyroid adenoma. These findings, together with a decrease of gastrinaemia after parathyroidectomy suggest that true gastrin was produced by parathyroid tumour cells and that they themselves may be the origin of the hypergastrinaemia. Our ultrastructural investigation extends these observations and the results are discussed.

Topics: Adenoma; Female; Gastrins; Humans; Immunohistochemistry; Microscopy, Electron; Middle Aged; Multiple Endocrine Neoplasia; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Zollinger-Ellison Syndrome

The results of gastric secretory studies in 192 cases of recurrent ulcer after surgery for duodenal ulcer were analyzed and compared with the secretory data collected in a control group of 74 duodenal ulcer patients who had undergone various forms of gastric surgery, but who did not develop a recurrent ulcer (controls). The patients studied comprised 46 cases of recurrent ulcer after partial gastrectomy, 10 cases of recurrent ulcer after partial gastrectomy and bilateral truncal vagotomy, 56 cases of recurrent ulcer after truncal vagotomy and drainage, 52 cases of recurrent ulcer after highly selective vagotomy, and finally 28 cases in which the recurrent ulcer led to the diagnosis of the Zollinger-Ellison syndrome. The entire study was based upon an analysis of the basal acid output, the response to maximal stimulation by pentagastrin or by histalog and by insulin in the case of previous vagotomy, and finally on an assessment of basal serum gastrin. The analysis has suggested minimal secretory levels with discriminative values useful for the postoperative diagnosis of recurrent ulcer and for an assessment of the completeness of vagotomy (ratio PAO Insulin/PAO pentagastrin or histalog). Moreover, an analysis of various elements of the sequential basal pentagastrin-insulin test permitted us to approach the pathophysiological mechanism responsible for ulcer recurrence, and to identify suitable criteria for selection of the best treatment.

Topics: Adult; Duodenal Ulcer; Female; Gastrectomy; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Recurrence; Vagotomy; Zollinger-Ellison Syndrome

Topics: Animals; Carcinoid Tumor; Female; Gastrins; Humans; Neoplasms, Hormone-Dependent; Rats; Stomach; Stomach Neoplasms; Zollinger-Ellison Syndrome

The influence of gastric resection on the Zollinger-Ellison syndrome (ZES) in eight children was first reported to the Central Surgical Association 26 years ago. That report showed that the three children who had less than total gastrectomy were all dead with complications of gastric acid hypersecretion, although the five children who had total gastrectomy were living and well. During the past quarter of the century, the development of effective gastric acid inhibitors has prompted a greater emphasis on medical management in the ZES. The role of the surgeon and total gastrectomy remains controversial. Follow-up of the five young patients who had total gastrectomy shows that only one patient was dead with tumor 14 years after total gastrectomy and that the remaining four patients were alive 30, 29, 28, and 27 years, respectively, after total gastrectomy. Growth and activity have been near normal. All patients have had proven metastatic islet-cell carcinoma documented at some time in the course of the disease (lymph nodes in three patients and liver metastasis in two patients). Only one of the four living patients with total gastrectomy had a normal serum gastrin level and no apparent tumor. Gastrinoma tumor growth appears to be less aggressive in children than in adults. Complete excision of gastrinomas is possible in some patients with ZES. When hypergastrinemia persists, total gastrectomy may be preferable to lifelong medical management with gastric acid inhibitors in children and young adults with ZES.

Topics: Adolescent; Child; Female; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Male; Survival Analysis; Zollinger-Ellison Syndrome

Since Helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer, infection with this organism has been implicated in the pathogenesis of this common disease. We postulated that if H. pylori is pathogenic in the usual type of duodenal ulcer, it should be less common when duodenal ulcer has another, specific etiology, such as Zollinger-Ellison syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger-Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with chronic duodenal ulcer without such a diagnosis. All subjects, who were matched for age and sex, had undergone elective gastric resections. Gastric tissues were stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis. The frequency of H. pylori in patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with duodenal ulcer (16/18; P less than 0.02). Moreover, chronic antral gastritis scores were higher in patients with duodenal ulcer (P less than 0.01). In Zollinger-Ellison syndrome, peak acid output was lower in patients positive (median 22 meq/30 min) compared to those negative for H. pylori (median 32 meq/30 min; P less than 0.02) but serum gastrin was correspondingly lower in patients positive for H. pylori (P less than 0.05). H. pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology, such as acid hypersecretion in Zollinger-Ellison syndrome. H. pylori infection in Zollinger-Ellison syndrome may also be associated with decreased gastric acid secretion.

Topics: Adolescent; Adult; Aged; Child; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Helicobacter pylori (previously Campylobacter pylori) is almost invariably associated with chronic duodenal ulcer disease. The relationship between H. pylori infection and duodenal ulcer in Zollinger-Ellison syndrome is unknown. We investigated the frequency of H. pylori infection in Zollinger-Ellison syndrome and also what effect H. pylori infection had on gastric function in patients with Zollinger-Ellison syndrome. H. pylori infection was diagnosed based on a specific serologic (ELISA) assay based on high-molecular-weight cell-associated proteins of H. pylori. We studied 20 patients with Zollinger-Ellison syndrome; 15 men and 5 women ranging in age from 24 to 71 years, median age 51. Six Zollinger-Ellison syndrome patients had H. pylori infection compared to 100 consecutive patients with chronic recurrent duodenal ulcer disease (P less than 0.05). Pretreatment basal acid output in Zollinger-Ellison syndrome patients ranged from 7.9 to 95.0 mmol/hr, median 35.2. Pentagastrin-stimulated maximal acid output ranged from 8.5 to 132 mmol/hr; median 52.7. Acid secretion was lower in the H. pylori-infected patients than the uninfected patients (BAO 24.5 +/- 6.5 vs 45.4 +/- 6.6, and MAO 44.3 +/- 11.8 vs 67.9 +/- 10.7, for H. pylori infected vs uninfected patients, respectively). The difference in BAO was statistically significant (P less than 0.05). The present results indicate that H. pylori is not a major contributing factor in duodenal ulcer associated with Zollinger-Ellison syndrome. The association of a reduced BAO with H. pylori suggests that these findings may be related.

Topics: Adult; Aged; Chronic Disease; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Recurrence; Zollinger-Ellison Syndrome

The salient contributions of the Zollinger-Ellison syndrome have made it unique. No pancreatic endocrine tumor described before (insulinoma) or subsequently (glucagonoma, somatostatinoma, vipoma, pancreatic-polypeptidoma) has been the topic of such a variety of studies, or has been such an inspiration and rich source of new ideas for investigation and ultimate improvement in patient care.

Topics: Gastrinoma; Gastrins; Humans; Lymphatic Metastasis; Pancreatic Neoplasms; Peptic Ulcer; Research; Zollinger-Ellison Syndrome

The secretin stimulation test has become the preferred provocative test in suspected cases of Zollinger-Ellison syndrome. A pure secretin preparation, a gastrin-specific radioimmunoassay, and an appropriate sampling sequence are important for the proper interpretation of this test. Gastric acid analysis is necessary in the assessment of hypergastrinemia to confirm acid hypersecretion and exclude achlorhydria. When properly performed and interpreted, the secretin provocation test offers a safe, expeditious, and reliable means of evaluating patients with hypergastrinemia.

Topics: Calcium; Gastrins; Humans; Injections, Intravenous; Radioimmunoassay; Reference Values; Secretin; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Injections, Intra-Arterial; Secretin; Zollinger-Ellison Syndrome

Posttranslational processing is an important phase of the expression of most eucaryotic genes in terms of functional proteins. Among these, secretory proteins and peptides are of particular interest for clinical chemists, since diagnostic measurements of circulating proteins and peptides constitute a major discipline in clinical chemistry. The posttranslational covalent maturation of secretory proteins and peptides involves multiple enzymatic modifications of the corresponding proproteins along the intracellular secretory pathway. During the eighties, an increasing amount of evidence has indicated that sick secretory cells fail to process their secretory products normally. The diseased cells therefore fail to process their secretory products normally. The diseased cells therefore release also incompletely processed precursors and processing-intermediates. In order to measure the degree of disease, assays that measure proteins and peptides independent of the degree of processing are therefore desirable. We have now designed a new analytical principle, according to which secretory proteins, peptides and their precursors can be accurately quantitated irrespective of the degree of processing. This principle, named processing-independent analysis (PIA), is generally applicable to all cellular synthesized substances. The principle has been applied to and developed first for a well-defined secretory peptide system, progastrin and its products. Using this model, the results obtained so far confirm the diagnostic superiority of processing-independent analysis in comparison with conventional assays for bioactive peptides.

Topics: Amino Acid Sequence; Animals; Chemistry, Clinical; Clinical Laboratory Techniques; Duodenal Ulcer; Gastrinoma; Gastrins; Humans; Molecular Sequence Data; Peptides; Protein Precursors; Protein Processing, Post-Translational; Proteins; Radioimmunoassay; Zollinger-Ellison Syndrome

Ninety-nine carcinoid tumors of the duodenum were studied. Seventy-seven patients were followed up for a mean period of 65 months, 20 tumors were autopsy findings, and two patients were unavailable for follow-up. Sixteen tumors (21%) produced metastases, all discovered initially; 3 patients (4%) died from metastatic disease (mean survival, 37 months postoperatively). Features associated with metastatic risk were involvement of muscularis propria, size greater than 2 cm, and the presence of mitotic figures. For 51 tumors, there was no correlation between immunohistochemical somatostatin and history of diarrhea, cholelithiasis, or diabetes mellitus (somatostatin syndrome). Five tumors were associated with Zollinger-Ellison syndrome and had immunohistochemical gastrin, but in the others there was no correlation between ulcer disease and gastrin positivity. Duodenal carcinoids are indolent, especially when small and localized to the submucosa. Immunohistochemical identification of somatostatin and gastrin has little clinical relevance.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Carcinoid Tumor; Duodenal Neoplasms; Endoscopy; Female; Follow-Up Studies; Gastrins; Humans; Hydroxyindoleacetic Acid; Immunohistochemistry; Male; Middle Aged; Predictive Value of Tests; Prognosis; Somatostatin; Staining and Labeling; Zollinger-Ellison Syndrome

In 1983, all trials of omeprazole in humans were stopped because rats given the drug developed gastric endocrine cell hyperplasia and carcinoid tumors. Further studies in rats showed that drug-induced achlorhydria and hypergastrinemia caused these changes. Because data in humans are limited, we compared the numbers of endocrine cells, as judged by silver staining (argyrophilia), in the gastric mucosa of patients with Zollinger-Ellison syndrome, who are hypergastrinemic, and in normogastrinemic patients with idiopathic acid-peptic diseases. In addition, we analyzed the number of gastric endocrine cells in patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years. Patients with Zollinger-Ellison syndrome had 15.7% +/- 6.9% argyrophil cells in biopsies of gastric oxyntic mucosa, and patients with idiopathic acid-peptic disease had 7.8% +/- 2.3% (P less than 0.01). In patients with Zollinger-Ellison syndrome, the percentage of argyrophil cells was not related to serum gastrin concentration, duration of symptoms, time since diagnosis, basal or maximal acid output, extent of tumor, or age. There was a tendency for patients with multiple endocrine neoplasia type 1 to have a greater percent of argyrophil cells than patients with sporadic Zollinger-Ellison syndrome. Considering the biopsies from both normogastrinemic and hypergastrinemic patients, there was a significant relationship between the percentage of argyrophil cells and the serum concentration of gastrin (P less than 0.01). Patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years developed no significant changes in percentage of argyrophil cells, no carcinoid tumors, and no changes in serum concentrations of gastrin. The present study shows that patients with Zollinger-Ellison syndrome have an increased percentage of argyrophil cells in oxyntic mucosa and that omeprazole does not increase this percentage. In periods of up to 3 years, omeprazole had no effects on gastric morphology in patients with Zollinger-Ellison syndrome.

Topics: Adult; Cell Count; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Omeprazole; Parietal Cells, Gastric; Peptic Ulcer; Staining and Labeling; Time Factors; Zollinger-Ellison Syndrome

Topics: Female; Gastrinoma; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

In patients with multiple endocrine neoplasia type 1 (MEN-1), gastrinomas are common and thought to occur predominantly in the pancreas. We describe eight patients with MEN-1 and hypergastrinemia (seven with the Zollinger-Ellison syndrome) in whom we searched for neuroendocrine tumors in the pancreas and duodenum. Tumors were found in the proximal duodenum in all eight patients: solitary tumors (diameter, 6 to 20 mm) in three patients and multiple microtumors (diameter, 2 to 6 mm) in the other five. Paraduodenal lymph-node metastases were detected in four patients. Immunocytochemical analysis revealed the presence of gastrin in all the duodenal tumors and in their lymph-node metastases. In contrast, no immunoreactivity for gastrin was present in the endocrine tumors found in the seven pancreatic specimens available for study, except for one tumor with scattered gastrin-positive cells. In four of the six patients whose duodenal gastrinomas were removed, serum gastrin levels returned to normal; in the other two patients gastrin concentrations decreased toward normal. We conclude that in patients with MEN-1 and the Zollinger-Ellison syndrome, gastrinomas occur in the duodenum, but the tumors may be so small that they escape detection.

Topics: Adult; Aged; Duodenal Neoplasms; Female; Gastrinoma; Gastrins; Humans; Immunohistochemistry; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Until two decades ago the Zollinger-Ellison syndrome (ZES) was difficult to diagnose and stage accurately. Total gastrectomy was often the ultimate treatment. Improvements in the measurement of serum gastrin and in radiographic imaging have greatly improved the precision of diagnosis and staging. Treatment with histamine-2 receptor antagonists and proton pump blockers have eliminated the need for gastrectomy, and current surgical intervention is directed at cure through removal of the localized gastrinoma. We reviewed the management of eight patients with this diagnosis seen at Henry Ford Hospital from 1983 to 1988. Time from first presentation to diagnosis varied from two months to ten years (mean 4.5 years) and four patients had peptic ulcer surgery before the ZES diagnosis. A high level of suspicion is required in order to make early diagnosis. Prior to elective peptic ulcer surgery, all patients should have serum gastrin assay to exclude ZES.

Topics: Adult; Aged; Female; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

A study relating to gastrin release from gastrinoma cells by neuromedin B and C-terminal decapeptide of gastrin releasing peptide (GRP-10) has not yet been reported. Therefore, we studied the effects of neuromedin B and GRP-10 on gastrin release from cultured dispersed cells prepared from both the primary tumor in the pancreas and the metastatic tumor in the liver from a case of malignant Zollinger-Ellison syndrome. Both the primary and metastatic tumors obtained by a curative operation contained similar concentrations of gastrin and glucagon, whereas the primary tumor contained 10 times more insulin than the metastatic tumor. Gastrin release from cultured cells of both tumors was suppressed by 0.1 and 10 nM neuromedin B and tended to be suppressed by 0.1-10 nM GRP-10. However, insulin release from cultured cells of the pancreatic tumor was stimulated by GRP-10, but not by neuromedin B. These results might suggest that receptor function for the bombesin family peptides is abnormal in gastrinoma cells in both primary and metastatic tumors, and that a major source of insulin secretary cells is the contaminated normal islet cells in the primary tumor.

Topics: Adult; Bombesin; Female; Gastrins; Humans; Insulin; Insulin Secretion; Neurokinin B; Peptide Fragments; Tumor Cells, Cultured; Zollinger-Ellison Syndrome

The mechanism for secretin-induced gastrin release in the Zollinger-Ellison syndrome is uncertain. We evaluated whether the stimulatory effect of intravenous secretin on gastrin release was partly mediated through a beta-adrenergic stimulatory mechanism. Serum gastrin concentrations and heart rate were monitored in six patients with the Zollinger-Ellison syndrome. Secretin (2 clinical units/kg) increased mean serum gastrin concentrations from 1558 pg/ml basally to a peak of 3683 pg/ml (136% above baseline). This increase was not altered by pretreatment with 2 mg of propranolol intravenously, a dose which in previous studies blocked terbutaline-induced gastrin release. Secretin increased heart rate by 14 beats/min (20% above base-line) and this also was not altered by propranolol pretreatment. Thus, the stimulatory effects of secretin on gastrinoma cells and the heart do not appear to be mediated by beta-adrenergic receptors.

Topics: Adult; Aged; Gastrins; Heart Rate; Humans; Male; Middle Aged; Propranolol; Radioimmunoassay; Secretin; Tachycardia; Zollinger-Ellison Syndrome

The effect of epinephrine on the plasma gastrin level was investigated in three patients with Zollinger-Ellison syndrome (ZES) and in 14 normal subjects. Two ZES patients had undergone total gastrectomy, and the third had undergone subtotal gastrectomy before our study. A significant increase in plasma gastrin, from 23 +/- 5 pg/ml to 53 +/- 20 pg/ml, in response to intravenous epinephrine (40 ng/kg.min), was observed in the normal subjects. This response was completely abolished by beta-blockade. In the ZES patients, epinephrine (40 ng/kg.min) also resulted in an increase in the plasma concentration of gastrin. The basal and maximum concentrations of gastrin were 580 and 1680 pg/ml in patient 1, 145000 and 320000 pg/ml in patient 2, and 200 and 1800 pg/ml in patient 3, respectively. beta-Adrenergic blockade suppressed the epinephrine-stimulated gastrin release in these patients as well. Graded intravenous doses of epinephrine given to the ZES patients resulted in elevation of the plasma gastrin in a dose-dependent manner. Insulin hypoglycemia caused an increase in both plasma epinephrine and plasma gastrin in ZES patients and normal subjects. A significant correlation between plasma gastrin and epinephrine during insulin hypoglycemia was observed in both groups. Exercise, with use of a bicycle ergometer, resulted in an increase in plasma epinephrine. An increase in plasma gastrin with exercise was observed in the ZES patients, and this was also suppressed by beta-blockade. The results suggest that gastrinoma cells, like normal G cells, are equipped with beta-adrenergic receptors that regulate gastrin release.

Topics: Adult; Epinephrine; Female; Gastrinoma; Gastrins; Humans; Male; Physical Exertion; Receptors, Adrenergic, beta; Zollinger-Ellison Syndrome

Three Zollinger-Ellison syndrome patients were treated during the period January 1977 to June 1978. The first patient is in good health 11 years 3 months after a total gastrectomy as is the second patient, 11 year after the enucleation of a cephalo-pancreatic gastrinoma. However the third patient died from malignancy 5 years after a total gastrectomy and enucleation of a cephalo-pancreatic gastrinoma followed by therapeutic cycles with streptozotocin and 5-fluorouracil. The decline in the Zollinger-Ellison syndrome over the last ten years is examined and the type of surgical treatment is discussed. Total gastrectomy once advocated as the preferred treatment, is now reappraised because of the effectiveness of medical therapy in controlling ulcers and because of the frequent malignancy of pancreatic gastrinomas.

Topics: Adult; Carcinoma, Hepatocellular; Female; Follow-Up Studies; Gastrins; Humans; Italy; Liver Neoplasms; Male; Middle Aged; Zollinger-Ellison Syndrome

In two patients with malignant gastrinoma and the Zollinger-Ellison syndrome, we were able to use selective arterial stimulation with secretin as a technique to localize the lesions accurately, allowing resection. The technique of selected arterial secretin stimulation is one of measuring variations in gastrin levels in both the hepatic vein and a peripheral artery at specified times after injection of secretin into a specific artery. When the criteria for localization have been met, one can plot the presence of the gastrinoma within the blood supply of the injected artery and, using angiograms, thus accurately localize the lesion. This method promises to be a valuable additional tumor-localizing procedure, particularly when gastrinomas are extrapancreatic.

Topics: Adenoma, Islet Cell; Angiography; Drug Evaluation; Female; Gastrinoma; Gastrins; Hepatic Veins; Humans; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Secretin; Time Factors; Zollinger-Ellison Syndrome

The clinical presentation of Zollinger-Ellison syndrome (ZES) is the result of gastrin hypersecretion and may be modified by secondary peptide hypersecretion. Treatment is medical (H2-blockers) or surgical (tumor excision and total gastrectomy). H2-blocker escape occurs up to 23 per cent and surgical mortality ranges to 15 per cent. Treatment of advanced disease has limited success. Sandostatin (SMS 201-995) has been shown to decrease basal gastrin and gastric acid secretion in ZES. We hypothesized that SMS would suppress basal and provoked gastrin and secondary peptide secretion in ZES. A patient with refractory, metastatic gastrinoma underwent provocative testing (test meal, calcium infusion, secretion bolus and tolbutamide bolus). Thirteen peptides were drawn at set intervals during these provocative tests. Testing was repeated during SMS therapy (100 micrograms subcutaneously three times per day). Gastrin, pancreatic polypeptide (PP) and glucagon levels were elevated at baseline. SMS suppressed all three peptides (mean 74 per cent) (p less than 0.05). Gastrin, PP and glucagon were provoked by all four tests (means above baseline, 19, 155 and 138 per cent, respectively). Gastrin-releasing peptide, gastric inhibitory peptide and insulin were provoked by calcium infusion (427, 306 and 162 per cent above baseline, respectively). SMS suppressed 14 of 15 of these peaked-provoked peptide levels (mean 72.5 per cent, p less than 0.05). Gastric analysis during calcium infusion showed SMS suppression of hourly gastric secretory volume by 77.5 per cent and of acid production (milliequivalents of acid) by 87.5 per cent. During a 20 month follow-up period, the patient was maintained on SMS, 200 micrograms subcutaneously three times per day. She has remained asymptomatic. Interval peptide profiles at two, eight and 18 months show normal gastrin, PP and glucagon levels. A computed tomographic scan at eight months shows a remarkable regression of primary and metastatic tumor. Regrowth, however, was noted at 19 months. SMS may be useful in ZES by suppressing basal and provoked gastrin and secondary peptide secretion and may occasionally give palliation by yielding temporary tumor registration.

Topics: Aged; Calcium; Female; Food; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Insulin Secretion; Octreotide; Pancreatic Polypeptide; Secretin; Tolbutamide; Zollinger-Ellison Syndrome

Most authorities feel that diagnosis of the Zollinger-Ellison syndrome is established when the serum gastrin level is greater than 1000 pg/mL (1000 ng/L) in a patient with gastric acid hypersecretion and clinical manifestations consistent with the diagnosis. A patient with recurrent peptic ulcer disease is reported who was thought to have had the Zollinger-Ellison syndrome based on two serum gastrin level measurements greater than 1000 pg/mL (1000 ng/L). Subsequent evaluation revealed the gastrin elevation to be spurious because the sample was hyperlipidemic. Lipemic serum samples may yield falsely elevated serum gastrin determinations as determined by radioimmunoassay.

Topics: Diagnostic Errors; Endoscopy, Gastrointestinal; Gastrins; Humans; Hyperlipidemias; Male; Middle Aged; Zollinger-Ellison Syndrome

Processing-independent radioimmunoanalysis for progastrin showed that extracts of normal pancreatic tissue from normal subjects (n = 5) and from patients with adenocarcinoma of the papilla of Vater (n = 4) contain progastrin and its products. The concentrations varied from 0.1 to 5.8 pmol/g tissue, of which carboxyamidated bioactive gastrins constituted 0.03-1.9 pmol/g. In histologically normal and nonneoplastic pancreatic tissue from patients with duodenal (n = 3) and pancreatic (n = 2) gastrinomas the expression of gastrin was significantly higher-14.5 pmol/g (median), of which 28% was bioactive amidated gastrins. Gastrin-17 was the main bioactive product, but its immediate precursor, glycine-extended gastrin-17, constituted the predominant part of the preprogastrin product in pancreatic tissue. Proper gastrinoma tissue contained several precursor forms, including intact unprocessed progastrin. Progastrins were also found in high concentrations in plasma from the gastrinoma patients. The results raise the possibility that increased expression of progastrin and its products in non-neoplastic pancreatic tissue is a primary defect predisposing to neoplasia.

Topics: Adenocarcinoma; Ampulla of Vater; Common Bile Duct Neoplasms; Gastrinoma; Gastrins; Gene Expression; Humans; Pancreas; Pancreatic Neoplasms; Protein Precursors; Protein Processing, Post-Translational; Zollinger-Ellison Syndrome

Topics: Administration, Oral; Biopsy; Child, Preschool; Endoscopy, Gastrointestinal; Female; Gastrins; Humans; Infusions, Intravenous; Omeprazole; Pepsinogens; Peptic Ulcer; Pyloric Antrum; Zollinger-Ellison Syndrome

The authors demonstrate three patients--two with a nesidioma of the B-cells with insulin production, the third had a nesidioma made up of non-B cells with clinical manifestations of gastrin hypersecretion. The surgical solution was successful in the patients with B-cell nesiodiomas.

Topics: Adolescent; Adult; Epilepsy; Female; Gastrins; Humans; Insulin; Insulin Secretion; Insulinoma; Male; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Antisera were raised against fragment 38-54 of human progastrin. All of eight immunized rabbits responded, but only one (No. 2145) produced high-titer (3.2 x 10(4)) and high-avidity (Keff degrees = 1.2 x 10(12) l/mol) antibodies. A radioimmunoassay based on antiserum 2145 and monoiodinated gastrin-34 was specific for the N-terminal sequence of human gastrin-34. It measured concentrations of 9.7 +/- 1, 18.4 +/- 2 pmol/l (mean +/- SEM) and 1.553 (0.7-476) nmol/l (median (range], respectively, in sera from normal subjects (n = 20), patients with duodenal ulcer (n = 19), and Zollinger-Ellison patients (n = 8). Conventionally measured concentrations of carboxyamidated gastrins in the same sera were 21.4 +/- 1, 23.8 +/- 3 pmol/l (mean +/- SEM) and 0.833 (0.4-214) nmol/l (median (range)), respectively. The results show that radioimmunoassays specific for the N-terminus of human gastrin-34 discriminate between healthy subjects and patients with duodenal ulcer. The improved diagnostic specificity is due to co-measurement of unprocessed and partly processed progastrins that occur in plasma of patients with duodenal ulcer disease and gastrinomas. We suggest that conventional gastrin assays are supplemented with assays specific for the N-terminus of gastrin-34 in studies of duodenal ulcer disease.

Topics: Amino Acid Sequence; Anemia, Pernicious; Animals; Chromatography, Gel; Duodenal Ulcer; Gastrins; Immune Sera; Molecular Sequence Data; Protein Precursors; Rabbits; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Bombesin; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

A Zollinger-Ellison syndrome due to an ovarian mucinous cystadenoma of borderline malignancy is reported in a 76-year-old woman. Immunostaining procedures showed reactivity for gastrin in neoplastic cells. After operation, the patient has remained without symptoms for 6 years. This is the fifth case reported in the literature. All of these ovarian tumors were considered mucinous cystadenomas histologically.

Topics: Aged; Cystadenoma; Female; Gastrins; Hormones, Ectopic; Humans; Ovarian Neoplasms; Zollinger-Ellison Syndrome

The metabolism of histamine in the human gastric mucosa was studied in the basal state and during pentagastrin stimulation. Studies were made in healthy volunteers and in patients with peptic ulcer disease. Mucosal biopsies were taken from antral and oxyntic gland areas whereupon histamine content, histidine decarboxylase activity, and histamine methyltransferase activity were simultaneously assayed. Histamine content of the oxyntic gland mucosa was decreased as a consequence of pentagastrin administration in all groups studied, and this decrease was numerically largest in patients with duodenal ulcer disease. Pentagastrin induced a significant increase in histidine decarboxylase activity of the oxyntic gland mucosa with the most profound increase seen in patients with duodenal ulcer. The highest rates of histamine formation were present in the oxyntic mucosa of patients with Zollinger-Ellison syndrome. The activity of histamine methyltransferase was the same in all groups studied and was not changed by pentagastrin. In conclusion, pentagastrin administration in humans is followed by a significant mobilization of histamine only from the oxyntic gland mucosa, an effect that is more pronounced in patients with duodenal ulcer disease.

Topics: Adult; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Histamine; Histamine N-Methyltransferase; Histidine Decarboxylase; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pentagastrin; Stimulation, Chemical; Stomach Ulcer; Zollinger-Ellison Syndrome

Progastrin and all of its processing products were measured in serum from 48 patients with Zollinger-Ellison syndrome, 42 patients with duodenal ulcers, and 34 normal subjects. A processing-independent gastrin analysis and a conventional radioimmunoassay for the biologically active alpha-amidated gastrins were used. In serum from normal subjects, 87% (median; range, 27%-160%) of all progastrin products were alpha-amidated gastrins, whereas they constituted only 39% (15%-130%) in serum from patients with duodenal ulcers (p less than 0.01) and 46% (16%-100%) in serum from gastrinoma patients (p less than 0.01). A significantly lower percentage of alpha-amidated gastrin was found in patients with hepatic metastases (23%) than in patients with apparently benign tumors (54%). Chromatography of serum showed that large progastrin molecules occurred mainly in patients with malignant tumors, whereas smaller glycine-extended precursors dominated in patients with benign tumors. The results indicate that the total progastrin product reflects tumor synthesis of gastrin better than conventional measurements of alpha-amidated gastrin. Moreover, the results suggest that a low degree of processing of progastrin could serve as a predictor of a malignant clinical course at an early stage of the disease.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Chromatography, Gel; Duodenal Ulcer; Female; Follow-Up Studies; Gastrins; Humans; Male; Middle Aged; Protein Precursors; Radioimmunoassay; Zollinger-Ellison Syndrome

The endocrine cells of the oxyntic mucosa of five patients with longstanding Zollinger-Ellison syndrome were quantitatively investigated with electron microscopy and two light microscopic methods (Grimelius and immunostaining for chromogranin A). Ultrastructurally, the volume density of endocrine cells was 3.2% +/- 1.1% of the mucosal epithelial component, a 168% increase (P less than 0.001) over the value found in normal subjects. Of the six endocrine cell types of human oxyntic mucosa, only enterochromaffinlike cells increased in cell density (65% +/- 15% of the total endocrine cell mass), size, and number of cell profiles per unit area. The enterochromaffinlike cells also underwent morphological changes of secretory granules with a decrease in vacuolated forms, increase in elongated profiles, and appearance of granules with a punctate structure of the core. The latter variety of granules was previously observed only in carcinoid tumors of the oxyntic mucosa and is possibly related to the enterochromaffinlike cell hyperplasia-neoplasia sequence seen in hypergastrinemic patients. A positive relationship was found between endocrine cell densities evaluated ultrastructurally and with chromogranin A immunostaining. It is concluded that in Zollinger-Ellison syndrome, the trophic effects induced by longstanding hypergastrinemia are strictly selective for enterochromaffinlike cells and are associated with ultrastructural features typical for enterochromaffinlike cell tumors.

Topics: Adult; Chromogranins; Cytoplasmic Granules; Enterochromaffin Cells; Female; Gastrins; Humans; Immunohistochemistry; Male; Microscopy; Microscopy, Electron; Middle Aged; Parietal Cells, Gastric; Vacuoles; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome in a 76-year-old woman is reported. The source of the hypergastrinemia proved to be an ovarian cystadenocarcinoma. Resection was performed and the diagnosis was confirmed histologically, immunohistochemically and by determination of gastrin in tumor tissue and in serum. The long-term result was good.

Topics: Aged; Cystadenocarcinoma; Female; Gastrins; Hormones, Ectopic; Humans; Ovarian Neoplasms; Zollinger-Ellison Syndrome

A case of malignant gastrinoma of the jejunum and jejunal mesentery, with findings of metastasis in the liver was studied. Tumor resection and remnant gastrectomy, as well as liver biopsy, were performed. Of all the tumors removed, the metastatic tumor had the lowest gastrin content, which was 1.5 times that found in normal human antral mucosa. The gastrin distribution was of four peaks and one peak for the main tumor, versus two peaks for the metastatic tumor in which G17 was the main component. Seven years after the operation, computed tomography (CT) scan indicated there was stabilization of the liver metastasis, and now, ten years after the total gastrectomy, the patient is well and working full-time. Such an analysis can be of value in determining the prognosis in cases of malignant gastrinoma with liver metastasis.

Topics: Adult; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Jejunal Neoplasms; Liver Neoplasms; Male; Time Factors; Zollinger-Ellison Syndrome

Topics: Anemia, Aplastic; Calcium; Gastrins; Humans; Hyperparathyroidism; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

7 gastrinomes and 1 gastrin-producer complex carcinoma-carcinoid tumor were examined by light and electron microscopical-method and by immunohistochemical method. In six cases, the tumor was in the pancreas or in the wall of duodenum; in two cases its localisation was of extra-gastroenteropancreatic (liver, lymph node). All patients developed Zollinger-Ellison syndrome, three patients bled and one had diarrhea. One patient had other tumors, besides gastrinome, which were characteristic of MEN-I syndrome. By immunohistochemical methods all tumors proved to be gastrin and neuron-specific-enolase positive. In four cases somatostatin positivity, in some cases glucagon, pancreatic polypeptide, S-100 protein, keratin and carcinoembryonal antigen positivity were detected. Relation could not be detected between other polypeptide hormones, produced besides gastrin, and biological behaviour of tumor and clinical symptoms.

Topics: Carcinoid Tumor; Carcinoma; Duodenal Neoplasms; Gastrins; Humans; Pancreatic Neoplasms; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Fasting; Gastric Acid; Gastrinoma; Gastrins; Humans; Zollinger-Ellison Syndrome

The clinical, microscopic, immunohistochemical and ultrastructural features of 7 gastrinomas and 1 combined carcinoma-carcinoid tumor were evaluated. The tumors were located in the pancreas or duodenal wall in 6 cases, and on extragastro-enteropancreatic sites in 2 (liver or peripancreatic lymph node). All patients had the Zollinger-Ellison syndrome, 3 of them with additional bleeding and 1 with diarrhea. One patient with gastrinoma had additional tumors characteristic of the MEN-I syndrome. Immunohistochemistry showed gastrin and neuron-specific enolase-positivity in all of the tumors. Somatostatin was found in 4 cases, and single cell glucagon, pancreatic polypeptide. S-100 protein, keratin as well as carcino-embryonic antigen positivity in another few. Additional hormone production did not appear to be connected with biological behaviour of the tumors or with the clinical symptoms.

Topics: Adolescent; Adult; Aged; Carcinoembryonic Antigen; Carcinoid Tumor; Duodenal Neoplasms; Female; Gastrins; Glucagon; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Phosphopyruvate Hydratase; S100 Proteins; Somatostatin; Zollinger-Ellison Syndrome

A 43 year old man is presented who suffered from the association of a toxic adenoma of the thyroid gland and a Zollinger-Ellison syndrome (ZES) due to a metastasizing duodenal gastrinoma. There were no other signs of a multiple endocrine neoplasia syndrome, type I (MEN-I). The patient presented here shows that the association of ZES and thyroid disease may also occur in patients with sporadic ZES.

Topics: Adenoma; Adult; Duodenal Neoplasms; Gastrectomy; Gastrinoma; Gastrins; Humans; Hyperthyroidism; Immunohistochemistry; Male; Thyroid Neoplasms; Zollinger-Ellison Syndrome

A case of Zollinger-Ellison syndromes in a fifty year-old male that was successfully treated with a H+-K+ ATPase inhibitor (Omeprazol) is reported. The patient underwent a partial gastrectomy in 1984, but had been suffering from multiple refractory stomal and jejunal ulcers after the operation. In 1987, hypergastrinemia (760 pg/ml) was detected, and the presence of gastrinomas in the pancreatic head accompanied by a multiple liver metastasis was subsequently confirmed by CT-angiography and by the gastrin level detected in percutaneous, transhepatic, portal venous samples. A secretin provocation test proved to be negative, and the ulcers resisted the H2-receptor antagonists, but the patient was successfully cured shortly after the administration of an H+-K+ ATPase inhibitor.

Topics: Adenosine Triphosphatases; Gastrinoma; Gastrins; H(+)-K(+)-Exchanging ATPase; Humans; Male; Middle Aged; Omeprazole; Pancreatic Neoplasms; Secretin; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Prealbumin, one of the main thyroxine transport proteins, has recently been shown to be a valuable immunohistochemical marker of neuroendocrine tumours. We report the case of a multisecretory pancreatic endocrine tumour whose prealbumin secretion was so high that it produced a peak on routine serum protein electrophoresis and induced a euthyroid hyperthyroxinemia. The maximal binding capacity of prealbumin for thyroxine was indeed markedly increased, whereas its affinity for this hormone was normal. The tumour was associated with gastric hyperacidity and hypergastrinemia thereby evoking a Zollinger-Ellison syndrome. The secretin stimulation test and gastrin tumoural immunohistochemistry were, however, negative. We suggest that the concomitant tumoural production of gastrin-releasing peptide was responsible for the gastric hyperacidity and hypergastrinemia. This hormone probably also accounted for a moderate hypercorticism.

Topics: Adrenocortical Hyperfunction; Gastrins; Humans; Hyperthyroxinemia; Immunoenzyme Techniques; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Prealbumin; Thyroxine-Binding Proteins; Zollinger-Ellison Syndrome

In patients with Zollinger-Ellison syndrome, serum gastrin level is increased by secretin and is decreased by somatostatin. To elucidate the cellular mechanism for these actions, we investigated the direct effects of secretin and somatostatin on dispersed gastrinoma cells from a patient with Zollinger-Ellison syndrome. In the presence of 3-isobutyl-1-methylxanthine, secretin significantly stimulated gastrin release from dispersed gastrinoma cells, which was inhibited by somatostatin. In the presence of guanosine 5'-triphosphate, furthermore, secretin enhanced adenylate cyclase activation in the membranes from these cells, and this activation was reduced by somatostatin, whereas neither secretin nor somatostatin affected inositol phospholipid turnover. On the other hand, removal of guanosine 5'-triphosphate from incubation medium abolished both the stimulatory effect of secretin and the inhibitory effect of somatostatin on adenylate cyclase activation. Furthermore, pertussis toxin pretreatment reversed the ability of somatostatin to inhibit secretin-induced increase in gastrin release and activation of adenylate cyclase. Thus, in this gastrinoma patient, secretin and somatostatin appeared to act directly on gastrinoma cells to stimulate and inhibit gastrin secretion, respectively, by modulating adenylate cyclase activation, probably via guanine nucleotide-binding proteins.

Topics: Adenylyl Cyclases; Female; Gastrins; Guanosine Triphosphate; Humans; In Vitro Techniques; Inositol Phosphates; Middle Aged; Secretin; Somatostatin; Zollinger-Ellison Syndrome

To evaluate criteria of positivity for and usefulness of both the secretin and calcium gastrin-provocative tests in patients with the Zollinger-Ellison syndrome.. Prospective trial in consecutive patients.. Referrals to a clinical research center.. Consecutive sample of 80 patients with the Zollinger-Ellison syndrome.. Kabi-secretin (2 U/kg body weight) given by intravenous bolus and calcium gluconate (10%) (54 mg/kg.h [5 mg/kg.h of calcium]) given by continuous intravenous infusion for 3 hours. Serum gastrin measured at -15, and -1 minutes before, and 2, 5, 10, 15, 20, and 30 minutes after secretin, or every 30 minutes for 3 hours during the calcium infusion. Serum calcium and serum gastrin were measured simultaneously during the calcium infusion.. There was no significant difference in the responses of patients with different extents or locations of the tumor, presence or absence of multiple endocrine neoplasia, type-I, or with fasting gastrin less than or greater than 1000 pg/mL. In patients with fasting gastrin of less than 1000 pg/mL, the sensitivity of the secretin test using the criterion of an increase in gastrin of at least 110 pg/mL was 93% (CI, 76% to 99%) and for an increase of 200 pg/mL it was 85% (CI, 66% to 96%), (P greater than 0.05). With the calcium infusion test, the sensitivity using the criterion of an increase of 395 pg/mL was 43%, (CI, 23% to 66%) and for an increase of 50% was 74% (CI, 52% to 90%), (P less than 0.01). The calcium infusion test was positive in 33% of patients with a negative secretin test. With the secretin test, 75% of patients had a positive response by 5 minutes, 95% by 10 minutes, 100% by 15 minutes, and 6% only at 2 minutes. With calcium infusion, patients had positive responses at 120 to 180 minutes.. The secretin test is preferred over the calcium test because of its greater sensitivity and simplicity. The recommended criteria are a 200 pg/mL increase for the secretin test and a 395 pg/mL increase for the calcium test. The calcium test should be reserved for patients having a negative secretin test, gastric acid hypersecretion, and a strong clinical suspicion of the Zollinger-Ellison syndrome.

Topics: Adolescent; Adult; Aged; Calcium; Chi-Square Distribution; Confidence Intervals; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Prospective Studies; Secretin; Sensitivity and Specificity; Time Factors; Zollinger-Ellison Syndrome

The purpose of this work was to evaluate the proposed usefulness of a standard meal-stimulated gastrin provocative test in: (1) distinguishing Zollinger-Ellison syndrome (ZES) from antral syndromes; (2) localizing duodenal gastrinomas; or (3) suggesting that patients with multiple endocrine neoplasia type I (MEN-I) may have an increased incidence of antral syndromes.. Seventy-four consecutive patients with ZES referred to the National Institutes of Health were studied prospectively. The extent and location of gastrinomas, acid secretory studies, and the presence or absence of MEN-I were determined and correlated with the results of the gastrin response to standard meal provocative testing.. For patients with fasting serum gastrin levels less than 1,000 pg/mL (n = 43), only 44% had a less than 50% increase over the pre-meal value, which is reported to be the typical response in ZES, and 40% had a 50% to 99% increase. Furthermore 16% had a 100% or greater increase, 9% a 150% or greater increase, and 5% a 200% or greater increase, which overlaps with values reported to be characteristic of 98%, 92%, and 46% of patients with antral syndromes. Results did not differ for patients with or without MEN-I, depend on the extent of the gastrinoma (duodenal versus pancreatic gastrinomas), the presence of previous gastric surgery or type of gastric surgery, or for patients with fasting serum gastrin concentrations greater than or equal to 1,000 pg/mL or less than 1,000 pg/mL. studies of four patients before and after resection of the gastrinoma, who prior to surgery had a greater than 100% increase in gastrin secretion after the meal, demonstrated that all patients had a less than 100% increase postoperatively even though no gastric resection was done.. Approximately half of the patients with ZES have a greater than 50% increase in serum gastrin concentration following a standard test meal and one fifth have a 100% or greater increase. Therefore, they cannot be distinguished on this basis from patients with antral syndromes. The increased serum gastrin level after the meal in these patients with ZES appears to be due to the gastrinoma. Furthermore, the current study provides no evidence for the proposals that antral syndromes are more common in patients with MEN-I, that gastric surgery affects the meal response in patients with gastrinomas, or that the meal test is useful in localizing duodenal gastrinomas.

Topics: Adolescent; Adult; Aged; Duodenal Neoplasms; Eating; Female; Gastric Acid; Gastrinoma; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Prospective Studies; Zollinger-Ellison Syndrome

We have followed 14 patients with the Zollinger-Ellison syndrome for a median period of 9 years. All patients have suffered from peptic ulcer disease and six of the 14 have had complications such as bleeding or perforated ulcer. Almost half the patients have had diarrhoea as a dominant symptom and 4 patients suffered from multiple endocrine neoplasia. Before 1978, the year when the H2-receptor antagonists were introduced, the majority of the patients were operated with total gastrectomy. After that year there has been no need for gastrectomies, but all but two patients have undergone an explorative laparotomy. We have been able to localize the gastrinoma in 9 of 12 operated patients; in 7 cases it was localized within the gastrinoma triangle. Three of the patients are considered to have been cured after surgery. Eight patients have needed adjuvant acid-reducing medical therapy. Five of these have been failures to high doses of H2-receptor antagonists and have been successfully treated with omeprazole. Five patients have died during the follow-up period and death in two of these cases was related to tumor progression.

Topics: Aged; Female; Follow-Up Studies; Gastrinoma; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Omeprazole; Zollinger-Ellison Syndrome

In the Zollinger-Ellison syndrome, symptoms and complications are due to hypersecretion of acid, and the first therapeutic step is to suppress the acid secretion. Long-term treatment with histamine H2-receptor antagonists was compared with omeprazole treatment. A total of 30 consecutive ZES patients were treated continuously with H2-receptor antagonists. During long-term treatment, a marked tachyphylaxis was noted, more than 50% of the patients had periods of dyspepsia, recurrent ulcers were found in 10 patients and in 16 a decline in the action of the H2-receptor antagonist required a change to omeprazole after a median duration of 36 months. A total of 22 patients were treated with omeprazole. During long-term treatment, the dose could be reduced slightly. Inhibition of acid secretion was maintained in all cases, and none had dyspeptic symptoms. The median duration of treatment was 18 months, with a range of 1-120 months (H2-receptor antagonists) and 27 months with a range of 1-66 months (omeprazole). No side-effects were seen with omeprazole.

Topics: Adult; Aged; Cimetidine; Female; Gastric Acid; Gastrins; Humans; Long-Term Care; Male; Middle Aged; Multiple Endocrine Neoplasia; Omeprazole; Ranitidine; Zollinger-Ellison Syndrome

The frequent occurrence of cholelithiasis noted in the follow-up of patients who underwent total gastrectomy because of Zollinger-Ellison syndrome prompted us to study this phenomenon. Cholelithiasis is known to be more common after truncal vagotomy, with or without concomitant subtotal gastric resection, and the prevalence of gallstones in these patients is reported to be 16% to 38%. To date, however, no long-term study has investigated the prevalence of gallstones after total gastrectomy in patients with the Zollinger-Ellison syndrome. Since 1961, 26 patients with the Zollinger-Ellison syndrome have undergone total gastrectomy and were enrolled in a Medical College of Wisconsin Clinical Research Center protocol that allowed follow-up to assess the development of cholelithiasis. Eight patients had cholecystectomy at the time of total gastrectomy (seven patients had stones), leaving 18 patients with a normal gallbladder and no gallstones at the time of total gastrectomy. Four patients died early, two of surgical complications, one of tumor progression, and one of alcohol-related trauma. During follow-up, cholelithiasis has developed in 10 of 14 patients (71%) at risk; the mean time to gallstones was 6.3 years (range, 1.2 to 12.9 years). The predictable occurrence of cholelithiasis after total gastrectomy in patients with the Zollinger-Ellison syndrome suggests that cholecystectomy should be performed at the time of total gastrectomy.

Topics: Adult; Aged; Child; Cholelithiasis; Female; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Male; Middle Aged; Vagotomy; Zollinger-Ellison Syndrome

A 59-year-old female presented with multifocal peptic ulcer disease and diarrhea. A fasting serum gastrin level obtained while the patient was receiving no antacid therapy was normal. A secretin stimulation test was positive. A small gastrinoma was found in the anterior duodenal wall at exploratory laparotomy. Normal fasting gastrin levels do occur in patients with overt Zollinger-Ellison syndrome and should not deter further investigation if clinical suspicion of this syndrome is high.

Topics: Duodenal Neoplasms; Female; Gastrinoma; Gastrins; Humans; Middle Aged; Zollinger-Ellison Syndrome

A case of Zollinger-Ellison due to hyperplasia of antral gastrin cells in a 11 year-old child is reported. Only 49 cases of this syndrome in children have been published. The diagnosis (gastrin stimulation test, immunohistochemical detection of endocrine cells and therapeutic strategy are outlined).

Topics: Child; Female; Gastrins; Humans; Hyperplasia; Pyloric Antrum; Zollinger-Ellison Syndrome

The prevalence of peptic ulcer disease was retrospectively analysed in 35 patients affected by primary hyperparathyroidism consecutively observed from 1977 through 1987. Eight of the examined patients (22.8%) had peptic ulcer (7 duodenal and 1 gastric ulcer), that in five cases (14%) represented the first clinical manifestation of the endocrine disease. A Zollinger-Ellison syndrome was demonstrated in three cases (8.5% of the total series, 37% of the patients with ulcer). There was no difference in calcium, gastrin and parathormone serum level between patients with and without ulcer, excluding patients with Zollinger-Ellison syndrome. These data confirm the high prevalence of peptic ulcer disease in hyperparathyroidism, but the mechanism causing this association remains to be elucidated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcium; Female; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Hormone; Peptic Ulcer; Retrospective Studies; Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome is usually caused by a gastrin-secreting tumor in or near the pancreas. We describe a patient in whom an ovarian cystadenocarcinoma was the cause of the syndrome. The patient presented with a short history of peptic ulceration and development of a large pelvic mass. Investigations demonstrated a basal acid output of 37.8 mEq/h and a maximal acid output of 36.0 mEq/h, and the plasma concentration of gastrin was 830 pg/ml (normal less than 100). Secretin and calcium infusion tests were positive, and a meal test was compatible with Zollinger-Ellison syndrome. Imaging studies demonstrated a normal liver and pancreas but a large cystic right ovarian mass. Resection of the mass resulted in a marked reduction in gastric acid output, a fall in plasma gastrin concentration to normal, negative calcium and secretin tests, and a normal (positive) meal test. Histology of the mass showed it to be a mucinous cystadenocarcinoma. The tumor stained with immunoperoxidase technique was positive for gastrin, and the cyst fluid contained high concentrations of gastrin and calcitonin. One year later, the patient has no biochemical or imaging evidence of tumor. Ovarian, gastrin-producing tumors and pancreatic gastrinomas cannot be distinguished by provocative tests, and negative imaging studies do not exclude a pancreatic tumor. Patients with an ovarian mass and Zollinger-Ellison syndrome should have a bilateral oophorectomy and a careful exploration of the pancreatic area.

Topics: Cystadenocarcinoma; Female; Gastric Acid; Gastrins; Humans; Immunoenzyme Techniques; Middle Aged; Ovarian Neoplasms; Ovary; Zollinger-Ellison Syndrome

A computer simulation model is presented of the gastric phase regulation of gastric acid secretion in humans. The model is based on experimental data from the literature and includes terms representing gastric pH and gastric volume-dependent gastrin secretion, gastrin-dependent acid secretion, food storage in the stomach, and gastric emptying. We have explored the predictive value of the model in assessing the relative importance of gastric pH-dependent and gastric volume-dependent acid secretion mechanisms under various conditions. Similarly we have studied the role of gastric acid deregulation in achlorhydria, the Zollinger-Ellison syndrome, and duodenal ulcer, and the influence of the antacid drugs cimetidine and ranitidine under duodenal ulcer conditions. Model analysis of normal gastric acid regulation suggests that gastric volume-controlled acid secretion is of major importance during eating and predicts that pH-dependent gastrin secretion is of major importance in preventing excessively low pH levels between meals and during the night.

Topics: Achlorhydria; Cimetidine; Computer Simulation; Duodenal Ulcer; Food; Gastric Acid; Gastric Emptying; Gastrins; Humans; Hydrogen-Ion Concentration; Mathematics; Models, Biological; Ranitidine; Stomach; Zollinger-Ellison Syndrome

The long-acting somatostatin (SMS) analog, SMS 201-995 has beneficial effects on APUDomas. In two Zollinger-Ellison syndrome (ZES) patients we assessed basal acid output (BAO) and 24-h pH under SMS and compared them to controls. We also assessed total gastrin, gastrin 17, insulin, glucagon, C-peptide, and SMS by radioimmunoassay. In the benign gastrinoma, an acid-controlling action of SMS was shown, elevating the 24-h pH threshold over the pH range 1.5-5 of 55-10% compared with control. A parallel inhibition of the gastrins greater than 90% was apparent. We found no beneficial effect on gastric acid secretion and on tumor gastrin in the malignant gastrinoma despite a fourfold higher plasma SMS level. Non-tumor-related peptides were suppressed by approximately 50% and in contrast to gastrin they again reached pre-SMS levels before the next dose of the drug. We conclude that SMS is more effective in benign than in malignant gastrinomas, and may be exclusively so.

Topics: Female; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Octreotide; Zollinger-Ellison Syndrome

Among 30 patients with islet cell neoplasms or hyperplasia who exhibited marked gastric acid hypersecretion and peptic ulceration and/or diarrhea, fasting plasma gastrin concentrations were less than 150 pg/ml in 11 patients, whereas the remaining 19 patients had hypergastrinemia. Plasma extracts from seven of these 11 patients were assayed for acid secretagogue activity in rats. All seven plasma extracts had secretagogue activity that was not found in the plasma extracts of ten patients with ordinary duodenal ulcer disease. Each of the tumor or pancreatic tissue extracts obtained from nine patients exhibited secretagogue activity in rats even though tissue gastrin content was 101.9 pmol (213.8 ng).g-1 or less. The secretagogue activity of the tumor extracts was confirmed in conscious gastric fistula dogs. The tumors' secretagogue activity, in contrast to gastrin, was destroyed by trypsin. It was eluted between porcine motilin and human gastrin I from a Sephadex G-50 (Pharmacia LKB Biotechnology, Inc., Piscataway, NJ) superfine column and was not retained by CM-cellulose, at pH 8.5. Its retention time during reverse phase HPLC on a C18 column also differed from those of G17 and G34. Thus, this secretagogue activity appeared mediated by a small, acidic peptide with a molecular size of about 2000 to 3000 daltons. The present study indicates that plasma and tumor extracts of these 11 patients contain a gastric acid secretagogue activity mediated by a nongastrin peptide. We suggest that what may be a distinct clinical entity associated with endocrine neoplasms of the pancreas should be considered in the face of excessive acid hypersecretion without fasting hypergastrinemia.

Topics: Adult; Aged; Animals; Biological Assay; Dogs; Eating; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Rats; Rats, Inbred Strains; Secretin; Tissue Extracts; Trypsin; Zollinger-Ellison Syndrome

We report a 45-year-old woman with chronic peptic ulcer disease and multiple episodes of bowel obstruction, who was admitted with gastric outlet obstruction. Because of gastric hypersecretion, a diagnosis of Zollinger-Ellison syndrome was suspected and an initial serum gastrin of 1,251 pg/ml supported this diagnosis. Subsequent evaluation failed to reveal a gastrinoma. A repeat serum gastrin level after 14 days of continuous nasogastric decompression was 43 pg/ml, suggesting that the initial hypergastrinemia was due to antral distention. It is important to consider the possibility of gastric outlet obstruction as a stimulus for serum gastrins in the range previously considered diagnostic for the Zollinger-Ellison syndrome.

Topics: Diagnosis, Differential; Female; Gastric Dilatation; Gastrins; Humans; Intestinal Obstruction; Middle Aged; Peptic Ulcer; Pyloric Antrum; Zollinger-Ellison Syndrome

Topics: Calcium; Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

Serum gastrin and gastric endocrine cell numerical densities were examined in 22 patients with long-standing Zollinger-Ellison syndrome who were receiving either ranitidine, omeprazole, or other antisecretory drugs (SMS 201-995 or pirenzepine with or without ranitidine) for long periods of time. Fifteen patients had iterative biopsies. Twenty-one subjects with normal endoscopy, serum gastrin, and acid secretion served as controls. Individual fundic argyrophil cell density was above the highest control value in 77% of the patients, whatever the treatment. Argyrophil cell densities tended to be higher in women than in men. During the survey, fundic carcinoids developed in one ranitidine- and in one omeprazole-treated patient. Fundic argyrophil cell densities were correlated with serum gastrin levels (r' = 0.730, p less than 0.001). Antral somatostatin cell density was not modified in any patients as compared with controls, nor was antral gastrin cell density except in omeprazole-treated patients. In these patients, gastrin cell density and gastrin to somatostatin cell ratio were significantly higher than in all other patients or controls. Such increases may indicate true gastrin cell hyperplasia in relation to drug-induced profound acid inhibition.

Topics: Adult; Aged; Anti-Ulcer Agents; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Octreotide; Sex Factors; Zollinger-Ellison Syndrome

Gastrinomas are now being detected at an earlier stage than was formerly the case. Furthermore, with the ability to control acid secretion, emphasis has been placed on identifying gastrinoma patients who are potentially curable by tumor resection rather than by palliative gastrectomy. Despites estimates suggesting that 20-40% of sporadic gastrinoma patients can be successfully resected for cure, as many as 40% of such patients have occult tumors that elude detection. In an effort to better localize gastrinomas, we have used percutaneous transhepatic venous (THVS) gastrin sampling over the past 10 years. From 1978 to 1988, THVS was used in 46 patients in whom there was no other evidence of metastatic gastrinoma by conventional studies. Gastrinomas were found at operation in all but one patient. The purpose of this report is to emphasize that occult tumors are most often found in the duodenal wall, and frequently they may be no greater than 2 mm in diameter. Five recent cases illustrate that these small tumors or microgastrinomas may be the sole source of hypergastrinemia and can be cured by local excision. These recent cases emphasize that microgastrinomas are not usually palpable through the duodenal wall. They may be detected only after duodenotomy and meticulous evaluation of the mucosa by eversion and direct palpation. Duodenotomy and intraluminal exploration should be considered an essential component of the operation for patients with extrapancreatic gastrinomas.

Topics: Aged; Duodenal Neoplasms; Duodenum; Female; Gastrinoma; Gastrins; Humans; Intestinal Mucosa; Male; Middle Aged; Zollinger-Ellison Syndrome

Over a five-year period, we measured concentrations of gut hormones in plasma samples from 353 patients in whom diagnoses of pancreatic endocrine tumors were subsequently confirmed. A median of 19 months (range, 7 to 120) after the initial diagnosis, 24 of these patients (6.8 percent) had elevated concentrations of other hormones in association with new clinical symptoms. In 13 of these patients (8 with glucagonomas, 3 with tumors secreting vasoactive intestinal polypeptide, and 2 with insulinomas), hypergastrinemia developed along with the clinical features of a gastrinoma; 5 patients died of gastrointestinal perforation or bleeding, apparently caused by this second tumor. We conclude that patients with pancreatic endocrine tumors, regardless of their initial clinical picture, require continued surveillance for new elevations of hormones.

Topics: Adenoma, Islet Cell; Adult; Aged; Gastrins; Gastrointestinal Hemorrhage; Glucagon; Glucagonoma; Hormones; Humans; Insulinoma; Middle Aged; Pancreatic Neoplasms; Time Factors; Vasoactive Intestinal Peptide; Vipoma; Zollinger-Ellison Syndrome

Five patients with Zollinger-Ellison syndrome (ZES) have been treated during 9-12 months with long-acting somatostatin (SMS 201-995). Basal acid output presented a sustained decrease in 4 of 5 cases, below 10 mmol/h in three patients, allowing ranitidine discontinuation. No escape phenomenon was observed. Maximal acid secretion progressively decreased, suggesting an SMS antitrophic effect. Serum gastrin level was affected in a greater extent, showing a mean 87% decrease throughout the treatment period. Thus three patients kept normal serum gastrin levels in the long-term; one escaped to SMS after 9 months. Associated endocrine neoplasia were poorly influenced by SMS. No convincing evidence of tumor size variation was noted. Tolerance of SMS was excellent in the five patients. SMS' antitrophic and antigastrin properties could be of great interest in long-term management of ZES.

Topics: Adult; Antineoplastic Agents; Drug Tolerance; Endocrine System Diseases; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Octreotide; Ranitidine; Secretin; Somatostatin; Time Factors; Zollinger-Ellison Syndrome

Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adult; Cells, Cultured; Chromaffin System; Colforsin; Enterochromaffin Cells; Female; Gastrins; Humans; Immunohistochemistry; Liver Neoplasms; Phorbol Esters; Radioimmunoassay; Secretin; Somatostatin; Tetradecanoylphorbol Acetate; Zollinger-Ellison Syndrome

An increased serum pepsinogen I (PG I) concentration has been reported to be a marker of inherited peptic ulcer disease. Since both the Zollinger-Ellison syndrome and hyperparathyroidism, components of the familial multiple endocrine neoplasia type I syndrome (MEN I), are often associated with peptic ulcer, we have studied serum PG I concentrations in members of six well-defined families with MEN I. Serum PG I concentrations in 20 family members with hyperparathyroidism ranged from 35 to 864 ng/ml compared to 21-92 ng/ml in 16 nonaffected MEN I members. However, serum PG I levels were significantly higher (P less than 0.01) in the hyperparathyroid patients with hypergastrinemia (PGI median 192, range 75-864 ng/ml) than in those with normogastrinemia (PGI median 75, range 35-139 ng/ml). In fact, five of seven patients with hyperparathyroidism and hypergastrinemia compared to only one of 13 hyperparathyroid patients without hypergastrinemia had increased serum PG I levels above 130 ng/ml. We conclude that in the MEN I syndrome, increased serum PG I levels are found in patients with Zollinger-Ellison syndrome but not in hyperparathyroid patients with normogastrinemia and not in nonaffected MEN I members. The results indicate that in familial MEN I, hyperpepsinogenemia I is not inherited as a genetic trait but suggest that the elevated serum PG I levels are secondary to chronic hypergastrinemia.

Topics: Female; Gastrins; Humans; Hypercalcemia; Hyperparathyroidism; Male; Multiple Endocrine Neoplasia; Pedigree; Pepsinogens; Zollinger-Ellison Syndrome

Fifty-five consecutive patients with Zollinger-Ellison syndrome who underwent exploratory laparotomies for gastrinoma resection were evaluated prospectively to determine the effect of gastrinoma resection on acid secretion and to establish criteria for safe and effective perioperative management of gastric acid hypersecretion. In 15 patients (27%) no tumor was found and postoperative serum gastrin, basal acid output (BAO), and maximal acid output (MAO) were unchanged. Twenty-one patients (38%) had gastrinomas resected and were biochemically cured. Median fasting gastrin, median delta secretin, mean BAO, and mean MAO decreased 89%, 94%, 80%, and 43%, respectively, at 3-month follow-up in these patients. In 19 patients gastrinomas were resected, but patients were not cured, and median fasting gastrin, median delta secretin, mean BAO, and mean MAO decreased 47%, 10%, 26%, and 25%, respectively. Forty percent of patients with gastrinoma resected and cured and 81% of patients with gastrinoma resected but not cured continued to hypersecrete acid (BAO greater than 10 mEq/hr) at 3- to 6-month follow-up. Acid control was managed perioperatively during gastrinoma resection by continuous intravenous infusion of H2 receptor antagonists at a dose established by preoperative titration to decrease acid output to less than 10 mEq/hr. Thirty patients were treated with cimetidine at a mean dose of 3.2 mg/kg/hr for a mean of 13.8 days. Twenty-one patients were treated with ranitidine at a mean dose of 1.1 mg/kg/hr for a mean of 8 days. No patients suffered any complications related to acid hypersecretion or side effects of the H2 antagonists. Patients undergoing gastrinoma resection can be managed safely by continuous infusion of H2 antagonists. Successful gastrinoma resection can reduce acid output, but even 40% of biochemically cured patients will continue to hypersecrete acid at short-term follow-up and will require continuation of antisecretory medication.

Topics: Adult; Fasting; Female; Gastric Acid; Gastrinoma; Gastrins; Histamine H2 Antagonists; Humans; Infusions, Intravenous; Laparotomy; Male; Middle Aged; Osmolar Concentration; Pancreatic Neoplasms; Postoperative Period; Prospective Studies; Zollinger-Ellison Syndrome

Ten consecutive patients with metastatic gastrinoma that increased in size over time were studied prospectively during treatment with monthly cycles of streptozotocin (3 g/m2), 5-fluorouracil (1.2 g/m2), and adriamycin (40 mg/m2) to determine the response rate and time-courses of changes during chemotherapy and to assess various methods of evaluating the effect of chemotherapy. Forty percent of patients demonstrated an initial objective response (greater than or equal to 25% decrease in tumor size with no new lesions) and 60% failed chemotherapy (greater than or equal to 25% increase in tumor size or appearance of new lesions). The mean dose of streptozotocin was 27 g/m2 with objective responses occurring at 3.7 +/- 0.7 mo and failures at 4.5 +/- 0.7 mo. Responses lasted 9.7 +/- 2.8 cycles and no complete responses occurred. Survival was not significantly different in responders versus nonresponders (26 +/- 11 vs. 15 +/- 4.8 mo, p greater than 0.1). Changes in serum gastrin concentration, basal acid output, or sensitivity to a given dose of histamine H2-receptor antagonist did not reflect changes in tumor size. Computed tomography and angiography were the best methods to assess changes in tumor size during chemotherapy, whereas liver-spleen scan and ultrasound were relatively insensitive. All patients developed side effects with chemotherapy: 100% had vomiting, 80% alopecia, 40% transient proteinuria, and 20% leukopenia. The present results indicate that chemotherapy with streptozotocin, 5-fluorouracil, and adriamycin is much less effective in patients with extensive metastatic gastrinoma than previously reported. Computed tomography scanning is the method of choice to assess changes in tumor size. Changes in serum gastrin concentration, acid secretion, or tumor size assessed by liver-spleen scan or ultrasound are not sensitive indicators of the tumor response during chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Female; Fluorouracil; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Streptozocin; Zollinger-Ellison Syndrome

An analysis of data concerning 37 patients with the Zollinger-Ellison syndrome (ZES) has been made, 36 of them were operated upon. Gastrinoma was found in 21 patients. Diagnosis of ZES was made in two steps: the first one is fulfilled in general medical institutions, the second one-in specialized clinics. The diagnosis of ZES must be either confirmed or rejected with certainty. When choosing the method of operative treatment several groups of patients must be born in mind: ZES without a gastrinoma detected, ZES with a gastrinoma, ZES with malignant ulcerogenic tumour. The main operation for ZES remains to be gastrectomy.

Topics: Adult; Gastrectomy; Gastrinoma; Gastrins; Humans; Middle Aged; Pancreatic Neoplasms; Pyloric Antrum; Suture Techniques; Vagotomy; Zollinger-Ellison Syndrome

An ovarian gastrinoma would appear to be an extremely rare cause of the Zollinger-Ellison syndrome. Nevertheless, two consecutive cases of Zollinger-Ellison syndrome seen at our institution each proved to be caused by a gastrin-producing ovarian mucinous cystadenoma. That the ovarian tumor was the source of gastrin production was established by preoperative and postoperative gastrin and gastric secretory studies and by specific immunocytochemistry of the excised tissue. After oophorectomy, each patient was apparently cured of the disease. Ovarian gastrinomas may not be as uncommon as is generally believed and should be considered as a possible cause of the Zollinger-Ellison syndrome in any female patient in whom a primary gastrointestinal or pancreatic tumor cannot be located.

Topics: Adult; Cystadenoma; Female; Gastrinoma; Gastrins; Humans; Middle Aged; Ovarian Neoplasms; Zollinger-Ellison Syndrome

We report the first establishment and characterization of functioning gastrinoma from a human being transplanted into nude mice. Tissue was obtained at operation from a gastrinoma liver metastasis from a patient with the Zollinger-Ellison syndrome. The tumor was implanted subcutaneously in five athymic nude mice. Serum gastrin was measured by means of radioimmunoassay in specimens of mouse blood taken before and 5 minutes after intraperitoneal injection of secretin (100 micrograms/kg). In a second experiment serum gastrin was measured 30 minutes after injection of somatostatin analogue, SMS 201-995 (300 micrograms/kg). Studies were also done in 10 control mice. At passage, the fundus of each tumor-bearing mouse was weighed and examined microscopically. The gastrinoma (tumor line, PT) has been maintained for 34 months through four passages with a tumor doubling time of 37 to 45 days. The histology is similar to the original tumor. Immunocytochemistry showed that PT contained gastrin. In two mice metastasis developed 9 months after implantation. Gastrin levels in mice bearing PT have ranged from 216 to 12,000 pg/ml. Gastrin levels of control mice ranged from 0 to 63 pg/ml. Secretin increased gastrin levels in three of five mice tested and decreased gastrin levels in two mice. Repeat secretin tests showed identical results. SMS 201-995 decreased gastrin levels from basal values. Fundic weight of mice bearing PT (397 +/- 93 mg) was significantly greater than control fundic weight (180 +/- 26 mg). Gastrinomas growing in nude mice produce physiologically active gastrin as shown by elevated serum gastrin levels and by hyperplasia of the stomach. Two distinct subpopulations of gastrinoma cells respond differently to secretin. This model should provide important information on mechanisms of growth control and on gastrin release by gastrinomas in human beings.

Topics: Adult; Animals; Female; Gastrins; Humans; Mice; Mice, Nude; Microscopy, Electron; Neoplasm Transplantation; Octreotide; Secretin; Stomach; Transplantation, Heterologous; Zollinger-Ellison Syndrome

Because beta-adrenoreceptor agonists inhibit gastrin-stimulated gastric acid secretion in animals, we postulated that the beta 2-adrenoreceptor agonist, terbutaline, would inhibit pentagastrin-stimulated acid secretion in humans. Moreover, we hypothesized that terbutaline might inhibit food-stimulated acid secretion, as gastrin is a major mediator of food-stimulated acid secretion. Subcutaneous terbutaline (0.25 mg) reduced acid secretion during intravenous infusion of a submaximal dose of pentagastrin by 30%-40% (p less than 0.005), even though terbutaline increased serum gastrin levels (p less than 0.05). Furthermore, subcutaneous (0.25 mg) or oral (5 mg) terbutaline, given before a homogenized steak meal was infused into the stomach, lowered mean food-stimulated acid secretion rates, despite enhanced postprandial serum gastrin concentrations. Terbutaline also increased serum gastrin concentrations in patients with Zollinger-Ellison syndrome and in vagotomized individuals. Thus, beta 2-adrenoreceptor agonists enhance gastrin release while at the same time inhibiting gastrin-stimulated acid secretion in humans.

Topics: Adult; Eating; Female; Gastric Acid; Gastrins; Humans; Injections, Subcutaneous; Male; Middle Aged; Premedication; Propranolol; Terbutaline; Zollinger-Ellison Syndrome

Prognosis of gastrinoma patients with metastases to lymph nodes only is uncertain, and the true nature of isolated nodal gastrinomas remains controversial. The purpose of this study was to determine the outcome of such patients and whether nodal gastrinomas may occur as primary lesions. Eleven patients with nodal involvement but without hepatic metastases are reported (mean follow-up of 129 months). Primary gastrinomas were located in the duodenum in seven (Group 1) and not identified in four (Group 2). In Group 1, five patients remained eugastrinemic after excision of all gross tumors and gastrectomy (n = 4) or pancreaticoduodenectomy (n = 1), one patient had residual disease and died of other causes (survival of 88 months), and one patient had MEA-I syndrome with multiple gastrinomas (follow-up of 126 months). In Group 2, three patients became eugastrinemic after nodal excision and total gastrectomy (mean follow-up of 212 months) and may represent primary nodal gastrinomas, and in one patient, liver metastases developed and the patient died. Four deaths occurred in a 27-year period, but only one was tumor-related. There was no significant difference in 20-year survival rates between the two groups (85% vs. 75%). It is concluded that 1) lymph node gastrinomas are usually metastatic from primary duodenal lesions, 2) although rare, nodal gastrinomas may occur as primary lesions, and 3) in the absence of hepatic metastases, lymph node gastrinomas, whether primary or metastatic, have a good prognosis and should not deter aggressive surgical treatment.

Topics: Adolescent; Adult; Aged; Duodenum; Female; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Pancreatectomy; Prognosis; Zollinger-Ellison Syndrome

Nine patients with pancreatic apudomas (seven gastrinomas, one glucagonoma, one tumor secreting a substance P-like component) and nine with metastasized carcinoid tumors were treated with a somatostatin analogue (SMS 201-995), administered subcutaneously twice daily for 3 days. Treatment was pursued for 2 to 12 months in nine patients in whom SMS was clinically and/or biologically beneficial. In gastrinomas, SMS decreased plasma gastrin in all but one patient, inhibited the residual gastric acid secretion under H2-blockers and improved diarrhea; in the glucagonoma patient, glucagonemia decreased and skin lesions disappeared. In carcinoid syndrome, clinical efficacy was partial and inconstant; daily 5-hydroxyindole acetic acid (5-HIAA) output was slightly decreased. Plasma substance P levels decreased in six patients with initially high concentrations. No antitumoral activity or side effects have been so far evidenced. SMS 201-995 is a useful, well-tolerated agent in secreting pancreatic apudomas and to a lesser extent in carcinoid syndrome, where high-dosage regimens may be required.

Topics: Adult; Aged; Carcinoid Tumor; Female; Gastric Juice; Gastrins; Glucagonoma; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Somatostatin; Substance P; Zollinger-Ellison Syndrome

Topics: Adult; Carcinoid Tumor; Female; Gastrins; Glucagon; Glucagonoma; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Pancreatic Neoplasms; Serotonin; Somatostatin; Zollinger-Ellison Syndrome

A tissue specimen taken from the pancreatic tumor of a patient suffering from Zollinger-Ellison syndrome associated with a concurrent Cushing's syndrome was investigated both morphologically and immunohistochemically. Histologically, the tumor cells were found to be arranged in a cord or ribbon pattern. An immunohistochemical study revealed that the tumor nodule contained both gastrin and ACTH. Further, double stainings of the same section disclosed that the same tumor nodule possessed both hormones simultaneously, thus confirming the concurrent presence of Zollinger-Ellison syndrome and Cushing's syndrome. An electron micrograph of the tumor cell showed the presence of numerous endocrine-type granules in the cytoplasm. These findings substantiate the concurrent presence of the two characteristic clinical syndromes.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Gastrins; Humans; Male; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Medical treatment of the Zollinger-Ellison syndrome has been generally accepted because of the proven efficacy of the histamine (H2)-receptor antagonists in achieving symptomatic relief, and because of early reports indicating that few, if any, gastrinomas were resectable for cure. Gastrin radioimmunoassay (RIA) has made earlier and more certain diagnosis possible, and therefore reevaluation of the surgical management of gastrinomas is necessary. Experience with 60 gastrinoma patients is reported. Comparison between the pregastrin RIA years (before 1970) and post-gastrin RIA years was made to determine whether there was evidence to support the continuation of medical treatment without attempts to resect the gastrinoma. Twenty-five cases were diagnosed in the pre-RIA years. Age at diagnosis ranged from 17 to 68 years (median, 45 years). All patients were operated on. Metastases were found in 56 percent. No tumor was identified in 8 percent. Tumor was resected for "cure" (normal fasting gastrin levels for two years postoperatively) in one patient. Seventeen patients have died, and tumor was the cause of death in 70 percent. The five-year survival rate was 44 percent; the 10-year survival rate was 40 percent. Thirty-five cases were diagnosed after 1970. Age at diagnosis ranged from 39 to 61 years (median, 46 years). Thirty patients were operated on. Metastases were identified in 23 percent and no tumor was found in 17 percent. Tumor was resected for "cure" in 30 percent of patients. Seven patients have died and tumor caused death in 42 percent. The five-year survival rate was 82 percent; the 10-year rate was 64 percent. Advances in diagnosis and surgical technique since 1970 have made early operative treatment applicable in patients with gastrinoma. Because death in most cases is caused by progression of the tumor, an aggressive surgical approach to resect the tumor is advised soon after the diagnosis of Zollinger-Ellison syndrome is established.

Topics: Duodenal Neoplasms; Follow-Up Studies; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Prognosis; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Radionuclide Imaging; Somatostatin; Zollinger-Ellison Syndrome

Two cases of multiple islet cell tumors mostly composed of glucagon-producing cells and associated with severe ulcer disease are presented. Multiple endocrine neoplasia type I (MEN-I) was present in both patients, although symptomatically latent in case 2. Immunohistochemistry showed that glucagon (A) cells were a major cell population (i.e., accounting for at least 30% of the tumor cell population) in 24 of 43 tumors (either macroadenomas or microadenomas) studied in case 1 and in 12 of 17 tumors studied in case 2. A major pancreatic polypeptide (PP) cell population was found in 12 and 7 tumors of case 1 and 2, respectively. In contrast, insulin (B) and somatostatin (D) cells were scarce in most adenomas. Gastrin-producing cells were not identified in any tumors, despite the use of different antigastrin antisera. Extrapancreatic or residual gastrinomas were not found at postmortem examination in case 1 or on appropriate surgical inspection done 24 years after the onset of the ulcer disease in patient 2. On the basis of these and of 17 additional cases collected in the literature, it is concluded that multiple A-cell tumors of the pancreas are an expression of the MEN-I and are mostly associated with ulcer disease and/or with hypergastrinemia of frequent uncertain origin. The mechanisms regulating the nonrandom phenotypic hormonal differentiation of these genetically determined tumors remain unknown.

Topics: Adult; Female; Gastrins; Glucagon; Humans; Middle Aged; Multiple Endocrine Neoplasia; Zollinger-Ellison Syndrome

Topics: Adult; Calcium; Child; Diagnosis, Differential; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatectomy; Postoperative Care; Time Factors; Vagotomy; Zollinger-Ellison Syndrome

This study evaluates prospectively the effect of parathyroidectomy on basal acid output (BAO), maximal acid output (MAO), fasting serum gastrin, secretin-stimulated serum gastrin, and sensitivity to antisecretory medication in 10 consecutive patients with primary hyperparathyroidism (PHP), Zollinger-Ellison syndrome (ZES), and multiple endocrine neoplasia type I (MEN-I). After parathyroidectomy, 9 of 10 patients remained normocalcemic, and each had a lower BAO; 6 of 9 no longer had gastric acid hypersecretion (less than 15 mEq/hr). Seven of 9 normocalcemic patients had a lower MAO, and a decrease in fasting serum gastrin. Two patients showed no evidence of ZES, a normal BAO, normal fasting serum gastrin concentration, and a negative secretin response after parathyroidectomy. Parathyroidectomy also reduced the dose of histamine H2-receptor antagonist required to control gastric acid secretion in 60% of patients. After successful parathyroidectomy three patients were studied for drug sensitivity, and each had greater acid inhibition with a given dose of histamine H2-receptor antagonist than preoperatively. One patient remained hypercalcemic after surgery and had no change in BAO, MAO, or gastrin. All patients with postoperative normocalcemia will have a lower BAO, 80% a lower MAO, 80% a decreased fasting serum gastrin, and 33% a negative secretin test. Antisecretory medication dose can be reduced because patients have reduced BAO and increased sensitivity to histamine H2-receptor antagonist. The study supports parathyroidectomy as the initial surgical procedure of choice in patients with PHP, ZES, and MEN-I.

Topics: Adult; Female; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Parathyroid Glands; Prospective Studies; Zollinger-Ellison Syndrome

Somatostatin analogue (SMS 201-995) has been shown to decrease total serum gastrin in patients with gastrinoma; however, the gastrin level rarely returns to normal, despite the near-complete inhibition of acid secretion. This implies that SMS may have an inhibitory action on the biologically active molecular species of gastrin and have little effect on biologically inactive species. To test this hypothesis, we determined the effect of SMS on the molecular species of gastrin in eight patients with the Zollinger-Ellison syndrome. Serum obtained before treatment and 6 hours and 18 hours after treatment (SMS 1 microgram/kg, subcutaneously) was sampled and assayed for molecular species of gastrin by means of gel filtration chromatography and fractional quantitation of gastrin species by radioimmunoassay. There was a significant decrease in the amount of G-34 and G-17 species. BBG and G-14 decreased, a change not significant at 6 hours but significant 18 hours after SMS. The distribution of the various molecular species as a percent of total immunoreactive gastrin was analyzed before and after SMS. There was a shift in the distribution of the molecular species, so that 6 hours after SMS treatment nearly 50% of total gastrin activity was accounted for by BBG and component I. SMS seems to have a different potency to inhibit release of the various gastrin molecular species. This observation may explain the failure of total gastrin levels to return to normal after SMS treatment in patients with the Zollinger-Ellison syndrome.

Topics: Aged; Chromatography, Gel; Female; Gastrins; Humans; Male; Middle Aged; Octreotide; Somatostatin; Zollinger-Ellison Syndrome

Topics: Adult; Gastrins; Hormones, Ectopic; Humans; Insulin; Liver Neoplasms; Male; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Secretin was injected into a feeding or nonfeeding artery of a gastrinoma and blood samples were taken from the hepatic vein (HV) or a peripheral artery (PA) to measure the changes of serum immunoreactive gastrin concentration (IRG). The IRG in the HV rose within 40 seconds and in the PA rose within 60 seconds after the injection of secretin into a feeding artery, but not after secretin was injected into a nonfeeder. These results indicated that secretin directly stimulates a gastrinoma to release gastrin in vivo. The selective arterial secretin injection test (SASI test) was applied in three patients in whom gastrinomas could not be located by computed tomography, ultrasonography, or arteriography, and functioning gastrinomas were located in all three patients. In one patient, malignant gastrinomas in the head of the pancreas and in the duodenum could be resected radically with the help of this test.

Topics: Adult; Aged; Angiography; Duodenal Neoplasms; Female; Gastrins; Histocytochemistry; Humans; Insulin; Laparotomy; Liver Neoplasms; Male; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

Antibodies to different peptides produced from the gastrin precursor have been used in light microscopic- and electron microscopic-immunogold studies of gastrinoma tissue and normal antral mucosa. Antibodies to the C terminus of progastrin, which are known to react with the intact precursor, revealed immunoreactive material in the rough endoplasmic reticulum, Golgi region, and electron-dense granules in gastrinoma cells. In normal antrum these antibodies again revealed the Golgi region and a population of electron-dense granules. Other antibodies that react with the products of progastrin processing, but not the precursor, e.g., C-terminal and N-terminal gastrin 17 specific antibodies, revealed only granules. In addition to electron-dense granules already mentioned, the latter antibodies also revealed electron-lucent and intermediate granule populations, which in antrum were the major granule types. It is proposed that the intact precursor occurs in rough endoplasmic reticulum and Golgi; thereafter, in the immature electron-dense granules, and subsequently in electron-lucent granules, biosynthetic processing liberates gastrin 17 and gastrin 34, which are the major active products of gastrin gene expression.

Topics: Gastrins; Gold; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunoglobulin G; Protein Precursors; Pyloric Antrum; Zollinger-Ellison Syndrome

The molecular species of gastrin in the circulation and in tumor extracts were studied in two groups of patients: (1) with benign gastrinoma and (2) with gastrinoma with liver metastases. Radioimmunoassays (RIAs) and immunoaffinity chromatography for the amino (NH2)- and amidated COOH-terminus of gastrin-17 (antiserum G17) and the NH2-terminus of gastrin-34 (antiserum G34) were employed. In both benign and metastatic tumors the molecular forms of gastrin in boiling water extracts measured by the gastrin-17 NH2- and COOH-terminal assays were similar. In addition to a molecular component resembling the amidated gastrin-17, there were also significant amounts of larger molecular weight (mol. wt.) forms. The larger mol. wt. forms absorbed by the NH2-terminus of G17 antiserum corresponded to the COOH-terminus-extended forms of gastrin-17. Furthermore, larger mol. wt. gastrins immunopurified by antiserum to the NH2-terminus of gastrin-34 corresponded to gastrin-34 extended molecules. Sera of patients with liver metastases had higher concentrations of the NH2-terminal of gastrin-17 whereas sera of patients with benign gastrinoma contained predominantly gastrins detected by the COOH-terminal assay. These results suggest that: (a) there are differences in the molecular pattern of gastrin in the circulation of patients with benign and metastatic gastrinomas; (b) gastrins which are fully processed with carboxy-terminal amidation predominate in the circulation of patients with benign gastrinoma; and (c) gastrins containing the gastrin-17 and COOH-terminally extended gastrin-17 and gastrin-34 precursor molecules occur in high concentration in the circulation of gastrinoma patients with metastases to the liver.

Topics: Chromatography, Gel; Gastrins; Humans; Immune Sera; Immunosorbent Techniques; Liver Neoplasms; Molecular Weight; Radioimmunoassay; Zollinger-Ellison Syndrome

We examined the posttranslational modification of gastrin in human gastrointestinal and Zollinger-Ellison tumor tissues using antibodies specific for progastrin and its glycine-extended processing intermediates. Gel filtration of antral and duodenal extracts on Sephadex G-50 revealed multiple molecular forms of immunoreactive glycine-extended processing intermediates corresponding to known molecular forms of gastrin and cholecystokinin. Immunoaffinity chromatography studies of antral mucosal and gastrinoma extracts identified a molecular form of glycine-extended processing intermediates that was characterized by an amino terminus identical to that of gastrin heptadecapeptide. Large differences in the relative contents of precursors and products of gastrin synthesis were found in gastrinoma tissue as compared to gastrointestinal mucosal extracts. These studies suggest the potential importance of glycine-extended peptides as intermediates in the posttranslational processing of gastrin and cholecystokinin in humans and indicate that gastrin processing mechanisms may be altered in Zollinger-Ellison tumors.

Topics: Chromatography, Affinity; Chromatography, Gel; Digestive System; Gastrins; Humans; Protein Precursors; Protein Processing, Post-Translational; Radioimmunoassay; Zollinger-Ellison Syndrome

From 1971-1986, 24 patients were diagnosed as having Zollinger-Ellison syndrome (ZES) and 22 patients had laparotomy. Of this group, gross tumor was identified in 15 of 22 patients. Ten of 15 patients had resection of their gastrinomas with the specific aim of curing the disease. This group had responded favorably to either cimetidine or ranitidine before operation. Preoperative transhepatic portal venous sampling (PVS) with gastrin determinations was performed in six patients; three patients had this procedure twice. The tumor was correctly localized by PVS in five of six patients. In four of six patients, the tumor was easily found at surgery. In two of six patients (33%) PVS was vital to intraoperative decisions. Criteria for biochemical cure are normal periodic fasting gastrin and secretin infusion tests. Of the 10 patients who had resection for potential cure, two patients failed within 48 hours of surgery on the basis of an elevated fasting serum gastrin level in one patient and a positive secretin infusion test in the other patient. Eight patients were considered cured with follow-up from 6 months through 15 years. Of the eight cured patients, the tumors were located as follows: four were extraintestinal and extrapancreatic, four were in the duodenal wall, one patient had a tumor located in the uncinate process of the pancreas, and one tumor was located in a lymph node along the lesser curve of the stomach. Two patients had mobilization of the pancreas and duodenum for a "blind" pancreatoduodenectomy based on preoperative PVS (2 procedures each patient). In one patient a 3-mm gastrinoma was enucleated from the posterior uncinate process. The second patient had pancreatoduodenectomy with findings of two duodenal wall gastrinomas. Both patients remained cured of ZES beyond 2 years. It is concluded that PVS does indeed locate some tumors before operation, even those not easily found at surgery. ZES can be cured by an aggressive approach combining preoperative tumor localization and tumor resection. Of the eight patients biochemically and perhaps biologically cured, follow-up was greater than four years in five patients, greater than two years in two patients, and beyond six months in one patient.

Topics: Duodenal Neoplasms; Gastrectomy; Gastrins; Humans; Laparotomy; Lymphatic Metastasis; Portal Vein; Retrospective Studies; Zollinger-Ellison Syndrome

The intravenous secretin test is widely used to distinguish gastrinoma (Zollinger-Ellison syndrome) from other causes of fasting hypergastrinemia. We report 2 patients with fasting hypergastrinemia and a rise of greater than 200 pg/ml in serum gastrin concentration after intravenous injection of 2 CU/kg body wt of pure natural secretin. Both patients had pentagastrin-fast achlorhydria. Thus, the intravenous secretin test may be positive in patients with achlorhydria-related hypergastrinemia. Gastric acid secretion should be measured in hypergastrinemic patients before embarking on a secretin test.

Topics: Achlorhydria; Cross Reactions; False Positive Reactions; Female; Gastrins; Humans; Middle Aged; Secretin; Zollinger-Ellison Syndrome

A patient with metastatic gastrinoma whose plasma gastrin ranged from 7.6 nmol X ml-1 at presentation to 18.9 nmol X ml-1 just before death 4 yr later has been studied. The presence of such high circulating levels facilitated study of the biological and immunological activities as well as the molecular forms of gastrin in plasma, ascitic fluid, urine and cerebrospinal fluid. The results indicate: 1) the 34 amino acid gastrin (G34) was the only molecular form detectable in the body fluids studied; 2) bioactivity of G34 is maintained despite passage across the renal endothelium and the blood brain barrier; 3) the blood brain barrier significantly limits diffusion of G34.

Topics: Adult; Ascitic Fluid; Female; Gastrins; Humans; Zollinger-Ellison Syndrome

The role of endogenous gastrin in the pathogenesis of "idiopathic" ulcer disease is difficult to determine; however, gastrin is probably only of limited importance besides various probable more important factors. In conditions associated with uncontrolled gastrin production by a gastrin secreting tumor or in cases in which the feedback regulation between gastrin release and intragastric pH is disturbed severe and recurrent ulcers may develop. Radioimmunological determination of serum gastrin levels enable to identify such cases of ulcer disease due to an excess of circulating gastrin.

Topics: Gastric Acid; Gastrins; Humans; Pancreatic Neoplasms; Peptic Ulcer; Recurrence; Zollinger-Ellison Syndrome

Antibodies to the extreme C-terminal region of human progastrin have been used to monitor the isolation of high-Mr immunoreactive material in a gastrinoma extract. Microsequence analysis of the product revealed amino acid residues in the first 18 positions corresponding to those predicted from the cDNA sequence for preprogastrin starting at position 22; the sequence and immunochemical data together allow the identification of this material as intact progastrin. Implications for gastrin biosynthesis are discussed.

Topics: Amino Acid Sequence; Gastrins; Humans; Liver Neoplasms; Protein Precursors; Zollinger-Ellison Syndrome

Pseudo-Zollinger--Ellison syndrome appears to very rarely afflict young children. Hypergastrinemia, regardless of the etiology, presents with signs and symptoms of nonhealing or multiple gastric or duodenal ulcers, or both. We present a 7-yr-old boy with fasting hypergastrinemia (serum gastrin 200-500 pg/ml) who had mild to moderate iron deficiency anemia, but was asymptomatic. Stool guaiac was positive and gastric acid secretion was almost 40-fold above normal. Endoscopy showed multiple small gastric fundal ulcerations and severe gastritis. Workup for Zollinger--Ellison syndrome was negative. Changes in serum gastrin levels after secretin injection and after ingestion of a protein meal were compatible with those noted in adults with pseudo-Zollinger--Ellison syndrome. This child may be the first case of pseudo-Zollinger--Ellison syndrome under the age of 17 yr.

Topics: Anemia, Hypochromic; Child; Gastric Acid; Gastrins; Humans; Male; Occult Blood; Zollinger-Ellison Syndrome

Management of patients with multiple endocrine neoplasia type I (Wermer's syndrome) who have concurrent hypercalcemia and hypergastrinemia is controversial. The usual therapeutic approach has been to perform parathyroidectomy first before surgery for ulcer disease in an effort to decrease serum calcium concentration and presumably remove one of the stimuli for both gastrin and gastric acid secretion. We present the history of a 48-year-old man with primary hyperparathyroidism and Zollinger-Ellison syndrome who underwent acid secretory studies and secretin stimulation tests before and after parathyroidectomy. We also studied the effect of calcium channel blockade on gastrin and gastric acid secretion, since calcium influx into endocrine cells, such as the gastrinoma cell, is thought to be critical in hormone secretion. Although parathyroidectomy reduced serum calcium and parathormone levels to normal, basal serum gastrin concentration and basal acid output remained unchanged. The peak rise in serum gastrin concentration after secretin injection was less after parathyroidectomy than before parathyroidectomy but was still abnormal. During administration of verapamil, a calcium channel antagonist, no change was seen in the serum gastrin concentration, secretin test response, or acid secretion. Basal acid output was 45.4 mmol/hr before parathyroidectomy or verapamil and 54.0 and 50.4 mmol/hr after parathyroidectomy or verapamil, respectively. In contrast, a small but significant decrease (p less than 0.05) in serum parathormone concentration occurred during treatment with verapamil, an observation that to the best of our knowledge has not been previously reported in humans.

Topics: Calcium Channel Blockers; Gastric Acid; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Glands; Pedigree; Peptic Ulcer; Verapamil; Zollinger-Ellison Syndrome

The secretin provocation test for gastrinoma is based on the premise that secretin decreases or has no effect on serum gastrin in normal and duodenal ulcer subjects while inducing a paradoxical rise in gastrinoma. We reexamined the serum gastrin response to pharmacologic amounts of secretin in normal volunteers (N = 17) and unoperated duodenal ulcer patients (N = 10). GIH secretin caused significant early gastrin rises from baseline in both groups (P less than 0.05). The gastrin response curves after secretin were not significantly different between normal and ulcer subjects. Similar gastrin rises were seen when synthetic secretin was administered to normal subjects (N = 6). In normal volunteers, intravenous bolus saline (N = 10) or amino acid (L-cysteine, N = 8) caused no change in serum gastrin from baseline. The gastrin response curves to GIH secretin and saline were significantly different (P less than 0.05). Our findings suggest that the gastrin rise in gastrinoma patients after secretin is an exaggeration of the normal response and not paradoxical.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Secretin; Time Factors; Zollinger-Ellison Syndrome

Somatostatin is known to inhibit hormone release and gastrointestinal secretion and hence may be useful in the treatment of amine precursor uptake, decarboxylase tumors. Clinical application has been limited by the short half-life, potency, and specificity of the natural hormone. Our study evaluated the effect of a synthetic analog of somatostatin, SMS 201-995 (Sandoz, Inc., E. Hanover, N.J.) on basal and stimulated gastrin release and gastric acid secretion in 10 patients with the Zollinger-Ellison syndrome. In experiment 1, H2-receptor antagonists were discontinued for 48 hours; SMS 201-995, 1 microgram/kg, was given subcutaneously; gastrin and SMS levels in plasma were determined by radioimmunoassay; and gastric secretion was measured and titrated at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 18 hours. The mean +/- SEM baseline gastrin level (1526 +/- 733 pg/ml) was significantly inhibited for 16 hours (p less than 0.05, paired t test). Gastric secretion was neutralized for as long as 18 hours (p 0.05). In experiment 2, three patients received either a secretin (2 U/kg) or a calcium stimulation test (2 mg/kg) with or without pretreatment with SMS 201-995, 1 microgram/kg, subcutaneously. The mean +/- SEM interpreted change in gastrin (ng X 60 min/ml) without SMS 201-995, 36.8 +/- 11 (secretin), and 129 +/- 30 (calcium) were reduced with SMS 201-995 to -1.1 +/- 0.76 (secretin) and -29 +/- 28 (calcium) (p less than 0.05). In the Zollinger-Ellison syndrome, SMS 201-995 caused significant and long-lasting inhibition of both tumor gastrin release and gastric acid secretion, probably by direct action on both the gastrinoma and the stomach. SMS 201-995 blocks acid secretion and secretin- and calcium-stimulated gastrin release, indicating that SMS 201-995 inhibits peptide secretion by postreceptor mechanisms. SMS 201-995 will be useful in the palliative treatment of apudomas.

Topics: Adult; Aged; Antineoplastic Agents; Apudoma; Calcium; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Octreotide; Palliative Care; Receptors, Opioid; Secretin; Somatostatin; Stimulation, Chemical; Time Factors; Zollinger-Ellison Syndrome

A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.

Topics: Adult; Antineoplastic Agents; Calcitonin; Carcinoma; Dose-Response Relationship, Drug; Drug Evaluation; Female; Gastrins; Humans; Male; Octreotide; Palliative Care; Postoperative Care; Somatostatin; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Forty-six patients with the gastrinoma syndrome were divided into 2 categories: 1) benign sporadic gastrinoma (n = 30), and 2) gastrinoma with metastases to liver (n = 16). Thirteen of the 46 patients had multiple endocrine neoplasia type I syndrome. Serum gastrin levels in patients fasted overnight were determined by RIA using antisera directed toward the NH2- and COOH-terminals of heptadecapeptide gastrin (G17) and the NH2-terminus of the triacontatetrapeptide (G34). These results were compared with findings in 50 normal subjects. In the normal subjects, the mean COOH-terminal gastrin-17 level was higher [65 +/- 8 (+/- SEM) pg/ml] than the NH2-terminal gastrin-17 level (11 +/- 0.2 pg/ml) and lower than the NH2-terminal gastrin-34 level (134 +/- 20 pg/ml). The levels of NH2-terminal gastrin-17 were higher in patients with metastatic disease than in those with benign gastrinoma, whereas the COOH-terminal gastrin-17 and the NH2-terminal gastrin-34 levels were similarly high in both groups. The mean ratio of NH2-terminal gastrin-17 to COOH-terminal gastrin-17 was less than 1 in normal subjects (0.22 +/- 0.02) and benign gastrinoma patients (0.2 +/- 0.04), and it was 2.2 +/- 0.41 in the patients with metastatic gastrinoma. An NH2 to COOH gastrin-17 ratio greater than 1 was found in 13 of 16 patients with metastatic gastrinoma, but in none of the patients with benign gastrinoma or normal subjects. Similar results were found in multiple endocrine neoplasia type I patients with benign and metastatic disease. A high NH2 to COOH gastrin-17 ratio is suggestive of metastatic gastrinoma. In 4 patients with metastatic gastrinoma, the NH2 to COOH gastrin-17 ratio fell in parallel with the response to chemotherapy.

Topics: Chromatography, Gel; Gastrins; Humans; Liver Neoplasms; Multiple Endocrine Neoplasia; Protein Precursors; Radioimmunoassay; Zollinger-Ellison Syndrome

It is argued that all chronic gastroduodenal peptic ulcers result from localised increase in mucosal susceptibility to acid attack at the interface between a segment of gastroduodenitis and gastric fundus or duodenal mucosa. The site is predetermined by the background mucosal pattern. Changes can occur in the differentiated gastroduodenal mucosa that closely resemble cell population transformations described in embryology and regeneration biology. A second pathological process, gastroduodenitis, may develop that does not of itself predispose to ulceration, but the combination of factors can produce a zone of increased acid susceptibility. These complex changes could be generated by immunologically activated gastroduodenitis. Destructive or stimulatory immune reactions, analogous to those seen in the thyroid gland, could affect the gastrin-secreting G cells and other paracrine cells. The resulting tropic and inflammatory reactions would provide the background for peptic ulceration.

Topics: Autoantibodies; Chronic Disease; Duodenitis; Duodenum; Gastric Fundus; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Intestinal Mucosa; Parietal Cells, Gastric; Peptic Ulcer; Zollinger-Ellison Syndrome

Between 1971 and 1983, 31 males and 13 females were found to have peptic ulceration associated with hypergastrinaemia. An antral G-cell lesion was present in 11 (25 per cent) and a gastrinoma in 14 (32 per cent). There were 11 patients with multiple endocrine adenomatosis (MEA) (25 per cent) and 4 (9 per cent) with primary hyperparathyroidism. Four patients (9 per cent) were unclassified. Length of history and level of gastrin did not differentiate between the groups and an average of 2.5 operations was performed per patient, while the overall mortality was 27.3 per cent. The patients with G-cell lesions were significantly younger than all the other groups (P less than 0.01). Partial gastrectomy adequately treated G-cell hyperplasia. Total gastrectomy was required to treat pancreatic gastrinomata but additional pancreatic resection did not improve the outcome. In MEA, parathyroidectomy did not influence the treatment of a gastrinoma. This is the first recorded experience of surgery for hypergastrinaemia in the United Kingdom and the outcome of such a retrospective study may be a guide to the future management of these conditions.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Female; Gastrectomy; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatectomy; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Blood Glucose; Female; Gastrins; Humans; Insulinoma; Male; Octreotide; Pancreatic Neoplasms; Somatostatin; Vipoma; Zollinger-Ellison Syndrome

Topics: Female; Gastrins; History, 20th Century; Humans; Hyperparathyroidism; Male; Multiple Endocrine Neoplasia; Secretin; Zollinger-Ellison Syndrome

The provocation of gastrin release by calcium or secretin is accepted as a method to differentiate the hypergastrinemia of the Zollinger-Ellison syndrome from that of other causes. We have previously shown that calcium and secretin failed to provoke gastrin release from acutely dispersed gastrinoma cells. This disparity between the in vivo and in vitro effects of these two provocative agents suggests that intermediates may be necessary for calcium- or secretin-induced gastrin release. In an acute cell dispersion, serum-free model, two gastrinomas with low levels of endogenous somatostatin (SRIF) and other peptides failed to respond to calcium or secretin provocation. Conversely, a third tumor containing high levels of endogenous SRIF-like peptides and low levels of other gut peptides did respond to calcium, but not to secretin provocation in vitro. We suggest that in vivo, SRIF modulation of gastrin release is a prerequisite for calcium-simulated gastrin secretion.

Topics: Animals; Calcium; Gastrins; Humans; Rats; Secretin; Somatostatin; Zollinger-Ellison Syndrome

Acromegaly is rarely caused by the ectopic secretion of growth hormone releasing factor (GRF) from peripheral neuroendocrine tumours. We evaluated the ability of a recently developed somatostatin analogue (SMS 201-995, Sandoz) to reduce hormone levels and pituitary size in a young woman with acromegaly and Zollinger-Ellison syndrome secondary to a metastatic pancreatic islet cell tumour secreting GRF and gastrin. Gastrin, GRF, and growth hormone (GH) levels declined dramatically following the initiation of therapy with the analogue by continuous iv infusion. Although intermittent sc therapy was not effective in suppressing hormone levels, continuous sc infusion of SMS 201-995 has provided good control of both GRF and GH levels for nine months. Moreover, treatment with SMS 201-995 was associated with a substantial reduction in pituitary enlargement and an improvement in her gastric symptoms. Continuous sc infusion of SMS 201-995 may be useful in treating enlarged pituitaries resistant to other modes of therapy.

Topics: Acromegaly; Adenoma, Islet Cell; Adult; Female; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Octreotide; Pancreatic Neoplasms; Somatostatin; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatectomy; Veins; Zollinger-Ellison Syndrome

A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D-cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G-cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D-cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Synergism; Enprostil; Female; Gastric Acid; Gastrins; Histocytochemistry; Humans; Immunoenzyme Techniques; Middle Aged; Prostaglandins E, Synthetic; Ranitidine; Serotonin; Somatostatin; Zollinger-Ellison Syndrome

Earlier experiments characterized the effect of SMS 201-995 on gastrin secretion from gastrinoma in vivo. The results showed that the somatostatin analogue inhibits basal as well as secretin- and calcium-stimulated gastrin secretion. The current study examined the effect of SMS 201-995 on gastrin secretion from gastrinoma in vitro. Gastrinoma cells were prepared in cell culture or acute cell dispersion to study basal gastrin release. In cell culture, SMS 201-995 at 10(-9) M, 10(-8) M, and 10(-7) M significantly stimulated gastrin secretion (basal medium gastrin, 157 +/- 7.9 pg/ml; with SMS 201-995 10(-9) M, 786 +/- 62 pg/ml; with SMS 201-995 10(-8) M, 569 +/- 72 pg/ml; and with SMS 201-995 10(-7) M, 258 +/- 26 pg/ml). In contrast, in acute cell dispersion, the somatostatin analogue inhibited gastrin secretion (basal medium gastrin, 12.8 +/- 1.3 ng/ml; with SMS 201-995 10(-9) M, 9.0 +/- 0.1 ng/ml; with SMS 201-995 10(-8) M, 8.4 +/- 1.5 ng/ml; and with SMS 201-995 10(-7) M, 7.9 +/- 0.2 ng/ml). Gastrinoma cells were prepared in cell culture to study the effect of SMS 201-995 on gastrin secretion stimulated by secretin and by post-receptor increases in adenosine cyclic nucleotide. The somatostatin analogue inhibited gastrin secretion stimulated by secretin (10(-6) M) (797 +/- 48 pg/ml for secretin alone, compared with 396 +/- 9.4 pg/ml for secretin plus SMS 201-995). SMS 201-995 did not inhibit gastrin secretion stimulated by dibutyryl cyclic AMP (10(-7) M) (617 +/- 62 pg/ml for dibutyryl cyclic AMP alone, compared with 778 +/- 55 pg/ml for the two together). In vitro, SMS 201-995 inhibits basal gastrin secretion from gastrinoma prepared in acute cell dispersion, but not gastrinoma in cell culture, probably due to differences in basal secretory rates. The effect in vitro is less than that in vivo. SMS 201-995 does not inhibit postreceptor increases in adenosine nucleotide. This indirectly supports the hypothesis that SMS 201-995 acts in gastrinoma cells to inhibit gastrin secretion by inhibition of adenylate cyclase activity.

Topics: Adult; Antineoplastic Agents; Bucladesine; Gastrins; Humans; In Vitro Techniques; Male; Octreotide; Secretin; Somatostatin; Zollinger-Ellison Syndrome

Fifteen patients with Zollinger-Ellison syndrome followed at the National Institutes of Health with extensive metastatic disease had an actuarial 5-year survival of 20%. Therefore, in 1982 a prospective study to examine the effect and feasibility of removing all gross tumor in selected patients with extensive metastatic disease was instituted. Five patients with extensive metastatic gastrinoma confined to the abdomen in whom imaging studies suggested the possibility of complete surgical resection were entered into this study and underwent attempted complete surgical resection and chemotherapy with streptozotocin, doxorubicin, and 5-fluorouracil. Median follow-up was 24 months. Surgical resection of all gastrinoma was possible in 4/5 patients attempted. In one patient in whom all gross disease could not be resected, the residual tumor progressed and the patient died 19 months after operation. All four patients with all disease resected appeared to benefit since all of them had a significant reduction in antisecretory medications and are enjoying normal activity and work. Three patients have had no detectable tumor on follow-up, and two of these patients are clinically and biochemically "cured" with normal fasting gastrin levels and negative provocative gastrin tests at 14 and 32 months. Therefore, aggressive resection of metastatic disease in selected patients with malignant gastrinoma is recommended.

Topics: Abdominal Neoplasms; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cimetidine; Combined Modality Therapy; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Gastrins; Humans; Kidney Neoplasms; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Prospective Studies; Radiography; Ranitidine; Streptozocin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Insulinoma; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

The complete sequence of the human gastrin gene is reported here. This gene consists of three exons. Nine Alu family sequences are found within the gene and in the surrounding region. S1 mapping study showed that the transcription of gastrin gene starts at 60, 57, or 55 bp upstream from the 3' end of the first exon. The mechanism of mRNA synthesis in a gastrinoma tissue was studied to clarify the ectopic production of gastrin. It was found that mRNA synthesis starts from the same three transcriptional start points. Southern blotting profiles for normal gastric antrum and gastrinoma DNA were indistinguishable from each other within the 18-kb region containing the gastrin gene, showing that no genomic rearrangements are associated with the gastrinoma formation. Thus, the overproduction of gastrin in this tumor is likely to be due to an aberrant expression control system of the cell, rather than a change in the control region of the gastrin gene.

Topics: Amino Acid Sequence; Base Sequence; Chromosome Mapping; DNA Restriction Enzymes; DNA, Neoplasm; Gastrins; Gene Expression Regulation; Humans; RNA, Messenger; Stomach; Transcription, Genetic; Zollinger-Ellison Syndrome

Hypergastrinemia and gastric acid hypersecretion are the principal laboratory features of Zollinger-Ellison syndrome. Decision and cost-effectiveness analyses were employed in the present study to compare and contrast the diagnostic strategies of initial gastric analysis followed by secretin infusion test versus secretin infusion test alone in the evaluation of hypergastrinemia in patients suspected of having gastrinoma. The results of this study showed that 59 percent of patients with elevated serum gastrin values were either hypochlorhydric or achlorhydric. Application of decision analysis to either diagnostic strategy demonstrated that gastric analysis followed by secretin infusion test, if indicated, was superior in expected value than secretin infusion test alone. Likewise, in this group of patients, performance of gastric analysis in the outpatient setting prior to secretin infusion testing was financially more advantageous than performance of secretin infusion testing alone. These results also demonstrate the importance of performing gastric analysis prior to anticipated hospitalization for evaluation of suspected gastrinoma. Such testing would obviate unnecessary hospitalization and medical costs.

Topics: Adolescent; Adult; Aged; Cost-Benefit Analysis; Decision Making; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

As effective tumour resection can be achieved in only a minority of patients with Zollinger-Ellison syndrome, therapy in such patients is usually directed to treatment and prevention of symptoms induced by hypersecretion of gastric acid. Omeprazole is a potent and long-acting inhibitor of pentagastrin stimulated gastric acid secretion in normal subjects, and this prompted a study of the effect of omeprazole on gastric acid hypersecretion and acid peptic disease resulting from endogenous hypergastrinaemia in Zollinger-Ellison patients. Omeprazole was found to be effective even in those patients whose symptoms were not adequately controlled by high doses of histamine H2-receptor antagonists, with or without pirenzepine. Serum gastrin levels were not affected; no laboratory abnormalities and minimal side-effects induced by omeprazole have been reported in Zollinger-Ellison patients even on long-term studies of up to 27 months.

Topics: Anti-Ulcer Agents; Benzimidazoles; Gastric Acid; Gastrins; Humans; Omeprazole; Peptic Ulcer; Time Factors; Zollinger-Ellison Syndrome

We have already shown that gastrinomas release gastrin when stimulated with secretin in vitro. In order to ascertain whether this is true in vivo and whether the reaction is clinically useful in the localization of gastrinomas, secretin was injected into a feeding artery of the gastrinoma in four patients, and blood samples were taken from a peripheral artery (PA) and the hepatic vein (HV) for determination of immunoreactive gastrin (IRG) and immunoreactive insulin (IRI) levels. When secretin was injected into a feeding artery of the gastrinoma, IRG rose within 40 seconds in the HV and within 60 seconds in the PA. When secretin was injected into a nonfeeder, IRG did not rise for 2 min in the PA. This test was performed to two of the postgastrectomized patients and a patient with hypergastrinemia due to atrophic gastritis. In these patients, IRG in the hepatic vein did not rise for two minutes. It was concluded that secretin directly stimulates gastrinomas to release gastrin in vivo and that the selective arterial secretin injection test is helpful in determining the location of the gastrinoma.

Topics: Adult; Aged; Female; Gastrins; Hepatic Veins; Humans; Injections, Intra-Arterial; Insulin; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

In 1982, a prospective study was initiated of 52 consecutive patients with proven Zollinger-Ellison syndrome (ZES), involving surgical exploration with the goal of removing the gastrinoma after an extensive protocol to localize the tumor. Each patient underwent ultrasound, computed tomography (CT) with oral/intravenous (IV) contrast, and selective arteriography. Eighteen patients had metastatic disease identified by imaging studies and confirmed by percutaneous biopsies, and two patients had multiple endocrine neoplasia type I (MEN-I) with negative imaging studies; therefore, these 20 patients did not undergo laparotomy. Each of the remaining 32 patients (3 with MEN-I and positive imaging studies) underwent laparotomy, and gastrinomas were removed in 20 patients. Preoperative ultrasound localized tumors in 20% of patients, CT in 40%, arteriography in 60%, and any of the modalities in 70% of patients. Infusion CT and arteriography were 100% specific. In 18 patients with either negative imaging (17) or false-positive imaging (1 ultrasound), gastrinomas were found and removed in six patients (33%). Twenty-four gastrinomas were found in 20 patients at laparotomy: eight in lymph nodes around the pancreatic head, four in the pancreatic head, one in the pancreatic body, three in the pancreatic tail, three in the pyloric channel, one in the duodenal wall, two in the jejunum at the ligament of Treitz, one in the ovary, and multiple liver metastases in one patient. If one excludes patients with MEN-I or liver metastatic disease, 12/28 (43%) of patients were biochemically "cured" immediately after operation. This result decreased to 7/23 (30%) with greater than 6 months follow-up. No patients with gastrinomas resected have developed recurrent gastrinoma on follow-up imaging studies (longest follow-up: 4 years). This study indicates that 95% of metastatic gastrinoma can be diagnosed before operation and that, by a combination of careful imaging studies and thorough exploration at surgery, 30% of patients with gastrinomas may be curable.

Topics: Adult; Aged; Female; Follow-Up Studies; Gastric Acid; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Prospective Studies; Tomography, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

In 27 consecutive patients with Zollinger-Ellison syndrome, we prospectively evaluated the ability of selective venous sampling for gastrin to localize gastrinomas, then compared the results with those from imaging studies and with findings at surgery. All patients had a gastrin gradient, but in only 20 patients was it significant. Neither the magnitude of the gastrin gradient nor its presence or absence correlated with the frequency with which gastrinoma was found at surgery. A gastrinoma was found at surgery in 15 patients, of whom 12 had positive imaging studies, 11 had a significant gastrin gradient, 14 had both tests positive, and 1 had both tests negative. A gastrinoma was not found at surgery in 12 patients, of whom 8 had a significant gradient and none had a positive imaging study. Gastrin sampling has equal sensitivity with imaging studies in localizing gastrinoma, but imaging studies have higher positive and negative predictive values and higher specificity. Thus, selective venous sampling for gastrin is much less useful in localizing gastrinoma than has been suggested and should not be routinely done preoperatively in patients with Zollinger-Ellison syndrome.

Topics: Adult; Aged; Angiography; Blood Specimen Collection; Female; Gastrins; Humans; Laparotomy; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Tomography, X-Ray Computed; Ultrasonography; Veins; Zollinger-Ellison Syndrome

A case of a young female patient affected by Zollinger-Ellison syndrome with occult gastrinoma during exploratory laparotomy, is reported. On the basis of transhepatic portal catheterization the patient underwent pylorus preserving pancreatoduodenectomy according to Longmire-Traverso. A malignant gastrinoma of the duodenal wall, 2 mm in diameter, was observed on the operative specimen in the suspected gastrinogenic area. The procedure led to complete clinical recovery of the patient who did not respond to the medical treatment of the ulcer. The prognosis was good with oncologic radicality of surgery confirmed at follow-up and excellent digestive function.

Topics: Adult; Drug Therapy, Combination; Duodenum; Female; Gastrins; Humans; Pancreas; Pirenzepine; Ranitidine; Zollinger-Ellison Syndrome

A patient with documented metastatic islet cell carcinoma of the pancreas and Zollinger-Ellison syndrome, with regression of tumor after total gastrectomy is described. Pertinent similar cases are summarized further suggesting that gastrectomy may have a role in the management of the tumorous as well as the acid-secretory features of this disease.

Topics: Aged; Female; Gastrectomy; Gastrins; Humans; Pancreatic Neoplasms; Postoperative Period; Zollinger-Ellison Syndrome

A 45-min gastrin assay with a minimum detection limit of 50 pg/ml plasma has been developed which makes use of delayed addition of labeled tracer. The precision of the rapid assay compares favorably with standard methods for measurement of plasma gastrin concentrations in excess of 100 pg/ml. The rapid method can be used for emergency preoperative diagnosis of Zollinger-Ellison syndrome and as an aid in localizing gastrinomas before or during surgery.

Topics: Fasting; Gastrins; Humans; Hyperparathyroidism; Radioimmunoassay; Time Factors; Zollinger-Ellison Syndrome

In Zollinger-Ellison syndrome (ZES), the discovery of gastrinomas in unusual locations, such as a lymph node, poses a diagnostic problem centered on whether the neoplasm is primary or metastatic. The clinical, gross, microscopic, immunocytochemical, and ultrastructural features of ectopic gastrinomas were studied in four patients with ZES, and reports of 14 similar cases were reviewed. These extragastroenteropancreatic (EGEP) gastrinomas have many of the morphologic features of gastrinomas in conventional locations. However, the centrifugal expansile growth pattern, characterized by a thick fibrous capsule, hyalinized fibrous septa, and, frequently, cystic degenerative changes in EGEP gastrinomas should alert the pathologist to the probability that these neoplasms are primary. Additional evidence for the primary nature of these EGEP gastrinomas is derived from the postoperative normalization of high serum gastrin levels and the correction of the abnormal gastrin response to secretin challenge or to calcium infusion tests. Increased awareness of the occurrence and features of these EGEP gastrinomas is crucial for both pathologists and surgeons to ensure proper evaluation and treatment of patients with ZES.

Topics: Adolescent; Adult; Gastrins; Histocytochemistry; Humans; Immunochemistry; Male; Microscopy, Electron; Middle Aged; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Although there are multiple etiologies of clinical hypergastrinemia, the most important cause is gastrinoma [Zollinger-Ellison (ZE) syndrome]. The most significant advance in the management of patients with the ZE syndrome has been the development of the ability to establish firmly the correct preoperative diagnosis by radioimmunoassay. We believe that all patients who have the ZE syndrome should undergo operation for two reasons: to identify and resect all tumor and because in patients in whom no tumor is found or in whom all tumor cannot be resected, the most reliable relief of hypersecretory symptoms for the life of the patient can be achieved by total gastrectomy.

Topics: Cimetidine; Diagnosis, Differential; Female; Gastrectomy; Gastric Juice; Gastrins; Male; Methods; Ranitidine; Stomach Diseases; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Male; Microscopy, Electron; Middle Aged; Pancreas; Pancreatic Neoplasms; Postoperative Complications; Zollinger-Ellison Syndrome

In order to evaluate the clinical requirement for gastrin measurements, we examined all gastrin measurements requested over 1.5 years in a homogeneous population of 5.1 million inhabitants. Gastrin was quantitated with a radioimmunoassay that measured bioactive gastrins with equimolar potency. We received 1392 serum samples from 931 patients. In 394 samples from 121 patients the gastrin concentration was above the limit of the reference interval (50 pmol/l). Of the 121 patients, 19 were known Zollinger-Ellison patients followed for control of the therapy. In 11 previously unknown patients the gastrin analysis suggested presence of gastrin-producing tumours. Of these, four had classical Zollinger-Ellison syndromes, three had mixed endocrine tumours without peptic ulcer, and four were awaiting final confirmation of gastrinomas. Two vitiligo patients were hypergastrinaemic suggesting latent pernicious anaemia. Upon second measurement the plasma gastrin concentrations were within the reference interval in 14 previously hypergastrinaemic ulcer patients. In the remaining 75 patients the hypergastrinaemia was secondary to other gastrointestinal diseases. The results indicate that diagnosis, localization, and therapeutic control of gastrinomas require 200 gastrin measurements per million inhabitants per year. We suggest that this number be used in planning gastrin-assay services.

Topics: Blood Specimen Collection; Endocrine System Diseases; Gastrins; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Humans; Neoplasms; Radioimmunoassay; Zollinger-Ellison Syndrome

Recent studies on the gene sequence encoding the human pyloric antral hormone, gastrin, indicate a precursor of 101 residues. We have now raised antibodies to a synthetic analogue corresponding to (Tyr)-human progastrin COOH-terminal pentapeptide. The antibodies could be used in radioimmunoassay to measure this peptide, but they did not react with corresponding fragments of procholecystokinin, porcine progastrin, or other human progastrin-derived peptides, notably heptadecapeptide gastrin (G17), and 34-residue gastrin (G34). Radioimmunoassay of human antral and duodenal extracts revealed a major peak of activity that corresponded to the native COOH-terminal fragment of progastrin, and occurred in approximately equimolar amounts with COOH-terminal G17 immunoreactivity. In addition, there was a minor peak of apparently higher molecular weight material. In some gastrinomas the latter material was the predominant immunoreactive form, and it occurred in higher molar concentrations than any other form of gastrin. Digestion of this material with trypsin liberated peptides that reacted with antibodies specific for the NH2-terminus of G34, and G17. On this basis the high molecular weight component was identified as a form of gastrin that extended from the COOH-terminus of the precursor to a point at least beyond the NH2-terminus of G34, and probably included the entire progastrin sequence. The results suggest differences in posttranslational processing pathways of progastrin in antrum, duodenum, and gastrinomas. They also indicate that the present experimental approach allows the identification of progastrin-like substances, which should open the way to studying the mechanisms of gastrin biosynthesis.

Topics: Chromatography, High Pressure Liquid; Duodenum; Gastric Mucosa; Gastrins; Humans; Peptide Fragments; Protein Precursors; Pyloric Antrum; Radioimmunoassay; Trypsin; Zollinger-Ellison Syndrome

Topics: Gastric Juice; Gastrins; Humans; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Middle Aged; Protein Precursors; Radioimmunoassay; Zollinger-Ellison Syndrome

Secretin appears to have a direct effect on gastrinoma cells, which results in a paradoxic increase in the serum gastrin level in patients with the Zollinger-Ellison syndrome. To evaluate this effect, gastrinoma cells were challenged with secretin in acute cell dispersion or after 2 weeks in culture. Acutely dispersed cells were incubated for 15 minutes or 3 hours with and without secretin 10(-6) mol/L. (sec). There was no significant difference in gastrin release between control and sec groups in the two acute incubation periods. At 15 minutes the control value was 47 +/- 1 and the sec value was 54 +/- 1 ng/ml, while at 3 hours the control value was 59 +/- 1 and the sec value was 61 +/- 1 ng/ml. In the cell culture preparation, secretin stimulated gastrin release at all doses (control 463 +/- 85, SEC 10(-10) mol/L 603 +/- 37, sec 10(-8) mol/L 706 +/- 37, sec 10(-6) mol/L 798 +/- 48 pg/ml ([p less than 0.05, Student t test]). These results indicate that secretin stimulates gastrin release directly from cultured gastrinoma cells in a dose-dependent manner but does not stimulate gastrin release from acute cell dispersion. This might be attributed partly to the recovery of secretin receptors in the cultured cells.

Topics: Cells, Cultured; Dose-Response Relationship, Drug; Gastrins; Humans; Male; Middle Aged; Secretin; Time Factors; Zollinger-Ellison Syndrome

We have investigated the gastric endocrine cells in 19 patients with the Zollinger-Ellison syndrome. Six received a long-term treatment with omeprazole, 5 one with H2 receptor antagonists and 8 had no medical treatment. Fifteen patients (79%) had hyperplasia of the endocrine cells in the oxyntic mucosa independent of treatment. The hyperplasia involved both enterochromaffin-like (ECL) and D1 cells and was positively related to the duration of disease (p less than 0.05). The duration of hypergastrinaemia was longer in the omeprazole-treated patients, but the hyperplasia was not significantly more pronounced in these patients. Gastric carcinoid tumours consisting mainly of ECL cells are rare in man and are most often seen in states of hypergastrinaemia such as chronic atrophic gastritis. It has seldomly been reported in Zollinger-Ellison patients; but now, when potent antisecretory drugs make it possible to avoid total gastrectomy, a raised incidence might result, and an increased attention to this aspect seems appropriate.

Topics: Female; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Male; Omeprazole; Time Factors; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Injections, Intra-Arterial; Secretin; Zollinger-Ellison Syndrome

A 37-year-old man with a primary mesenteric gastrinoma is reported. A parathyroid adenoma had been removed 13 years ago. Six years earlier the patient underwent an emergency distal gastrectomy because of massive bleeding from a duodenal ulcer. Two months later stomal ulcers developed associated with hypergastrinemia. No gastrinoma was detected and total gastrectomy was performed. The fasting plasma level of gastrin was stable in the range from 580 to 920 pg/ml for the following 5 years. However, the level was found to abruptly increase to 4125 pg/ml. The level increased progressively to 11383 pg/ml within 1 year. A gastrinoma was identified in the jejunal mesenterium, and it was completely removed. After surgery the plasma level of gastrin decreased below the limit of the assay, and the paradoxical response to secretin was no longer observed.

Topics: Adult; Gastrins; Humans; Laparotomy; Male; Mesenteric Arteries; Mesentery; Peritoneal Neoplasms; Radiography; Zollinger-Ellison Syndrome

Using fragment 5-17 of human gastrin-17 extended with glycine at the C-terminus as hapten, three of six rabbits produced high-titer, high-avidity antisera specific for glycine-extended gastrins. In combination with trypsin and carboxypeptidase B cleavage, radioimmunoassays based on these antisera measured progastrins in some extra-antral tissues and certain malignant tumors. The results show that sequential cleavage with trypsin and carboxypeptidase B followed by radioimmunoassay of glycine-extended peptides is a rapid and accurate procedure for measurement of biosynthetic precursors of alpha-amidated peptide hormones. Moreover, the procedure seems promising in the search for tumor markers.

Topics: Animals; Carboxypeptidase B; Carboxypeptidases; Cholecystokinin; Chromatography, Gel; Chromatography, Ion Exchange; Gastrins; Glycine; Hormones; Humans; Hydrolysis; Protein Precursors; Radioimmunoassay; Swine; Trypsin; Zollinger-Ellison Syndrome

There have been new developments in the diagnosis and therapy of Zollinger-Ellison syndrome. The main symptoms of the syndrome are ulcers at atypical sites and nocturnal hypersecretion. Diarrhea and steathorrhea are equally common and may be misinterpreted. Diagnosis is established by the paradoxical rise in plasma gastrin after intravenous secretin provocation. Fasting plasma gastrin levels alone may be misleading and suffer from both false positive and false negative results. Previously, total gastrectomy was necessary to prevent complications. Today the symptoms can be controlled by adequate H2-receptor blocker treatment, if necessary combined with an antimuscarinic drug such as pirenzepine. Exploratory surgical attempts to remove the tumor have a success rate of only 20% and only half of those may be cured. However, the new technique of transhepatic pancreatic vein catheterization, supplemented by determination of local hormone gradients, allows preoperative localization of even small tumors. In the last two years the author has had experience of 5 patients with endocrine tumors of the pancreas (1 insulinoma, 4 gastrinoma) who underwent this procedure. In every case the tumor was localized, removed by surgery and the patients subsequently cured of the syndrome, even including 2 patients with multiple endocrine neoplasia (MEN 1). It is concluded that this chance of cure should be offered to every patient with this syndrome.

Topics: Combined Modality Therapy; Female; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Male; Multiple Endocrine Neoplasia; Palliative Care; Secretin; Zollinger-Ellison Syndrome

Results of preparathyroidectomy and postparathyroidectomy studies in a patient with multiple endocrine neoplasia type I and gastrinoma suggest that hyperparathyroidism unmasks occult gastrinoma and related secretory abnormalities. Three of four diagnostic findings were later obscured by parathyroidectomy and normalization of serum calcium concentration. Basal acid output, basal acid output/maximal acid output ratio, and serum gastrin concentration were decreased from values consistent with gastrinoma to normal. The secretin stimulation test, though still positive, was attenuated. These observations suggest that in multiple endocrine neoplasia type I, normal values for serum gastrin concentration, gastric secretion, and secretin stimulation may not exclude gastrinoma. The investigations clarify the interpretation of a voluminous but confusing literature on the interrelationship between hyperparathyroidism and altered gastric function in the presence or absence of Zollinger-Ellison syndrome.

Topics: Adenoma; Adult; Calcium; Drug Interactions; Female; Gastric Acid; Gastrins; Humans; Hyperparathyroidism; Multiple Endocrine Neoplasia; Parathyroid Hormone; Pituitary Neoplasms; Secretin; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Twenty-two patients with Zollinger-Ellison syndrome were managed by a combined medical and surgical approach. Patients were treated initially with cimetidine or ranitidine. A laparotomy was performed to remove easily resectable tumors and to carry out a proximal gastric vagotomy. Tumors were found in 9 patients (41%) and all visible tumors were removed from 6 of the 9 patients. Fasting serum gastrin concentrations and serum gastrin responses to intravenous secretin were normal 6 wk after surgery in each of the patients from whom all visible tumors were resected and are normal in 4 patients, 6 wk to 5 yr after surgery. Acid secretion was reduced after vagotomy in each patient, even when tumors were not found or completely resected. Thus, vagotomy decreased the acid secretory response to endogenous hypergastrinemia. In addition, vagotomy augmented the inhibitory effect of H2-receptor antagonists on acid secretion. Follow-up has ranged from 6 wk to 6 yr (median, 2 yr). Dosages of cimetidine or ranitidine have been reduced, compared with preoperative amounts, in all but 1 patient. Two patients are taking no antisecretory drugs. Only 3 patients have had occasional symptoms of ulcer disease. Complications such as bleeding, perforation, or obstruction have not occurred in any patient. Endoscopy was performed in all patients to estimate the point prevalence of active ulcers and an ulcer was found in 1 patient. Based on these results, it is our opinion that this combined medical and surgical approach is an effective treatment for patients with Zollinger-Ellison syndrome.

Topics: Adolescent; Adult; Child; Cimetidine; Combined Modality Therapy; Endoscopy; Female; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Laparotomy; Male; Middle Aged; Prospective Studies; Ranitidine; Vagotomy; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

In eight of 10 patients with Zollinger-Ellison syndrome resection of all visible tumor tissue was combined with gastrectomy. The results in this group of patients, as in other series reported in the literature, suggest that excision of gastrinoma by partial pancreatectomy or enucleation can be combined safely with gastrectomy. Perhaps excision of tumor is preferable in the management of patients with solitary tumor who do not have the multiple endocrine neoplasia syndrome. We await further follow-up studies and experience with additional patients before judging this thesis of tumor resection with gastric preservation.

Topics: Adenoma; Adult; Aged; Carcinoma; Female; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatectomy; Zollinger-Ellison Syndrome

A patient with a calcifying chronic pancreatitis was found to have a neuroendocrine islet cell tumour (a previously unreported association). The tumour secreted both gastrin and ACTH leading to clinical manifestations of both the Zollinger-Ellison syndrome and Cushing's syndrome.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Aged; Calcinosis; Chronic Disease; Gastrins; Humans; Male; Pancreatic Neoplasms; Pancreatitis; Zollinger-Ellison Syndrome

The case history of a patient with an islet cell carcinoma, which produced both gastrin and vasoactive intestinal polypeptide (VIP), is presented. Although several examples have been observed of the combined production of these hormones by pancreatic endocrine tumors, few reports have related the clinical details of such cases. Resolution of diarrhea occurred in our patient after institution of nasogastric suction and cimetidine therapy, suggesting that gastric hypersecretion, rather than VIP activity, accounted for this problem. Chemotherapy with streptozotocin and 5-fluorouracil was highly effective in ameliorating clinical symptoms, diminishing serum levels of gastrin and VIP, and greatly reducing the bulk of metastatic disease in this case.

Topics: Adenoma, Islet Cell; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Gastrins; Humans; Middle Aged; Pancreatic Neoplasms; Streptozocin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Dacarbazine; Gastrins; Glucagon; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Child; Female; Gastrins; Humans; Zollinger-Ellison Syndrome

A method is described that uses the avidin-biotin complex (ABC) immunoperoxidase technique to provide a rapid, sensitive, and specific means to quantitate isolated G cells in cultures and suspensions.

Topics: Animals; Avidin; Biotin; Cells, Cultured; Fixatives; Gastric Mucosa; Gastrins; Humans; Immunoenzyme Techniques; Male; Pyloric Antrum; Rats; Rats, Inbred Strains; Zollinger-Ellison Syndrome

Localisation of C-terminal gastrin immunoreactivity has been studied, using the immunogold staining procedure, on ultrathin sections of 6 human gastrinomas conventionally processed for electron microscopy. The specific labelling, whose density depended on the mean diameter of the gold marker, was restricted to endocrine secretory granules. However, in poorly differentiated cells from malignant tumours, a number of granules remained unreactive. The labelling pattern depended also on the functional state of each cell. The immunoreactive granules showed various morphological features. A moderate number of gold particles was demonstrated over the floccular content of the infrequent diagnostic G-type granules. Non-diagnostic round granules of varying size and electron density were prevalent in most cells; their usually strong immunostaining allowed immediate recognition of cell specificity. Dense granules which were large in size and angular in shape and present in one case, were also intensely labelled. In the same tumour, unequal labelling occurred over polymorphous, often elongated granules, of varying size. Granules of different types, including intermediate forms, could be found in the same cell, indicating a spectrum of granule maturation towards well-defined types of the fetal or adult normal tissues. The present methodology would help to identify gastrin-producing cells in prospective or retrospective electron microscopy studies of multi-hormonal endocrine tumours.

Topics: Adult; Cytoplasmic Granules; Endocrine System Diseases; Female; Gastrins; Gold; Humans; Immunologic Techniques; Male; Microscopy, Electron; Middle Aged; Neoplasms; Zollinger-Ellison Syndrome

Dispersed single-cell suspensions of human gastrinoma tissue were incubated for 15, 60, and 120 min in a calcium-containing medium, (0.1, 2, 10 mM) in calcium-free medium and in calcium-free medium containing the calcium ionophore A23187 (0.01, 1, and 100 micrograms/ml). Supernatant and pellet (intracellular) gastrin levels were determined by radioimmunoassay. Supernatant gastrin levels remained stable over 120 min in calcium chloride or calcium gluconate containing medium, while intracellular pellet gastrin approximately tripled during the same incubation period. Total gastrin (supernatant plus pellet) approximately doubled during the 2-hr incubation in calcium. However, calcium (0.1, 2, or 10 mM) failed to produce a dose-dependent rise in supernatant, pellet, or total gastrin when compared to calcium-free incubates. Contrary to the expected gastrin response to calcium, supernatant and pellet gastrin levels were higher in incubates in calcium-free medium than in calcium-containing incubates. A23187 (0.01 or 1 mcg/ml) in a calcium-free medium decrease supernatant gastrin while high dose ionophore (100 mcg/ml) increased supernatant gastrin. All doses of ionophore stimulated pellet and total gastrin levels. Thus, it appears that the clinical augmentation of gastrin levels, seen with calcium challenge in vivo may not be solely due to changes in serum calcium.

Topics: Adult; Calcimycin; Calcium; Cytological Techniques; Gastrins; Humans; Male; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adolescent; Diagnosis, Differential; Duodenal Diseases; Duodenal Ulcer; False Positive Reactions; Female; Gastrins; Gastroesophageal Reflux; Humans; Pain; Stomach Diseases; Zollinger-Ellison Syndrome

We examined the specificity of commercially available antibodies used in measurement of serum gastrin. Antibodies were obtained from five commercial laboratories, and antibody immunoreactivity with gastrin and cross-reactivity with cholecystokinin (CCK) were determined. All antibodies were equally immunoreactive with gastrin, and cross-reactivity of three antibodies with CCK was minimal (less than 5%). In contrast, substantial cross-reactivity with CCK was found with two antibodies. To determine the clinical significance of cross-reactivity with CCK, secretin injection tests were performed in 24 individuals: seven in normal health, four with Zollinger-Ellison syndrome, three with antral gastrin cell hyperfunction, six with ordinary duodenal ulcer disease, and four with atrophic gastritis. Serum gastrin levels were measured with all five gastrin antibodies. The response to secretin was negative in all normal subjects and in those with duodenal ulcer and antral gastrin cell hyperfunction. The response to secretin was positive in all four patients with gastrinoma with use of the five antisera. All four patients with atrophic gastritis had normal responses to secretin when antibodies with minimal CCK cross-reactivity were used; however, two of four had false positive secretin test results when serum gastrin levels were measured with the two antibodies with a high degree of cross-reactivity with CCK. These studies indicate that significant cross-reactivity of gastrin antibodies with CCK can result in false positive secretin injection test results and can lead potentially to the erroneous diagnosis of Zollinger-Ellison syndrome.

Topics: Antibodies; Cholecystokinin; Cross Reactions; False Positive Reactions; Gastrins; Gastrointestinal Diseases; Humans; Injections, Intravenous; Radioimmunoassay; Secretin; Structure-Activity Relationship; Zollinger-Ellison Syndrome

Topics: Calcium; Duodenal Ulcer; Fasting; Gastrins; Glucagon; Humans; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Chlorides; Diagnostic Errors; Duodenal Ulcer; Female; Gastrins; Humans; Water-Electrolyte Imbalance; Zollinger-Ellison Syndrome

The article describes 44 observations of peptic ulcers, the appearance of them being explained by the retained antral mucosa in the stump of the duodenum and stomach.

Topics: Calcium; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Peptic Ulcer; Postoperative Complications; Secretin; Zollinger-Ellison Syndrome

In vitro studies have demonstrated that secretin can stimulate the release of parathyroid hormone (PTH), but reports concerning its effects on PTH and calcium in vivo are contradictory. To examine this question further, a bolus injection of secretin (75 IU) was given to 12 normal subjects and 10 patients with primary hyperparathyroidism (HPT). Six of the patients had multiple endocrine neoplasia and five had endocrine pancreatic tumours (EPT). Three normocalcaemic patients with EPT were also included in the study. The mean serum gastrin level rose significantly (from 19 to 40 pmol/l, p less than 0.01) within 15 min of secretin injection in the normal subjects. HPT patients without EPT had a somewhat higher mean basal level of gastrin (39 pmol/l, p less than 0.05 compared with controls), but it did not increase significantly after the secretin bolus. In six EPT patients the gastrin concentrations rose by more than 300 pmol/l. Although secretin had a biological capacity to release gastrin, it had no discernible effects on either serum PTH or serum calcium in any of the groups studied. Nor were any changes in PTH or calcium observed when secretin was given as a continuous infusion (3 IU/kg/h) over 90 min. Thus, our data do not support the concept that secretin, in vivo, is a secretagogue of PTH.

Topics: Adult; Aged; Calcium; Female; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Parathyroid Glands; Parathyroid Hormone; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Calcium; Female; Gastrins; Humans; Infusions, Parenteral; Injections, Intravenous; Iodine; Male; Middle Aged; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Gastrins; Humans; Male; Neoplasms, Multiple Primary; Pancreas; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

A 63-year-old man with a 2-year history of upper gastrointestinal ulcers was found to have the Zollinger-Ellison syndrome. Despite histologic verification of gastrinoma, several fasting serum gastrin concentrations were normal. However, in response to intravenous secretin infusion, a paradoxical increase in serum gastrin levels indicative of gastrinoma was seen. Although serum gastrin concentrations in patients with suspected gastrinoma may be persistently normal, provocative testing may be necessary to establish the diagnosis of the Zollinger-Ellison syndrome.

Topics: Fasting; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Cystadenoma; Female; Gastrins; Humans; Ovarian Neoplasms; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Diagnostic Errors; Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

A patient with the Zollinger-Ellison syndrome was followed with multiple gastric secretion tests and serum gastrin analyses for six years. During this period cimetidine requirement increased to a daily dose of 8 g, but it reversed spontaneously after two years. The altered cimetidine effectiveness was not associated with reduced oral bioavailability and serum calcium was unchanged. Total serum gastrin was very high at all times, and fractionation of gastrins in serum by gel filtration showed varying proportion of big to small gastrins, but not in a mode which explained the parietal cell resistance to cimetidine.

Topics: Adult; Cimetidine; Drug Resistance; Female; Gastric Acid; Gastrins; Humans; Time Factors; Zollinger-Ellison Syndrome

From 1978 to 1984, six patients (four men and two women) with functioning extrapancreatic gastrinomas were treated at the University of Michigan Medical Center. In all but one patient, who was known to have a liver metastasis, selective portal and peripheral venous sampling was performed to localize the site(s) of increased gastrin levels. Serum levels of carboxy (C) and amino (N) terminal gastrin moieties were measured before surgery with region-specific antisera and N/C ratios were calculated. All patients underwent operative exploration and successful resection of all gastrinomas present including a single large liver metastasis in one case. The C-terminal gastrin level was elevated in all cases and the N/C ratios were well below 1.0 (greater than 1 is consistent with malignancy and metastases) in all but the one patient with a liver metastasis. All patients have remained clinically free of tumor and have had normal basal and secretin-stimulated gastrin levels for as long as 5 years after operation. Three of the patients had undergone previous total gastrectomies and had done well apart from persistent hypergastrinemia before resection of the tumor. Two patients have not undergone any type of gastric operation. Appropriately selected patients with Zollinger-Ellison syndrome, particularly those with extrapancreatic primary lesions, may be candidates for a curative resection.

Topics: Adult; Angiography; Female; Gastrins; Humans; Jejunal Neoplasms; Liver Neoplasms; Lymph Nodes; Male; Middle Aged; Peptide Fragments; Pyloric Antrum; Secretin; Stomach Neoplasms; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Gastrin- 17 (G-17) and gastrin-34-like immunoreactivities of human gastrinoma cells were investigated at light and electron microscope level using N-terminally directed antisera. The procedure includes (a) the 24 hr/immunoperoxidase staining of Bouin-fixed paraffin embedded tissues, (b) the immunoelectron microscopic labelling of aldehyde-fixed Epon-embedded tissues according to the immunogold technique. On light microscopy, a variable number of tumor cells stained for G-34. In contrast, G-17 immunoreactivity was very low or undetectable in the tumor material, although it was easily detected in endocrine cells of similarly processed human pyloric mucosa. On electron microscopy, most of the tumor cell granules belonging to the round compact or dense-cored type exhibited a variable labelling for G-34, whereas the vacuolar/floccular type remained unlabelled. In contrast, the labelling for G-17 occurred over most of the tumor cell granules, whether compact or floccular. Dense granules of varying size and shape, previously shown to store C-terminal gastrin immunoreactivity, were only faintly labelled by the two antisera. When compared to the labelling pattern of human pyloric G-cells, the predominance of round dense granules with G-34 and G-17 immunoreactivity in gastrinoma cells suggests an incomplete or defective post-translational processing of the precursor peptide.

Topics: Colloids; Gastrins; Gold; Humans; Immune Sera; Immunoassay; Immunoglobulin G; Microscopy; Microscopy, Electron; Protein Precursors; Zollinger-Ellison Syndrome

A young woman with acromegaly and Zollinger-Ellison syndrome associated with a GH-releasing factor (GRF)- and gastrin-secreting metastatic islet cell carcinoma was studied by means of specific antisera which recognize various regions of the GRF molecule. Using specific immunohistochemical techniques, the tumor cells were shown to contain GRF, gastrin, and gastrin-releasing peptide, but not GH. During a 4-h period, plasma GRF levels averaged 5.6 +/- 1.4 ng/ml (+/- SD), while GH levels averaged 148 +/- 71 ng/ml. GH secretion was pulsatile and increased after TRH administration. GRF RIAs may be useful in establishing the diagnosis of acromegaly secondary to the ectopic secretion of GRF.

Topics: Acromegaly; Adenoma, Islet Cell; Adult; Female; Gastrins; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

It has been hypothesized that secretin may act directly on gastrinoma through the adenylate cyclase system to cause stimulation of gastrin release. We studied gastrinoma cells in vitro to determine whether secretin would stimulate gastrin release directly and whether the gastrinoma cell membrane had a functional secretin receptor adenylate cyclase system. Fresh tumor was prepared in cell suspensions containing 1.5 X 10(6) viable cells and incubated for 2 hours with either 2 mM CaCl2 alone (control) or 2 mM CaCL2 and 0.025 U/ml secretin. The gastrin content of the cells in each incubation chamber and the medium were determined by radioimmunoassay and results were expressed as mean gastrin pg/microgram protein +/- SD. Under basal conditions the cellular gastrin content was 39.9 +/- 6.4 (control) compared with 16.7 +/- 2.1 (secretin). After 2 hours of incubation, cellular gastrin content increased in both groups: 68.5 +/- 11.9 (control) to 68.3 +/- 5.5 (secretin). However, the percent of gastrin released into the medium during incubation decreased by one half in both groups (control 37.3% +/- 4.0% to 22.2% +/- 3.0%; secretin 42.8% +/- 7.0% to 18.9% +/- 1.8%). Adenylate cyclase activity was assessed by measuring cAMP generation in fresh-frozen gastrinoma and cultured gastrinoma cell membranes. Isoproterenol (10(-5) M), PGE1 (10(-4) M), and GppNHp (guanine nucleotide) (10(-5) M) caused fivefold to 25-fold increases in cAMP generation. Secretin did not stimulate adenylate cyclase activity above basal (21.73 +/- 4.07 and 2.29 +/- 1.2 pmol cAMP/mg protein/min) for frozen and cultured gastrinoma, respectively. Secretin failed to stimulate gastrin release and adenylate cyclase in vitro. This suggests that secretin-stimulated gastrin release in vivo may not be due to a direct effect of secretin on the gastrinoma.

Topics: Adenylyl Cyclases; Animals; Cell Membrane; Cells, Cultured; Gastrins; Guinea Pigs; Humans; In Vitro Techniques; Pancreas; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Gastrointestinal Hormone; Secretin; Zollinger-Ellison Syndrome

37 patients suffering from apudomas of the pancreas are reported (18 insulinomas, 6 isletcell-hyperplasias, 9 Zollinger-Ellison syndroms, 1 glucagonoma, 3 without hormone production). In preoperative localization computerized tomography and angiography were the best with 65% positive findings. Insulinomas were enucleated, all free of recidives. 50% of operated isletcell hyperplasias had a postoperative resisting hyperinsulinism. Either gastrectomy or tumour enucleation was performed in the Zollinger-Ellison syndrome. The five-years survival rate was 43%.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Female; Follow-Up Studies; Gastrectomy; Gastrins; Glucagon; Humans; Hyperplasia; Insulin; Insulinoma; Islets of Langerhans; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Stomach Neoplasms; Zollinger-Ellison Syndrome

The peptic ulcer disease associated with hypergastrinemia is very often a challenging problem of diagnosis and therapy. In absolute surgical emergency (haemorrhagic and perforative complications), the utilization of the most recently discovered anti-ulcer drugs appears to be extremely helpful; the prevention of incumbent complications can be accomplished, in fact, during the post-operative treatment and the "free time" so obtained can be used for an adequate differential diagnosis (gastrinoma-induced Zollinger-Ellison syndrome: antrum retained, G cells of the antrum hyperplastic, apud-tumours with hypersecretion). The "anti-H2 and anti-muscarinic" drugs (often in association) give the surgeon the possibility of an accurate diagnosis and the choice of the best surgical procedure (tumorectomy, DCP, gastrectomy). Even in elective surgery the prevention with anti-H2 drugs permits greater "safety margins" and an optimal follow-up study. The results of the surgical experience in the General Surgical Clinic of Pisa (18 cases of Z.E.'s) confirm the validity of the associated anti-ulcer therapy.

Topics: Cimetidine; Female; Gastrins; Histamine H2 Antagonists; Humans; Middle Aged; Ranitidine; Zollinger-Ellison Syndrome

Topics: Calcium; Catecholamines; Female; Gastrins; Humans; Male; Multiple Endocrine Neoplasia; Parathyroid Hormone; Prolactin; Time Factors; Zollinger-Ellison Syndrome

There are two distinct problems in patients with Zollinger-Ellison Syndrome (ZES): peptic ulcer diathesis and malignant tumors. Antisecretory drugs have allowed us to control the ulcer symptoms and acid output in 45 patients with ZES. We report here the initial seven patients selected for surgical exploration with the goal of removing their gastrinomas. Prior to surgery, an extensive and rigorous protocol to localize the gastrinoma was carried out, including hypotonic duodenography, abdominal ultrasonography, selective arteriography, portal vein sampling for gastrin, and computerized tomography. With this protocol of radiographic localization, gastrinomas were found in two of the seven cases and the syndrome was "cured" in three of the seven patients. The results also demonstrate that preoperative localization is not a substitute for careful surgical exploration as tumors were found in two patients in whom localization failed.

Topics: Adult; Angiography; Cimetidine; Duodenum; Endoscopy; Female; Gastric Acid; Gastrins; Humans; Liver; Male; Middle Aged; Multiple Endocrine Neoplasia; Preoperative Care; Radionuclide Imaging; Ranitidine; Spleen; Tomography, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

Diagnosis and management of Zollinger-Ellison syndrome (ZES) do not appear to be established even today. In the present study, 143 cases of ZES (including 12 of author's experience) were collected from Japanese literature and analyzed, and diagnosis and management were discussed. (1) Although 43% of patients showed high gastrin level (greater than or equal to 500pg/ml), it is worth to be stressed that gastrin level was below 300pg/ml in 29% of patients. (2) Secretin provocation test was essential for diagnosis and particularly useful for detecting ZES with low gastrin level. (3) Angiography and/or blood samplings of PTPC were widely used for localizing gastrinoma but the informations thus obtained were not always of help for complete removal of tumors since malignant or multiple gastrinomas were frequent. (4) An aim of management for ZES consists of complete removal of tumor but it is not always feasible. Therefore, removal of target organ (total gastrectomy) should be routinely added for long-term cure. (5) Value of chemical gastrectomy (H2-receptor antagonist) is still a matter of pros and cons but substantial value of this drug should be considered adjunct to surgery.

Topics: Gastrectomy; Gastrins; Histamine H2 Antagonists; Humans; Secretin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Female; Gastrins; Glucagon; Humans; Hyperplasia; Islets of Langerhans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Serotonin; Somatostatin; Staining and Labeling; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

The role of radioimmunoassay (RIA) in the diagnosis and management of endocrine tumors, such as pituitary tumors, insulinomas, and gastrinomas, has long been well established. A variety of nonendocrine tumors are capable of elaborating one or more humoral substances that resemble immunologically well-known, well-characterized biologically active hormones or their prohormone precursors or metabolic products. The possible value of mass screening for carcinoma of the lung by the detection of precursor adrenocorticotropic hormone (ACTH) in plasma was tested. However, the usefulness was limited by the potential for false-positive, i.e., elevation of marker concentration in the plasma of heavy smokers even in the absence of invasive carcinoma. Although on occasion a dramatic decrease of plasma ACTH after surgical resection or on some chemotherapeutic schedules has been observed, this does not occur with sufficient regularity to serve definitely as an objective measure of efficacy of therapy. The limitations of nonhormonal tumor markers, such as carcinoembryonic antigen (CEA), are also considered.

Topics: Adrenocorticotropic Hormone; Animals; Diagnosis, Differential; Endocrine System Diseases; Gastrins; Humans; Insulin; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Pituitary Neoplasms; Radioimmunoassay; Zollinger-Ellison Syndrome

In 3 patients with Zollinger-Ellison syndrome, gastric pepsin and acid secretion, and pepsin acid correlation were studied. The results obtained are as follows. In nocturnal secretion, and histamine-, insulin- and gastrin-stimulated secretion, pepsin hypersecretion was not as conspicuous as acid hypersecretion, and so pepsin acid correlation showed low levels of less than 1.0. Not only before operation but also after vagotomy or distal gastrectomy, the same results were obtained. These results suggest that both before and after operation Zollinger-Ellison syndrome should be suspected in patients with pepsin acid correlation of less than 1.0 in nocturnal secretion or stimulated secretion.

Topics: Adult; Circadian Rhythm; Female; Gastric Acid; Gastrins; Histamine; Humans; Insulin; Middle Aged; Pepsin A; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Calcium; Female; Gastrectomy; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Middle Aged; Motilin; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

An 8-year-old boy with persistent duodenal ulceration was found to have hypergastrinaemia due to a solitary hepatic gastrinoma. Surgical resection has been followed by total clinical remission for a period exceeding 2 years.

Topics: Child; Duodenal Ulcer; Gastrins; Humans; Liver Neoplasms; Male; Zollinger-Ellison Syndrome

The prevalence of hypergastrinemia was determined in 38 consecutive patients with proved primary hyperparathyroidism. Uncorrected serum calcium levels ranged from 2.6 to 4.0 mmol/L and parathyroid hormone levels from 260 to 8750 ng/L (normal less than 600 ng/L). Preoperative serum gastrin levels were grossly elevated (1000 to 4000 ng/L) in three patients (normal median 63 ng/L; range 30 to 120 ng/L). Two patients were achlorhydric. After parathyroidectomy (adenomatous hyperplasia) in the third patient, the serum gastrin level decreased from 4000 to 3000 ng/L, with a negative response to both a secretin challenge and a meal test. The latter patient was subsequently shown to have an adrenal ganglioneuroma and islet cell hyperplasia, neither containing gastrin, and at 4-year follow-up she still has no symptoms from the hypergastrinemia. Eight patients had a modest hypergastrinemia. Serum gastrin levels returned to normal in three of the four patients after parathyroidectomy. The fourth patient had rheumatoid arthritis, which can be associated with hypergastrinemia. The mean plasma gastrin level before operation (100.3 +/- 26.1 ng/L) was similar to the postoperative value (67.0 +/- 18.5 ng/L). There was no correlation between parathyroid hormone and gastrin levels nor between serum calcium and gastrin levels. The three patients with duodenal ulcers did not have elevated gastrin levels. Therefore it would appear that routine screening of patients with primary hyperparathyroidism adds little to their clinical management.

Topics: Adult; Aged; Calcium; Female; Gastrins; Humans; Hyperparathyroidism; Hyperplasia; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Zollinger-Ellison Syndrome

Primary gastrin cell hyperfunction of the gastric antrum as a clinical syndrome consists of basal hypergastrinemia, an exaggerated gastrin response to feeding, the absence of any ectopic source of gastrin secretion, and peptic ulcer disease. The number of G-cells were quantitated in the gastric antrum of five patients with clinically diagnosed primary G-cell hyperfunction, and the results were compared to controls with a variety of gastric diseases. Patients with the clinical diagnosis of primary G-cell hyperfunction had a significantly increased number of antral G-cells (p less than 0.05). The clinical syndrome of primary G-cell hyperplasia appears to be associated with hyperplasia of G-cells rather than with the hypersecretion of gastrin by a normal number of G-cells.

Topics: Adult; Chromaffin System; Diagnosis, Differential; Enterochromaffin Cells; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Peptic Ulcer; Pyloric Antrum; Stomach Diseases; Syndrome; Zollinger-Ellison Syndrome

A method for measurement of gastrin in human antral mucosa or in extragastric tissue has been developed and validated. Tissue gastrin was extracted by boiling followed by homogenization at neutral pH. Extractable gastrin immunoreactivity was measured by radioimmunoassay using an antiserum with equal affinity towards G-17 I, G-17 II, G-34 I and G-34 II molecular forms. Almost all extractable gastrin immunoreactivity was recovered after a single extraction and no significant interference by other peptides and/or substances present in tissue was found. The mean gastrin concentration in antral mucosa of healthy subjects was similar to that observed in duodenal ulcer patients, while patients with type A chronic atrophic gastritis or with antral gastrin cell hyperplasia had mean values significantly higher. Gastrin concentration in all specimens from gastrinoma or its metastases was above the upper limit of the range of control tissue. Measurement of tissue gastrin seems to be a valuable tool in the diagnosis of antral gastrin cell hyperplasia and Zollinger-Ellison syndrome.

Topics: Adolescent; Adult; Aged; Cholecystitis; Chronic Disease; Duodenal Ulcer; Female; Gastric Mucosa; Gastrins; Gastritis; Humans; Hyperplasia; Male; Middle Aged; Pancreatic Neoplasms; Pyloric Antrum; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrectomy; Gastrins; Humans; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Recurrence; Zollinger-Ellison Syndrome

The serum values of PG I and gastrin have been established in a normal population and in several clinical diseases. The PG I is raised in duodenal, gastric, and pyloric ulcer even though the gastrin is normal. Both PG I and gastrin values are raised in renal insufficiency and the Zollinger-Ellison syndrome. The PG I is lowered in atrophic gastritis and alcoholic cirrhosis, and is at the limit of detection in Biermer anemia and total gastrectomy. Insulin and sham-feeding are stimulants for PG I release by patients with duodenal ulcer, but no correlation is observed between PG I output and PAO in the studied group. The results show that PG I is able to distinguish between associated hypergastrinemia and hypoacidity (Biermer anemia type) or a hyperacidity (Zollinger-Ellison syndrome type), and that PG I is a good indicator for gastric hypoacidity. Overlapping between normal and ulcer subjects is comparable to those obtained in acid output determinations.

Topics: Adolescent; Adult; Aged; Anemia, Pernicious; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Gastritis, Atrophic; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Pepsinogens; Reference Values; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Celiac Artery; Female; Gastrins; Humans; Male; Middle Aged; Portal Vein; Radiography; Zollinger-Ellison Syndrome

A commercially available radioimmunoassay designed for quantitating human gastrin was evaluated for use in quantitating dog gastrin. Because of the similarities in molecular structures of the two, the assay appears to be useful for dogs. Serum gastrin concentration in 12 fasting dogs averaged 64.8 pg/ml. After dogs were fed, the concentration increased to 117.8 pg/ml within 30 minutes and returned to base line by 90 minutes. A standard feeding procedure may be useful in evaluating dogs with gastrinoma.

Topics: Animals; Dog Diseases; Dogs; Eating; Fasting; Female; Gastrins; Male; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adult; Carcinoid Tumor; Female; Gastrins; Humans; Male; Middle Aged; Serotonin; Thymus Neoplasms; Zollinger-Ellison Syndrome

Two peptides which copurified from a human gastrinoma were found to correspond to the amino acid sequence deduced for the amino terminal portion of human and porcine progastrin. The sequence of peptide A is Ser-Trp-Lys-Pro-Arg-Ser-Gln-Gln-Pro-Asp-Ala-Pro-Leu-Gly-Thr-Gly-Ala-Asn- Arg-Asp-Leu-Glu-Leu which is identical to an amino terminal portion of human progastrin. The sequence of peptide. B is identical to that of peptide A except it is missing the first five amino acids. If peptide A corresponds to the amino terminus of progastrin, the signal peptidase cleaves at an Ala-Ser bond.

Topics: Amino Acid Sequence; Animals; Gastrins; Genes; Humans; Peptide Fragments; Protein Precursors; Species Specificity; Swine; Zollinger-Ellison Syndrome

Gastroduodenal rugal enlargement is associated with gastric acid hypersecretion. This study investigates the effects on the upper gastrointestinal (GI) examination of gastric acid suppression by cimetidine. Radiographs were evaluated for gastric and small-bowel fold size, small-bowel dilatation, and the presence of fluid in the stomach and small bowel. Six patients with basal gastric-acid hypersecretion (three with ordinary duodenal ulcer disease and three with Zollinger-Ellison syndrome) were studied. Results revealed that hypersecretors with ordinary duodenal ulcer disease could not be distinguished from those with Zollinger-Ellison syndrome by means of the upper GI study. The effects on the GI examination of the acid suppression by cimetidine were apparent in four of the six patients. Relations between observed radiographic effects and basal acid output and cimetidine dose were suggested only among the duodenal ulcer disease patients.

Topics: Adolescent; Adult; Cimetidine; Digestive System; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Radiography; Zollinger-Ellison Syndrome

Operative experience with 45 gastrinoma patients has led to the identification of an anatomic area where occult tumors can be discovered and where excision of these tumors had led to apparent cure. Of 36 patients with histologically confirmed gastrinomas, 27 patients (75 percent) had obvious and 9 patients (25 percent) had occult tumors. All nine occult lesions were found within an anatomic triangle defined by the junction of the cystic and common bile ducts superiorly, the junction of the second and third portions of the duodenum inferiorly, and the junction of the neck and body of the pancreas medially. Although occult tumors from three patients (in the lymph nodes in two patients and in the duodenum in one patient) were removed primarily for histologic diagnosis, postoperative serum gastrin levels have remained within the normal range (follow-up of 86 to 99 months). Two patients had excision of the tumor with intent to cure. One patient with a solitary duodenal tumor was apparently cured but committed suicide 3 months postoperatively. The other patient had both obvious primary and occult metastatic tumors within the triangle and was eugastrinemic 9 months after excision. In all patients in whom tumor was found, it was locally excised, and no patient was subjected to radical pancreatic resection. There were no postoperative complications related to tumor removal. An aggressive approach towards curative tumor excision is now advocated for all gastrinoma patients who are suitable operative risks and have no evidence preoperatively of liver metastases or the multiple endocrine neoplasm-type I syndrome.

Topics: Biopsy; Duodenal Neoplasms; Follow-Up Studies; Gastrins; Humans; Liver Neoplasms; Lymphatic Metastasis; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

In a patient with Zollinger-Ellison syndrome, control of the peptic ulcer diathesis was attempted by excision of a small duodenal gastrinoma and removal of three lymph nodes containing metastases. The patient has been asymptomatic for 2.5 years with basal achlorhydria, a normal serum gastrin level and a negative gastrin response to secretin. Our experience with this patient emphasizes the fact that the presence of metastatic disease does not preclude the possibility of long-term control of hypergastrinemia by resection of the tumor. Attempts to cure the Zollinger-Ellison syndrome by tumor resection alone, however, should only be made in patients whose hypersecretion is adequately controlled by antisecretory drugs.

Topics: Antacids; Female; Gastrins; Humans; Middle Aged; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Epinephrine; Gastric Acid; Gastrins; Humans; Pyloric Antrum; Zollinger-Ellison Syndrome

A secretin provocative test was performed in 16 patients with chronic duodenal ulcer and in five patients with the Zollinger-Ellison syndrome. In four chronic duodenal ulcer patients a second secretin test was done during acute iv cimetidine administration. There were only slight variations of gastrin compared with the first test. A third test was done on the same four chronic duodenal ulcer patients after 1 month's po cimetidine treatment (1 g/day); gastrin at 0 time was significantly higher than in the previous two tests (p less than 0.01). Integrated gastrin response after secretin was significantly lower in the third test than in the first (p less than 0.05). In two Zollinger-Ellison syndrome patients treated with 1.0 and 1.4 g/day cimetidine for 3 months, gastrin at 0 time was not markedly increased, whereas compared with the first test gastrin levels were higher at each time after secretin. These data suggest that previous cimetidine treatment does not alter, and may even increase, the diagnostic sensitivity of the secretin test.

Topics: Adolescent; Adult; Chronic Disease; Cimetidine; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

In 28 patients with the Zollinger-Ellison syndrome (ZES), 26 studied before and two after tumor excision, and in 26 age-matched control patients with duodenal ulcer (DU), plasma pancreatic polypeptide and serum gastrin concentrations were studied before, during, and after infusion of pure secretin (3 CU/kg/hr). In 21 ZES patients, gastric acid output was simultaneously studied. Fasting pancreatic polypeptide concentrations were over 300 pmol/liter in five of 26 gastrinomas. In DU, secretin caused a nonsignificant increase in plasma pancreatic polypeptide concentration and markedly decreased gastric acid output. In ZES, however, it resulted in a marked increase of both plasma pancreatic polypeptide concentration and gastric acid output. Basal and post secretin pancreatic polypeptide concentrations showed no correlation with gastric acid output, serum gastrin levels, or the age of the subjects, in DU patients as well as in ZES. These concentrations were not different in ZES patients who had a vagotomy compared to nonvagotomized ZES patients. Furthermore, the pancreatic polypeptide response to intravenous secretin was abolished by gastrinoma excision.

Topics: Adult; Duodenal Ulcer; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pancreatic Polypeptide; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Cimetidine; Diagnosis, Differential; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Humans; Male; Multiple Endocrine Neoplasia; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Protein Precursors; Radioimmunoassay; Reagent Kits, Diagnostic; Zollinger-Ellison Syndrome

Exploratory laparotomy and a search for gastrinomas was performed in 52 patients with the Zollinger-Ellison syndrome (ZES). Gastrinoma tissue was resected in 11 patients (21%), 6 (12%) of whom appear to have been cured. After surgery, serum gastrin levels in these six patients have remained normal from 10 months to 10 years. In the 46 other patients, tumor was unresectable because of metastases or multiple primary tumors (21 patients; 40%) or inability to find the tumor at laparotomy (21 patients; 40%). Multiple pancreatic islet cell adenomata were found in six of seven patients with multiple endocrine neoplasia (MEN), indicating that patients with this condition usually have diffuse involvement of the pancreas. The results of CT scans correlated with findings at laparotomy in 13 of 16 patients. The smallest tumor detected by CT scans was 1 cm in diameter. CT technology is more accurate in finding gastrinomas now than in the past and has a useful role in preoperative evaluation. The possibility of resection should be seriously considered in every patient with Zollinger-Ellison syndrome. Abdominal CT scans, transhepatic portal venous sampling, and laparotomy should be used to find the tumor and to determine whether it is resectable. Using presently available methods, it should be possible to cure about 25% of patients with gastrinomas who do not have MEN and over 70% of those without MEN who appear to have a solitary tumor. Total pancreatectomy may be necessary to cure some patients with MEN, but that operation is rarely justified. The morbidity and mortality of surgical attempts at curing this disease have become minimal; we have had no deaths or serious complications following such operations in over 10 yrs. Total gastrectomy and indefinite use of H2-receptor blocking agents are the therapeutic options for patients with unresectable gastrinomas. Because H2-receptor blocking agents fail to control acid secretion in many patients after several yrs of therapy, total gastrectomy is indicated in a large proportion of patients whose tumors cannot be resected. Total gastrectomy in patients with ZES is also safe using current techniques; our last death following this operation for ZES occurred 15 yrs ago.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Female; Gastrectomy; Gastrins; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Postoperative Complications; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Topics: Adult; Gastrins; Humans; Hyperparathyroidism, Secondary; Male; Multiple Endocrine Neoplasia; Parathyroid Hormone; Parathyroid Neoplasms; Pituitary Neoplasms; Prolactin; Zollinger-Ellison Syndrome

In the last 10 years, the basis for the diagnosis and treatment of gastric hypersecretion in Zollinger-Ellison syndrome has changed dramatically. The diagnostic criteria have changed because gastrin hypersecretion by a non-beta islet tumor is now known to be responsible for gastric hypersecretion, and gastrin radioimmunoassays are now widely available. The treatment of the gastric hypersecretion in Zollinger-Ellison syndrome has changed since development of histamine H2-receptor antagonists and the demonstration that gastric acid secretion can be controlled medically in most patients, obviating routine total gastrectomy. In this paper, we review currently available and newer antisecretory drugs, the results of long-term medical treatment, potential problem areas, and our current approach to controlling gastric hypersecretion in patients with Zollinger-Ellison syndrome.

Topics: Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Parasympatholytics; Prostaglandins E, Synthetic; Zollinger-Ellison Syndrome

This paper reports a personal experience in the management of 45 patients with recurrent ulcer after gastric surgery. Inadequate acid reduction was the major cause of ulcer recurrence and treatment was by further acid reduction. Revisional surgery was performed in 23 patients (including a patient with a gastro-jejuno-colic fistula) with one mortality. Preliminary results of therapy with histamine H2-receptor antagonists have been encouraging and there appears to be a reduced need for re-operation in these patients in recent years. Less common causes of ulcer recurrence include retained suture material (2 cases) and the Zollinger-Ellison syndrome (2 cases). The incidence of post-surgical ulcer recurrence may be reduced by: improved surgical techniques, particularly in the performance of vagotomy, and avoidance of operations without acid reducing procedures e.g., gastro-jejunostomy without vagotomy; wider use of emergency ulcer curative surgery for perforated peptic ulcer. Experience at two local centres has been that this is a safe procedure in selected patients, there being no mortality in 58 cases. Routine screening of peptic ulcer patients for the Zollinger-Ellison Syndrome by measuring the serum gastrin level facilitates early diagnosis of the condition, thus forestalling gastric surgery and the inevitable recurrent ulceration.

Topics: Combined Modality Therapy; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Pentagastrin; Peptic Ulcer; Peptic Ulcer Perforation; Recurrence; Vagotomy; Zollinger-Ellison Syndrome

Clinical and endoscopic findings were compared with 24-hr pH profiles in 8 patients with Zollinger-Ellison syndrome (ZES), who were being treated, during consecutive periods, with doses of cimetidine or ranitidine. There was a positive correlation between the effect on gastric pH and the outcome of treatment, with ranitidine proving to be more effective. The reduction of gastric acidity was correlated with ranitidine plasma levels. In the medical management of ZES patients, the 24-hr pH profile appears to be a measurement which is of value in the choice of appropriate drug regimes and which promises to increase our understanding of treatment failure.

Topics: Adult; Aged; Cimetidine; Drug Evaluation; Female; Furans; Gastric Acid; Gastric Acidity Determination; Gastrins; Guanidines; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Monitoring, Physiologic; Ranitidine; Time Factors; Zollinger-Ellison Syndrome

There are few detailed studies of patients with pathological hypergastrinaemia of antral origin. We have identified four patients with severe acid hypersecretion associated with peptic ulcer disease and in whom no evidence for gastrinoma or isolated retained antrum could be found. Three of these patients also had hypergastrinaemia. In two patients, one with gastric ulcers and one with duodenal ulcer disease, the hypergastrinaemia appeared to be due to antral gastrin cell hyperfunction and there was also evidence for mild antral gastrin cell hyperplasia. In the other hypergastrinaemic patient, a primary intestinal gastrin cell hyperfunction syndrome was suspected, but a hidden gastrinoma could not be excluded. The remaining patient had nearly fatal hypersecretory ulcer disease and cimetidine failed to control the hypersecretory state. In this patient the hypersecretion responded to a more potent H2 antagonist with resolution of a metabolic encephalopathy. No general pathophysiological mechanism could be identified in these patients or in larger groups of patients with gastric or duodenal ulcer disease.

Topics: Adult; Aged; Duodenal Ulcer; Duodenum; Gastric Acid; Gastrins; Humans; Male; Peptic Ulcer; Pyloric Antrum; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Cat Diseases; Cats; Duodenal Ulcer; Female; Gastrins; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Sulfated gastrins were quantitated in sera from 15 patients with the Zollinger--Ellison syndrome (ZES) by specific radioimmunoassays. The total concentration of gastrin varied from 174 to 285 000 pmol/l. Sulfated gastrins constituted 44.8 +/- 5.5% (mean +/- S.E.M.) of the gastrins in ZES sera compared with 37.7 +/- 1.9% in sera from 100 control subjects (P greater than 0.1). There was no correlation between gastrin concentration and sulfation (r = 0.40). Gel and ion-exchange chromatography showed that up to 90% of the gastrins could be in the sulfated form. The highest degree of sulfation was found in sera where the small gastrin components dominated. Thus, the percentage of small gastrins (G-17 and G-14) correlated with the degree of sulfation (N = 15, r = 0.75, P less than 0.01). We suggest therefore that proteolytic processing of the gastrin precursor and sulfation of tyrosyl are associated.

Topics: Female; Gastrins; Humans; Male; Middle Aged; Molecular Weight; Neoplasm Metastasis; Radioimmunoassay; Sulfuric Acid Esters; Sulfuric Acids; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrins; Humans; Liver Neoplasms; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Female; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Postgastrectomy Syndromes; Zollinger-Ellison Syndrome

The prevalence of gastrinomas and the Zollinger-Ellison syndrome is unknown. In order to examine a high risk group of patients, basal and secretin-provoked plasma gastrin levels were determined in 50 consecutive patients, predominantly from the west of Scotland. All had endoscopically proven recurrent peptic ulceration following duodenal ulcer surgery. This resulted in three cases strongly suspected of having a gastrinoma. Further investigations including exploratory laparotomy were unable to demonstrate a gastrinoma in two, but the evidence suggested an occult tumour in one. In this remaining unoperated patient, the serum gastrin returned to normal. The reference range for both basal and secretin stimulated gastrin response and percentage change has been determined in normal control subjects (n = 10) and in primary ulcer patients (n = 20). It is concluded that in this study, gastrinomas had a less than 2 per cent prevalence in patients presenting with recurrent peptic ulceration. As the diagnosis of a gastrinoma changes the surgical approach, conducting screening tests still seems warranted.

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Recurrence; Scotland; Secretin; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Zollinger-Ellison Syndrome

A radioimmunochemical procedure which distinguishes sulfated from non-sulfated gastrins has been developed. Two antisera raised against synthetic non-sulfated human hexadecapeptide gastrin were used. No. 2604 binds sulfated and non-sulfated gastrins with equimolar potency, whereas No. 2605 reacts poorly with sulfated gastrin (ID50 for non-sulfated gastrin: ID50 for sulfated gastrin = 0.06). Both antisera bind gastrins of different molecular length with equimolar potency using monoiodinated human gastrin-17 as tracer. The method was validated by fractionating gastrins in serum and in tissue extracts, and by recovery experiments. We found that Component I of gastrin--like the smaller gastrin components--was present in both, sulfated and non-sulfated form. In serum from normal fasting subjects the concentration of non-sulfated gastrin was 12.5 +/- 0.8 pmol/l (mean +/- SEM) with a total range of 0-44 pmol/l and the corresponding values for sulfated gastrin were 7.5 +/- 0.5 pmol/l (range 0-20 pmol/l). Sulfated gastrin accounted for more than half of the gastrins in only 21% of normal subjects. There was a parallel rise and fall in sulfated and non-sulfated gastrins after a meal and after stimulation with adrenaline.

Topics: Animals; Eating; Epinephrine; Gastrins; Humans; Pyloric Antrum; Radioimmunoassay; Sulfuric Acids; Swine; Zollinger-Ellison Syndrome

The use of secretin in the biochemical and roentgenologic diagnoses of a duodenal gastrinoma has been described. Preoperatively, the secretin test indicated that a gastrinoma and not a retained antrum was the cause of hypergastrinemia in a patient who had previously undergone Billroth II gastrectomy. Intravenous infusion of secretin during selective angiography resulted in greatly enhanced visualization of the tumor which allowed it to be localized to the duodenal stump. Several months postoperatively, the secretin test result had become negative, which presumably suggested that the tumor had been excised completely. Our experience has revealed that intravenous secretin might improve the diagnostic usefulness of selective angiography.

Topics: Aged; Duodenal Ulcer; Gastrins; Humans; Male; Radiography; Secretin; Zollinger-Ellison Syndrome

When the Zollinger-Ellison syndrome was first identified, total gastrectomy was proposed as the most effective treatment for the secretory manifestations of the syndrome. Recently, however, great enthusiasm has developed for medical treatment by means of H2-receptor antagonists. The authors have cared for 27 patients with the Zollinger-Ellison syndrome at The University of Texas Medical Branch in the past 12 years and have been pleased with the results of total gastrectomy, which was performed in 23 of the 27 patients (one patient refused operation and three patients had lesser gastric operations). Twenty-three patients underwent total gastrectomy with Roux-en-Y esophagojejunostomy. There were no operative deaths. Primary tumors were found in 17 patients, seven of whom also had metastatic tumors. No tumors were found in nine patients. Nine patients are dead; the actuarial survival rate for all patients was 75% at 5 years and 52% at 10 years. Eleven of the 27 patients had the multiple endocrine neoplasia I syndrome. Of the 18 survivors, only three have normal serum gastrin levels, and all three had extrapancreatic gastrinomas, one in peripancreatic lymph nodes, one in the liver, and one in a cystic tumor attached to the stomach. Nutritional results were good to excellent, with a mean postoperative weight loss of 14.7% (mean follow-up period was 45 months). The authors conclude that treatment of the hypersecretory problems of the Zollinger-Ellison syndrome by total gastrectomy is safe and dependable. Results compare well with those of long-term medical management, whose success is dependent upon serial favorable responses to a lifetime of repeated challenges.

Topics: Adolescent; Adult; Aged; Cimetidine; Female; Gastrectomy; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Postoperative Period; Zollinger-Ellison Syndrome

In an attempt to determine the best provocative test for the diagnosis of gastrinoma, ten normal subjects, 13 patients with known gastrinoma, and one patient with presumed gastrinoma were administered four regimens: (1) rapid calcium infusion (2 mg Ca++/kg/min), (2) secretin (2 clinical units (CU)/kg/bolus), (3) long calcium infusion (12 mg Ca++/kg/3 h) and (4) a combination test consisting of a rapid calcium infusion followed immediately by secretin. Blood was drawn for serum gastrin levels before and following infusion of the test agents. The administration of rapid calcium followed by secretin provoked the greatest increases in serum gastrin above basal levels in both normals (29%) and patients (362%). Peak gastrin levels in patients were similar following the long calcium infusion (341%) but were less following the rapid calcium infusion alone (124%) and secretin alone (207%). There were no false-positive or false-negative tests with the calcium plus secretin when the criterion for diagnosis was either a 50% increase or a 200 pg/ml increase above the basal gastrin level. The distinct advantages (short test period, low patient morbidity, and relatively great potency) of the calcium plus secretin test make it an attractive alternative to other previously described provocative tests for the diagnosis of gastrinoma.

Topics: Adult; Aged; Calcium; Calcium Gluconate; Female; Gastrins; Gluconates; Humans; Infusions, Parenteral; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Topics: Calcitonin; Gastrins; Humans; Liver Diseases; Peptic Ulcer; Time Factors; Zollinger-Ellison Syndrome

The number of G- and D-cells per area and the ratio of G/D-cells were investigated in biopsy specimens of the pyloric antrum from normochlorhydric subjects without peptic ulcer, from patients with duodenal ulcer, gastrinoma, pernicious anaemia, and after selective proximal vagotomy. Compared with normochlorhydric subjects antral G-cell density was significantly raised in pernicious anaemia, unchanged in duodenal ulcer, and diminished in gastrinoma patients. After vagotomy G-cell density was found to be raised if compared with patients with duodenal ulcer. D-cell density was significantly increased in gastrinoma patients, unchanged in duodenal ulcer, and diminished in pernicious anaemia and after vagotomy. The G/D-cell ratio was increased in pernicious anaemia and after vagotomy, unchanged in duodenal ulcer, and decreased in gastrinoma patients. It is concluded that the antral pH governs the ratio of G- and D-cells. Therefore, the G/D cell ratio increases in states of reduced acid secretion and decreases in massive hyperchlorhydria. Hypergastrinaemia as such does not affect the G/D-cell ratio.

Topics: Adult; Anemia, Pernicious; Cell Count; Duodenal Ulcer; Female; Gastric Acid; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pyloric Antrum; Somatostatin; Vagotomy, Proximal Gastric; Zollinger-Ellison Syndrome

In approximately 20% of the cases the Zollinger-Ellison syndrome (ZES) is associated with primary hyperparathyroidism (HPT). In view of this frequent association, serum calcium and phosphorus levels should be measured in all patients with ZES. Conversely, all patients with HPT I accompanied or preceded by peptic ulcer and/or diarrhoea should have their gastric acid secretion and serum gastrin level measured. Since the association may reflect a type I multiple endocrine neoplasia (MENI), involvement of other endocrine systems, notably the pituitary gland, should be investigated in the patients and their family. A rise in basal plasma pancreatic polypeptide has been observed in about 50% of cases of familial MEN I (Wermer's syndrome) and appears to be a good index of pancreatic endocrine tumour. When ZES is associated with HPT I, the latter should be treated first for three reasons: (7) lethal acute hypercalcaemia may occur after abdominal surgery; (2) HPT I itself may increase the gastric acid secretion and hypergastrinaemia of the ZES, and (3) parathyroidectomy and medical treatment with gastric antisecretory drugs may postpone the need for total gastrectomy.

Topics: Adult; Female; Gastric Acid; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Polypeptide; Parathyroid Glands; Zollinger-Ellison Syndrome

In three families with the multiple endocrine adenomatosis type I (MEA I) trait, 51 members were investigated by measurement of circulating peptide hormones as tumor markers. Twenty-five of 51 members (49 percent) were considered to be affected by MEA I disorders. The incidence rose with age (75 percent in generation II). Both sexes were affected equally. Hyperparathyroidism was present in 20 of 25 affected members (80 percent), and pituitary tumors (prolactinomas) were found in four of 25 (16 percent). Endocrine pancreatic tumors were found in nine of 25 affected members (36 percent), but when "probable" tumors (seven) are included the frequency rises to 72 percent. Hyperparathyroidism was found in all except one member with proved lesions in other organs. Among patients with proved and possible endocrine pancreatic tumors, elevated serum levels of gastrin and pancreatic polypeptide were frequently found, 78 percent and 67 percent, respectively, and we suggest that serum gastrin and pancreatic polypeptide levels are the most useful screening markers at present for pancreatic lesions in MEA I.

Topics: Adenoma; Adolescent; Adult; Age Factors; Aged; Female; Gastrins; Humans; Hyperparathyroidism; Insulinoma; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Parathyroid Neoplasms; Pedigree; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Blood Specimen Collection; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Veins; Zollinger-Ellison Syndrome

The technique and validation of the cytochemical section bioassay for gastrin-like activity are described. This assay utilises the measurement of hormone-induced changes of carbonic anhydrase activity in guinea-pig gastric parietal cells. The clinical use of the assay as identified elevated levels of fasting gastrin-like biological activity in the plasma of patients with duodenal ulcer and has also demonstrated discrepancies between radioimmunoreactive gastrin levels, biological activity, and the clinical presentation of peptic ulcer disease.

Topics: Adult; Animals; Aprotinin; Duodenal Ulcer; Fasting; Female; Gastric Mucosa; Gastrins; Guinea Pigs; Histocytochemistry; Humans; Male; Middle Aged; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Acupuncture Therapy; Adult; Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Gastritis, Atrophic; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Peptic Ulcer; Pyloric Antrum; Stomach Diseases; Zollinger-Ellison Syndrome

This study was undertaken to determine whether or not the serum gastrin response to secretin in patients with Zollinger-Ellison syndrome is influenced by changes in serum calcium. After infusion of 50 mg/kg disodium ethylenediaminetetraacetate over 90 min in 7 patients with Zollinger-Ellison syndrome, increases in serum gastrin following administration of 1 CU/kg (Cu-clinical unit) secretin GIH (118 +/- 46 pg/ml) were lower than the response before the infusion (755 +/- 90 pg/ml; p less than 0.01). Before infusion of disodium ethylenediaminetetraacetate all 7 patients with Zollinger-Ellison syndrome had gastrin increases after secretin administration above 100 pg/ml, while after the infusion 4 of 7 patients had secretin-stimulated increases in serum gastrin below 100 pg/ml. Subsequent normalization of serum calcium by infusion of 3 mg/kg calcium over 15 min resulted in gastrin responses to secretin of greater than 100 pg/ml. Infusion of 10 mg/kg calcium over 120 min in 4 Zollinger-Ellison syndrome patients induced significant increases in secretin-stimulated serum gastrin from 660 +/- 180 to 1339 +/- 286 pg/ml (p = 0.005). This dose of calcium did not increase the gastrin response to secretin in 5 normogastrinemic and 2 hypergastrinemic control subjects. It was concluded that serum gastrin response to secretin in patient with Zollinger-Ellison syndrome is influenced by serum calcium concentrations.

Topics: Adult; Calcium; Edetic Acid; Female; Gastrins; Humans; Infusions, Parenteral; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

After an exposition of the modern trends on the definition, ethiopathogenesis, symptomatology and therapy of the Zollinger-Ellison Syndrome, the authors presents a case of Z.-E. Syndrome, which occurred to their observation.

Topics: Cimetidine; Gastric Juice; Gastric Mucosa; Gastrins; Gastroscopy; Humans; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Cimetidine; Gastrins; Humans; Zollinger-Ellison Syndrome

Patients with the Zollinger-Ellison syndrome have been managed by total gastrectomy and more recently, by the use of H2-receptor antagonists. An alternative approach has been to identify those who might be cured by excision of a pancreatic islet-cell tumor without removal of the stomach. The course of such a patient is reported. A 40-yr-old man with massive gastric hypersecretion, acid-peptic disease, diarrhea, and elevated serum gastrin was treated by excising a pancreatic gastrinoma. Serum gastrin and gastric secretion became and have remained normal for 7 yr. Symptoms ceased and provocative tests with secretin and calcium have remained normal. Three additional patients with Zollinger-Ellison syndrome in whom pancreatic islet-cell tumor resection alone has resulted in long-term cures have been identified. All were middle-aged men with severe diarrhea. These successes, the availability of techniques that permit early identification and localization of gastrinomas, and the advent of H2-receptor antagonists that can control gastric hypersecretion without gastrectomy must be considered in managing patients with gastrinomas.

Topics: Adult; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Male; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Serum gastrin responses to bombesin and to food were studied in patients with hypergastrinemia. Nine unoperated patients with hypergastrinemia of antral origin (seven achlorhydria by two idiopathic G-cell hyperfunction) had significantly higher serum gastrin responses to bombesin (P less than 0.001) and to food (P less than 0.001) than eight unoperated patients with Zollinger-Ellison syndrome. Three gastrectomized Zollinger-Ellison patients showed large serum gastrin responses to bombesin, and two of them had large postprandial increases in serum gastrin. Serum gastrin in a single patient with retained excluded antrum in the duodenal stump after partial gastrectomy with Billroth II anastomosis responded to bombesin but not to food. In nonoperated patients with hypergastrinemia of antral origin, the serum gastrin responses to bombesin and to food were significantly correlated (r = 0.786; P less than 0.02) while in unoperated Zollinger-Ellison patients no such correlation was found (r = 0.095; P greater than 0.10). It is concluded that determination of the serum gastrin response to bombesin does not provide more information than measurement of postprandial serum gastrin concentrations in the differential diagnosis of patients with basal hypergastrinemia.

Topics: Adult; Aged; Bombesin; Eating; Female; Gastrectomy; Gastrins; Humans; Male; Middle Aged; Peptides; Pyloric Antrum; Zollinger-Ellison Syndrome

In a small percentage of patients with ulcer disease, a gastrinoma may be ultimately discovered. In most institutions, a fasting serum gastrin determination and gastric analysis are as first-line tests to identify this subgroup of patients with ulcer disease. The blood test is relatively inexpensive and well accepted by patients. Gastric analysis is uncomfortable and required a well-equipped facility staffed by skilled personnel. A prospective study designed to assess the diagnostic usefulness of these tests and, particularly, whether combining both tests adds to the individual value of each, revealed that gastric analysis does not improve the diagnostic ability of the fasting serum gastrin test. Therefore, gastric analysis probably is not indicated for determining whether a patient with active ulcer disease has a gastrinoma. The fasting serum gastrin test will suffice, and abnormal values on this test should be verified by the use of other tests such as responses to gastrin provocative tests.

Topics: Adolescent; Adult; Aged; Child; Diagnosis, Differential; Duodenal Ulcer; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Prospective Studies; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Cimetidine; Diagnosis, Differential; Duodenal Ulcer; Gastric Acidity Determination; Gastrins; Humans; Prospective Studies; Zollinger-Ellison Syndrome

Topics: Cimetidine; Gastrins; Humans; Zollinger-Ellison Syndrome

A gastrinoma was found in 12 of 23 patients with Zollinger-Ellison syndrome. Those with gastrinoma were not different from those without as regarded fasting gastrin level, increased gastrin secretion after secretin and calcium, acid secretion, or survival time. Five of the 23 patients have died, four immediately postoperatively, the fifth of the metastasizing tumour. Treatment with the H2-receptor antagonist cimetidine avoided emergency operation and thus decreased operative mortality, giving time for localization by ultrasound, computed tomography and selective arteriography. The rate of false-negative results was high. Transhepatic selective catheterization of the pancreatic veins with gastrin determination gives localization of the tumour and identification of the secreted hormone. In three patients tumour resection was possible under cover of H2-receptor antagonist administration which normalized gastrin and acid secretion. There is a change in the treatment of the Zollinger-Ellison syndrome, away from total gastrectomy to conservative treatment with H2-receptor antagonists and an attempt of curative treatment by removal of the tumour.

Topics: Adult; Aged; Calcium; Cimetidine; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Secretin; Survival; Zollinger-Ellison Syndrome

In 10 out of 27 patients with a Zollinger-Ellison syndrome a gastrin-producing tumor was removed, in 5 localized with phlebography. In the remaining 12 patients the diagnosis of a gastrinoma was based on clinical data only. The 10 patients with surgically proven gastrinoma did not differ in their fasting blood-glucose levels, rise of gastrin serum levels after administration of secretin and calcium, in acid production patterns nor in survival time from those 12 patients in whom no gastric-producing tumor had been found. 5 of the 27 patients died, 4 just after surgery. One patient died from advanced malignant disease. In three of our patients localizing diagnostic procedures and consecutive tumor-removal were feasible with the protection of H2-receptor antagonists. The trend in the treatment of ZES goes away from elective total gastrectomy towards conservative treatment with H2-receptor antagonists in view of the low morbidity and the attempt of curative treatment by tumor-removal.

Topics: Adult; Aged; Cimetidine; Female; Gastrectomy; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adult; Diagnosis, Differential; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Portal Vein; Pyloric Antrum; Pylorus; Secretin; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Diagnosis, Differential; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Stomach Diseases; Zollinger-Ellison Syndrome

Responses of serum gastrin to both intravenous infusion of secretin (GIH secretin 3 CU/kg/hr) and intravenous bolus injection (GIH secretin 1 CU/kg) were studied in 2 Zollinger-Ellison syndrome (ZE) patients and 27 duodenal ulcer (DU) patients. In all of the DU patients, the stage of the ulcer was determined endoscopically, prior to testing, as either active or healed. We found that the responses of serum gastrin to secretin were closely related to the stage of the duodenal ulcer; serum gastrin increased in the active stage and decreased in the healed stage. In patients with active duodenal ulcer, a false positive (ZE-like) response to exogenous secretin was observed. Comparing the results of intravenous infusion and bolus administration of secretin in terms of maximal percent change of serum gastrin, there was no significant difference between the two methods, confirming the works reported by others.

Topics: Adult; Diagnosis, Differential; Duodenal Ulcer; False Positive Reactions; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

Long-term follow-up of children with the Zollinger-Ellison syndrome (gastrinomas) suggests that surgical management is still advantageous. Twenty-eight children with the Zollinger-Ellison syndrome have been followed up to 21 years after their initial surgical procedure. Six of seven children with less than total gastrectomy, all of whom underwent operation before the introduction of histamine H2-receptor antagonists, are known dead from complications of continued gastric hypersecretion and tumor growth. Sixteen children had a total gastrectomy, with no operative deaths, and only one died of progressive tumor growth, even though 14 had evidence of metastatic islet-cell carcinoma. Follow-up serum gastrin measurements have been obtained for 13 patients with total gastrectomy, and 5 patients now have a normal serum gastrin levels. Malignant gastrinomas in children have been slow growing, indolent, and compatible with long life. The biologic behavior of malignant gastrinomas appears to be more favorable in the young patient. Total gastrectomy can be done safely in children with the Zollinger-Ellison syndrome and effectively controls gastric hypersecretion when all gastrin-producing tumor cannot be excised. Surgical exploration and an attempt at "curative" tumor excision, even when tumor is extrapancreatic and in lymph nodes, appear worthwhile in selected patients.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Cimetidine; Female; Follow-Up Studies; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Peptic Ulcer; Zollinger-Ellison Syndrome

Despite the increasing awareness of gastrinoma and its lethal peptic ulcer sequelae, the diagnosis is often initially missed or made as a terminal event. The authors screened all patients with peptic ulcer symptoms serious enough to warrant hospital admission or those associated with diarrhea, nephrolithiasis, hypercalcemia, or pituitary abnormality. In a one-year period (1979-1980) nine (of 14 suspected) new gastrinoma patients were identified using a sensitive and specific gastrin radioimmunoassay in combination with provocative tests including IV secretin, calcium, and food. Conventional upper GI series, CAT scan, arteriography, and endoscopy provided no additional information other than to confirm the presence of ulcer disease. Basal plasma gastrin levels were more than 200 pmol L-1 in only three of the nine (normal fasting plasma gastrin levels are less than 25 pmol L-1). Three patients presented with acute ulcer perforation, and the diagnosis of gastrinoma was suspected because of multiple ulcers and pancreatic masses. In three other patients, previous duodenal ulcer surgery had failed. One patient with dyspepsia, high basal plasma gastrin, negative secretin and calcium infusion studies, and a positive meal test was diagnosed as having G-cell hyperplasia; this was confirmed by biopsy and antral gastrin extraction. Antrectomy alone resulted in cure. In all patients tested, a positive calcium infusion or secretin bolus (greater than 100% rise over basal) strongly suggested the diagnosis of gastrinoma, which was confirmed at surgery. In the acute perforations, initial management with omental patch and cimetidine therapy allowed survival of two patients, while emergency total gastrectomy in the third resulted in death due to esophagojejunal leak. Elective patients were treated with cimetidine initially for at least two weeks before total gastrectomy. In this group there were no operative mortalities, and postoperative morbidity was minimal. This series illustrates three important points: (1) careful screening of an ulcer population using gastrin radioimmunoassay and provocative tests has enabled a high yield of gastrinomas while conventional investigations are of minimal values; (2) a high index of suspicion in appropriate cases is necessary; and (3) total gastrectomy performed under elective circumstances is safe and allows the patients to resume a normal and healthy life without the sequelae of aggressive peptic ulceration or daily drug administration

Topics: Adult; Calcium Gluconate; Diagnosis, Differential; Female; Gastrectomy; Gastrins; Humans; Male; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

Topics: Chromatography, Ion Exchange; Gastrins; Humans; Liver Neoplasms; Prognosis; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Calcium; Cimetidine; Diagnosis, Differential; Female; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

The topical nature of the treatment of Zollinger-Ellison syndrome arises from the alternatives to total gastrectomy, namely medical management with cimetidine, and tumorectomy. The various stages in the history of the syndrome are described with reference to a personal series of 16 cases, and various observations are made with regard to the clinical aspects of its diagnosis, treatment, and emergency surgical management. A detailed account is given of several illustrative cases. Detailed assessment of the various factors on which the current indications for surgery are based suggests that a certain degree of eclecticism should be adopted, though the results offered by total gastrectomy must be regarded as sound in the long term.

Topics: Adult; Cimetidine; Female; Gastrectomy; Gastrins; Guanidines; Humans; Middle Aged; Zollinger-Ellison Syndrome

Topics: Adult; Female; Fetal Blood; Gastrins; Humans; Hypertrophy; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Neoplastic; Pyloric Stenosis; Zollinger-Ellison Syndrome

Topics: Adult; Cimetidine; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Adult; Endoscopy; Female; Gastrins; Humans; Male; Middle Aged; Time Factors; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Child; Diagnosis, Differential; Female; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

The secretin injection test has been proved to be useful in the diagnosis of gastrinoma in vivo. Fresh gastrinoma cells were cultured for a short time in vitro and then stimulated with secretin. A rise in the gastrin concentration in the culture medium was observed within 10 min after the addition of secretin. This fact may be evidence that gastrinoma cells have receptors which bind with secretin resulting in the release of gastrin.

Topics: Cells, Cultured; Female; Gastrins; Humans; In Vitro Techniques; Injections, Intravenous; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Emergency Medical Services; Gastrectomy; Gastrins; Humans; Laparotomy; Radioimmunoassay; Zollinger-Ellison Syndrome

Glucagon provocation test was performed in the patients with hypergastrinemia and hyperchlorhydria to investigate its diagnostic value. A paradoxical response of plasma gastrin level in the patients with the Zollinger-Ellison syndrome and a marked decrease of plasma gastrin level in the patients with gastric ulcer, duodenal ulcer, excluded gastric antrum, multiple endocrine adenomatosis, pernicious anemia and chronic renal failure were demonstrated by glucagon infusion. Glucagon provocation test, therefore, was considered to be of great value in the diagnosis of the Zollinger-Ellison syndrome, particularly, in the case of an excluded gastric antrum in which secretin provocation test caused the false positive result because of a marked increase of pancreatic secretion. Glucagon provocation test in combination with secretin provocation test, therefore, is at present the most preferable diagnostic procedure for detecting the Zollinger-Ellison syndrome.U

Topics: Adult; Diagnosis, Differential; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Glucagon; Humans; Kidney Failure, Chronic; Middle Aged; Multiple Endocrine Neoplasia; Pyloric Antrum; Secretin; Stomach Ulcer; Zollinger-Ellison Syndrome

It is now evident that hypersecretion of gastric hydrochloric acid is an important pathogenetic element among a variety of heterogeneous factors responsible for the production of common duodenal ulcer. Hypersecretion of gastric acid due to usually strikingly increased circulating levels of gastrin released from gastrinoma tissue is characteristics of patients with to Zollinger-Ellison Syndrome. In contrast, fasting serum gastrin levels are normal in patients with common duodenal ulcer. The polypeptide hormone, gastrin does, however, appear to play subtle and multiple roles in enhancement of gastric acid secretion in duodenal ulcer. Recent evidence suggests that abnormalities in gastrin release and action may be influenced by participation of somatostatin. The hypothesis is proposed for consideration and for further investigation that the multiple subtle abnormalities in gastrin release and parietal cell sensitivity to gastrin may be due to disturbances in the actions or concentrations of locally acting polypeptides, substances which are capable of suppressing gastrin release and its effects (somatostatin), or alternatively, are capable of stimulating release of gastrin into the circulation (bombesin).

Topics: Bombesin; Duodenal Ulcer; Gastric Acid; Gastrins; Humans; Somatostatin; Zollinger-Ellison Syndrome

Topics: Furans; Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Ranitidine; Zollinger-Ellison Syndrome

The development of peptic ulcer surgery is traced from 1881 and Billroth until the present. Discussion of the physiologic basis for gastric resection, the several types of vagotomy, and antrectomy is presented as conceived by the surgeons who originated these operations. Treatment of the complications of peptic ulcer surgery is discussed as well as the current diagnostic and therapeutic approach to the Zollinger-Ellison syndrome.

Topics: Animals; Dogs; Drainage; Duodenal Diseases; Gastrins; History, 19th Century; History, 20th Century; Humans; Intestinal Perforation; Jejunum; Peptic Ulcer; Pyloric Antrum; Stomach; Vagotomy; Zollinger-Ellison Syndrome

Gastroesophageal reflux has rarely been reported in the Zollinger-Ellison syndrome, presumably due to elevation in the lower esophageal sphincter pressure. We have evaluated 15 patients with the Zollinger-Ellison syndrome for evidence of esophageal disease. Five presented initially with esophageal disease: one, reflux symptoms; two, severe esophagitis; and two, strictures. Six of 15 had heartburn and nine of 15, objective evidence for reflux disease. Mean lower esophageal sphincter pressure was higher in the Zollinger-Ellison syndrome than in controls but was unrelated to serum gastrin levels. Zollinger-Ellison syndrome patients without heartburn had a higher mean sphincter pressure than did patients with heartburn (who had a mean sphincter pressure similar to that of controls but greater than that in patients with idiopathic gastroesophageal reflux). Four patients had biopsy evidence of esophagitis, one in association with Barrett's epithelium. Gastroesophageal reflux and its complications appear to be common in the Zollinger-Ellison syndrome.

Topics: Adult; Esophagogastric Junction; Esophagoscopy; Female; Gastrins; Gastroesophageal Reflux; Heartburn; Humans; Male; Manometry; Middle Aged; Prospective Studies; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Duodenoscopy; Female; Gastrectomy; Gastric Acid; Gastrins; Gastroscopy; Humans; Male; Middle Aged; Vagotomy; Zollinger-Ellison Syndrome

Topics: Calcium; Follow-Up Studies; Gastrins; Humans; Organotechnetium Compounds; Prognosis; Radioimmunoassay; Secretin; Sugar Acids; Zollinger-Ellison Syndrome

Topics: Adult; Diagnosis, Differential; Female; Gastrins; Humans; Hyperplasia; Peptic Ulcer; Pyloric Antrum; Zollinger-Ellison Syndrome

Topics: Gastrins; Glucagon; Humans; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Gastrins; Hormones; Male; Rats; Stimulation, Chemical; Zollinger-Ellison Syndrome

The purpose of the investigation was to detect ulcer patients having nontumorous hypergastrinemic hyperchlorhydria and to diagnostically differentiate this pseudo-Zollinger-Ellison syndrome from neurogenic duodenal ulcer disease and pancreatic gastrinomas. Nine patients having clinical, radiologic and humoral findings simulating the Zollinger-Ellison syndrome or severe duodenal ulcer disease were studied by physiologic provocative testing. The patients, not having pancreaticoduodenal gastrinomas, had an antral mucosal source of their moderate hypergastrinemia even after vagotomy with drainage, which was eliminated in eight patients treated by surgical antrectomy, resulting in normal serum gastrin concentrations. The pseudo-Zollinger-Ellison syndrome is, thus, characterized physiologically by an exaggerated gastrin response to meals, no response to secretin stimulation and pathologically by hyperfunctioning hyperplastic G cells of the antrum. The clinical, physiologic, pathologic and surgical features were integrated for accurate diagnosis and treatment.

Topics: Adult; Aged; Calcium; Diagnosis, Differential; Duodenal Ulcer; Eating; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Secretin; Stomach Diseases; Zollinger-Ellison Syndrome

We analyzed 186 secretin provocation tests performed in our laboratory over a 5 year period. Positive tests, i.e., an increase in serum gastrin of more than 100 pg/ml, were found in 3 of 136 normogastrinemic and in 30 of 50 hypergastrinemic subjects. In all 16 patients with positive tests who were operated upon the diagnosis of gastrinoma was confirmed. In the 17 nonoperated patients the diagnosis of gastrinoma was supported by the demonstration of gastric acid hypersecretion. Two normogastrinemic patients with questionable gastrinoma had increases in serum gastrin of 72 and 73 pg/ml, respectively. Five patients with combined hypergastrinemia and basal hyperchlorhydria had negative secretin provocation tests: three had hypergastrinemia of antral origin, one had a gastrin-producing ovarian cystadenocarcinoma, and one had a pancreatic gastrinoma with liver metastases. We conclude that the secretin provocation test is helpful in the diagnosis of gastrinoma.

Topics: False Negative Reactions; Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

Topics: Cystadenocarcinoma; Female; Gastrins; Humans; Middle Aged; Ovarian Neoplasms; Zollinger-Ellison Syndrome

Two personal cases of Zollinger-Ellison syndrome (ZES) are described. Total gastrectomy (TG) was performed in the first case as an emergency measure, following acute peritonitis caused by a recurrence of ulcer, with perforation 27 days after the first gastric resection. The patients is in good health, though with persistently high blood gastrin levels. The second case was marked by a long history of recurrent ulcer, with two earlier gastric resections. Here, success was obtained by simply enucleating a small gastrinoma from the head of the pancreas in view of the arteriographic evidence. The patient is in excellent health 2 1/2 yr after surgery with stable, normal blood gastrin. The recent literature and these cases suggest that surgery is the method of choice for ZES, its primary aim being the removal of gastrinomas, since these prove malignant in 60-100% of cases, and TG does not in any way inhibit their growth, as was once supposed. Blood gastrin values permit early diagnosis and postoperative monitoring, while arteriography and transhepatic portal catheterisation constitute a useful guide to the location of the tumour. Hyperchlorhydria can be effectively controlled with H2 receptor inhibitors, both in the preoperative diagnostic stage, and after surgery in the event of failure. TG offers the best results in over 60% of cases, when the tumours is multifocal, widely metastasised, or undiscoverable.

Topics: Adult; Angiography; Female; Gastrectomy; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer Perforation; Peritonitis; Postoperative Complications; Zollinger-Ellison Syndrome

The effect of sulfuric acid esterification of Tyr-12 in gastrin-17 on immunoreactivity was evaluated by the ability of seventeen antisera raised against non-sulfated gastrin-17 to bind sulfated gastrins in extracts of gastrinoma and antral tissue. Using non-sulfated Tyr-12 iodinated gastrin as tracer, and non-sulfated gastrin-17 as standard the antisera showed three different patterns of reactivity: Three antisera (Nos. 2602, 2605 and 4562) bound sulfated gastrins with low (4-23%) potency; four antisera (Nos. 2604, 2720, 4710 and 4713) measured sulfated gastrins with a potency similar to that of non-sulfated gastrins (81-100% crossreactivity); whereas ten antisera (Nos. 2601, 2606, 2609, 2716, 2717, 2718, 4556, 4559, 4560 and 4563) displayed enhanced reactivity with sulfated gastrins (130-373% crossreactivity). Using Gly-2 iodinated gastrin as tracer, the latter type of antisera reacted almost equally with sulfated and non-sulfated gastrins, suggesting that the apparent increase in binding of sulfated gastrins rather is due to increased displacement of Tyr-12 iodinated gastrin. The results show that derivatization of amino acid residues greatly influences antibody binding.

Topics: Animals; Antibody Specificity; Esterification; Gastric Mucosa; Gastrins; Humans; Immunochemistry; Rabbits; Radioimmunoassay; Sulfuric Acids; Tyrosine; Zollinger-Ellison Syndrome

A case of hypergastrinemia, diarrhea, and relentless hypokalemia occurring in a middleaged, mildly hypertensive female is described. The presence of a gastrinoma was suggested by the additional findings of an inordinate degree of hypokalemia for the amount of thiazide used for the treatment of her hypertension; failure of her hypokalemia to correct itself with adequate doses of oral potassium that had previously corrected this problem; and amelioration of her symptoms and hypokalemia when she was treated with short-term oral potassium chloride and longterm cimetidine.

Topics: Diarrhea; Female; Gastrins; Humans; Hypertension; Hypokalemia; Middle Aged; Zollinger-Ellison Syndrome

Topics: Adult; Cimetidine; Female; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Adult; Diagnosis, Differential; Esophageal Stenosis; Esophagitis, Peptic; Esophagoscopy; Gastrins; Humans; Male; Zollinger-Ellison Syndrome

In 67 patients with two-thirds gastrectomy and endoscopically proven stomal ulcer, serum gastrin levels were measured under basal conditions and after intravenous infusion of bombesin (15 ng/kg/min), calcium (4 mg/kg/hour) and secretion (2 units/kg). All patients underwent medical or surgical therapy. The long-term results were evaluated according to the Visick grading system (average follow-up, 3.1 years).

Topics: Antacids; Bombesin; Calcium; Cimetidine; Female; Gastrectomy; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Parasympatholytics; Recurrence; Secretin; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Preliminary data showed that bombesin stimulated serum gastrin levels in patients with the Zollinger-Ellison syndrome (ZES). In this study, the total immunoreactive gastrin and the different molecular forms of gastrin were measured in 16 patients with ZES (11 with proved pancreatic gastrinoma, 2 with proved duodenal gastrinoma and 3 with uncertain tumour localization) following bombesin infusion and following calcium infusion in 13 patients. In all patients with gastrinoma (both pancreatic and duodenal) bombesin augmented serum gastrin levels. In patients with pancreatic gastrinoma calcium infusion was a more potent stimulator of gastrin secretion than bombesin. In the 2 patients with duodenal gastrinoma bombesin was more potent than calcium in stimulating serum gastrin levels with a basal/stimulated gastrin level ratio similar to the ratio found in patients with incomplete antrectomy. These data suggest that gastrin-producing cells from duodenal gastrinomas may be more closely related to the normal antral G cells than to the gastrin-producing cells from pancreatic gastrinomas. Furthermore, the comparison between the basal/calcium and the basal/bombesin stimulated gastrin levels may help in differentiating preoperatively patients with pancreatic gastrinoma from patients with retained antral mucosa. In all the patients studied, bombesin augmented the concentration of all of the gastrin components considered. These data support the hypothesis that G 34, G 17 and the N-terminal G 17 fragment are all present in gastrinomas.

Topics: Bombesin; Calcium; Gastrectomy; Gastrins; Humans; Peptide Fragments; Peptides; Zollinger-Ellison Syndrome

Insulinoma, glucagonoma, gastrinoma (Zollinger-Ellison syndrome), vipoma, somatostatinoma and a tumor that secretes human pancreatic polypeptide are the primary endocrine-secreting tumors of the pancreas. hormones are produced by specific tumor cell types and cause a variety of dramatic clinical pictures. Diagnosis often requires hormone assays. Computerized tomography may be helpful. Definitive surgical treatment is possible, but metastases may be present.

Topics: Adenoma, Islet Cell; Apudoma; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

In order to test tthe hypothesis that chronically elevated serum gastrin levels induce hypercalcitoninaemia, we have measured serum calcitonin levels in patients with chronic hypergastrinaemia. Basal serum calcitonin concentrations were found to be elevated in 2 of 23 patients with Zollinger-Ellison syndrome, but not in 16 patients with hypergastrinaemia due to achlorhydria or a single patient with primary hypergastrinaemia of antral origin. Both Zollinger-Ellison patients with hypercalcitoninaemia (0.31 and 0.79 ng/ml) had multiple endocrine adenomatosis type 1, but no medullary carcinoma of the thyroid. The hypercalcitoninaemia in these patients does not seem to be related to multiple endocrine adenomatosis type 1, since serum calcitonin was normal in 12 normogastrinaemic patients with hyperparathyroidism from families with multiple endocrine adenomatosis type 1. We conclude that chronically elevated serum gastrin levels do not result in hypercalcitoninaemia.

Topics: Calcitonin; Chronic Disease; Gastrins; Humans; Multiple Endocrine Neoplasia; Zollinger-Ellison Syndrome

An islet cell carcinoma of the pancreas is described in a 68-year old woman which clinically produced Zollinger-Ellison syndrome and, later in its course, Cushing syndrome. The tumor was found to contain gastrin, ACTH, alpha-endorphin, somatostatin and calcitonin, by the immunoperoxidase technic. Electron microscopy revealed a single tumor cell type containing secretory granules of variable size, morphology and electron density. It appears that a single tumor cell population produced all five hormones and caused a transition in clinical symptomatology, while undergoing no change in morphology.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Aged; Calcitonin; Cushing Syndrome; Endorphins; Female; Gastrins; Hormones, Ectopic; Humans; Immunoenzyme Techniques; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Somatostatin; Zollinger-Ellison Syndrome

A family with Multiple Endocrine Adenomatosis Type 1 (MEA 1) is described. Of the 59 members, 15 were affected. Zollinger-Ellison syndrome was present in six individuals of whom the five available for study had hyperparathyroidism. The youngest of these patients with Zollinger-Ellison Syndrome was 25 years old. Hyperparathyroidism alone was present in nine individuals of whom the eldest was 30 years old. Three other members had raised serum gastrin levels but lacked symptoms suggestive of Zollinger-Ellison syndrome and in these individuals, the serum calcium levels were normal. A review of the literature confirms the finding that, in MEA 1, Zollinger-Ellison syndrome has not been shown to occur in the absence of hypercalcaemia. Screening of affected members of such families can therefore be restricted to the measurements of serum calcium levels.

Topics: Adolescent; Adult; Calcium; Child; Female; Gastrins; Humans; Hypercalcemia; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Pedigree; Zollinger-Ellison Syndrome

Topics: Adult; Calcium; Female; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Phosphorus; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Animals; Blood Group Antigens; Child; Coronary Disease; Disease Models, Animal; Disease Susceptibility; Diseases in Twins; Ethnicity; Female; Gastric Emptying; Gastrins; Genetic Markers; Humans; Kidney Calculi; Lung Diseases; Male; Mice; Mice, Inbred NZB; Middle Aged; Models, Genetic; Multiple Endocrine Neoplasia; Pepsinogens; Peptic Ulcer; Urticaria Pigmentosa; Zollinger-Ellison Syndrome

The main clinical signs of three dogs with Zollinger-Ellison syndrome were vomiting, diarrhoea, poor appetite and weight loss. The diagnosis was confirmed by histological examination and by gastrin immunocytochemistry. Gastrin was extracted from pancreatic tumours of two dogs. Gastrin-component III predominated in one dog while gastrin-component II and gastrin-component III were demonstrated in almost equal amounts in the other dog. In one dog serum gastrin concentration was high. Postmortem examination revealed pancreatic tumours in all three dogs and metastases in the regional lymph nodes and liver in two. The pancreatic tumours contained three patterns of growth: solid, trabecular and acinar. Electron microscopy of liver metastases showed cells with secretory granules. In all three dogs there was an erosive oesophagitis and thick gastric mucosa caused mainly by glandular proliferation. Two dogs had erosions and ulcers in the duodenum, one also in the first part of the jejunum. Villous atrophy and cellular infiltration of the duodenal mucosa were found in all dogs.

Topics: Adenoma, Islet Cell; Animals; Dog Diseases; Dogs; Esophagus; Female; Gastrins; Intestines; Male; Pancreatic Neoplasms; Stomach; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Insulin Secretion; Pancreatic Hormones; Secretin; Zollinger-Ellison Syndrome

It has now been well established that the ulcerogenic syndrome associated with non-beta islet cell tumors of the pancreas is due to excess gastrin release and consequent marked gastric acid hypersecretion. The clinical manifestations may be similar to, but are often more severe and recurrent than, common peptic ulcer. The diagnosis of gastrinoma in patients with this clinical syndrome can be established principally by demonstration of fasting hypergastrinemia, and by application of provocative tests with measurement of serum gastrin in response to intravenous calcium infusion, intravenous secretin injection and feeding of a standard meal. Gastrinomas are usually located within the pancreas, are often multifocal and metastatic, but may be primary in non-pancreatic sites. There is substantial heterogeneity in the molecular forms of circulating and gastrinoma gastrin. Although hypergastrinemia is characteristic of gastrinoma, serum gastrin levels may be increased in disorders other than gastrinoma. Techniques are available to document the presence of gastrin in islet cell tumors and, thereby, to establish these as gastrinomas.

Topics: Adenoma, Islet Cell; Calcium; Diagnosis, Differential; Duodenum; Fasting; Gastrins; Humans; Injections, Intravenous; Pancreas; Secretin; Stomach; Zollinger-Ellison Syndrome

The immunoreactive form of gastrin released by the islets and some of the characteristics of this release have been studied. This gastrin released by the islets in the present experiments corresponds to what has been named "Big Big" gastrin in serum of patients with the Zollinger-Ellison syndrome, in normal human serum and in extracts of proximal jejunum. Most of the "Big Big" gastrin released from the islets corresponds to spontaneous release.

Topics: Animals; Gastric Mucosa; Gastrins; Humans; In Vitro Techniques; Islets of Langerhans; Jejunum; Male; Rats; Zollinger-Ellison Syndrome

Topics: Deoxyglucose; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Humans; Hydrogen-Ion Concentration; Insulin; Pentagastrin; Recurrence; Specimen Handling; Vagotomy; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastrins; Humans; Secretin; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Calcium; Gastrins; Humans; Molecular Weight; Pentagastrin; Peptic Ulcer; Pyloric Antrum; Zollinger-Ellison Syndrome

Techniques for evaluating ectopic gastrin production associated with the Zollinger-Ellison syndrome are described. The site of gastrin production in this example was a mucinous cystadenoma of the ovary confirmed by immunoperoxidase localization of gastrin within the ovarian tumor cells and by radioimmunoassay of the tumor's gastrin content. These methods, localizing the source of ectopic gastrin, permitted conservative management of the ulcer diathesis with surgical resection of the mucinous cystadenoma. After oophorectomy the patient's serum gastrin level returned to normal, and the ulcer diathesis ceased.

Topics: Cystadenoma; Female; Gastrins; Hormones, Ectopic; Humans; Middle Aged; Ovarian Neoplasms; Ovary; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Animals; Dogs; Duodenum; Gastrins; Molecular Weight; Pancreas; Physiology; Secretin; Zollinger-Ellison Syndrome

A 58-year-old man developed diarrhoea and duodenal ulcer related to a malignant pancreatic gastrinoma. Initial evaluations of basal acid output and serum gastrin level were not significant. Two months later they were typical of Zollinger-Ellison syndrome. The tumor was detected by endoscopic retrograde pancreatography.

Topics: Endoscopy; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Pancreatic Ducts; Zollinger-Ellison Syndrome

Topics: Adult; Gastrins; Humans; Male; Peptic Ulcer; Pyloric Antrum; Zollinger-Ellison Syndrome

We determined the relative concentrations of gastrin molecular species in serum samples from 21 patients with Zollinger-Ellison syndrome with localized gastrinoma (n = 11) or gastrinoma with hepatic metastases (n = 10). Gastrin molecular species were separated by gel-filtration chromatography and quantitated by radioimmunoassay with a gastrin antiserum produced in our laboratory. The percentage gastrin-17 of the total gastrin in the two groups differed significantly (nonparametric Wilcoxon rank test; p less than 0.01). Patients with the Zollinger-Ellison syndrome with apparently localized gastrinoma had a lower percentage of G- 17 (7.6%, SEM 1.6%) than did patients with gastrinoma with hepatic metastases (31.1%, SEM 6.1%). This procedure may be useful in the early classification of tumors in patients with Zollinger-Ellison syndrome.

Topics: Gastrins; Humans; Liver Neoplasms; Neoplasm Metastasis; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Urticaria Pigmentosa; Vagotomy; Zollinger-Ellison Syndrome

Gastrin 1--17 protected against physiological proteolysis does not change gastric acid secretion and serum gastrin level even if present in the duodenal and gastric lumen in excessive amounts. Consequently gastric juice gastrin has no local effect on the parietal cell. There is no measurable resorption of gastrin from the gastric or duodenal lumen. Gastrin 1--17 does not liberate endogenous gastrin from the antral and duodenal mucosa. Thus, an indirect systemic influence of gastric juice gastrin on the function of the parietal cell can be excluded. Gastric juice gastrin seems to be a waste-product of a bidirectional G-cell secretion. Gel filtration and starch block electrophoresis revealed considerable amounts of immunoreactive material in the duodenal perfusate resembling gastrin 1--34. Thus, the duodenal G-cells seem to liberate gastrin into the duodenal lumen.

Topics: Duodenal Ulcer; Duodenum; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Zollinger-Ellison Syndrome

Radio-immunoassay of serum gastrin may now be carried out in all laboratories of radio-immunology. Comparison of two commercial kits A: Schwartz-Mann and B: CEA-SORIN according to criteria of specificity, sensitivity and reproducibility within and between systems, shows that they both permit the detection of pathological hypergastrinemias (Zollinger Ellison and atropic gastritis). Both kits have an identical intra-system coefficient of variation (10 p. cent and 7 p. cent for A, 5 p. cent and 8 p. cent for B) on the other hand, the inter-system coefficient of variation is better for kit B (22,4 p. cent and 37 p. cent for kit A, and 11,5 p. cent and 14,2 p. cent for kit B). The normal values for each kit are quite different: 97 + 64 pg.ml-1 for A and 51 . 23 pg.ml-1 for B preventing one from comparing estimations carried out with two different kits.

Topics: Adenoma; Evaluation Studies as Topic; Gastrins; Radioimmunoassay; Reference Values; Zollinger-Ellison Syndrome

The Zollinger-Ellison syndrome (ZES) is characterized by gastrin-producing tumors, gastric acid hypersecretion, peptic ulcers, and diarrhea. ZES may be associated with nonpancreatic endocrine tumors as part of the multiple endocrine adenomatosis-type 1 syndrome. The diagnosis of ZES can be confirmed in patients with a suggestive clinical picture and excessive gastric acid secretion by the finding of a markedly elevated fasting serum gastrin level or characteristic gastrin response to provocative testing. Standard treatment of ZES has traditionally been surgical. With the introduction of H2-histamine receptor antagonists, however, many patients can now be managed successfully with cimetidine alone, or cimetidine plus vagotomy, when no resectable gastrinoma is present.

Topics: Adolescent; Adult; Aged; Child; Female; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

A 61-year-old man with a 20-year history of recurrent gastric peptic ulcerations had an adenocarcinoma of the esophagus resected. The carcinoma was associated with columnar cell-lined (Barrett's) esophagus with carcinoma in situ. The patient had hypergastrinemia (gastrin level, 1,000 pg/dl), and at autopsy two months after the operation, a 3-mm pancreatic adenoma was discovered. In addition to the rarity of this clinical constellation, the case is of interest in suggesting that hypergastrinemia does not protect against peptic esophagitis and its sequelae.

Topics: Adenocarcinoma; Esophageal Diseases; Esophageal Neoplasms; Esophagitis, Peptic; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: C-Peptide; Chemical Phenomena; Chemistry; Gastrins; Hormones; Humans; Peptides; Proinsulin; Radioimmunoassay; Zollinger-Ellison Syndrome

Prior to total gastrectomy, serum levels of gastrin and human chorionic gonadotropin (HCG) and its alpha- and beta-subunits (alpha-HCG and beta-HCG) were determined by radioimmunoassays in 40 patients with the Zollinger-Ellison syndrome. Basal serum gastrin levels greater than 1,500 pg/mL were found only in patients with metastases to lymph nodes or liver, while levels greater than 8,000 indicated massive liver replacement by tumor. Gastrin levels less than 1,500 pg/mL had no correlation with malignant behavior. Neither the calcium-infusion nor secretin-injection test was useful in identifying tumors as benign or malignant. Basal serum levels of alpha-HCG were elevated (> 7 ng/mL) in four of 20 patients with metastatic gastrinoma and were normal in all 16 patients with benign disease. There was a significant correlation between basal gastrin and alpha-HCG levels in patients with malignant gastrinoma but not for those with benign tumors. The results suggest that serum gastrin and alpha-HCG levels can be useful in assessing the biologic behavior of gastrinomas and in planning appropriate surgical and nonsurgical treatment.

Topics: Adult; Chorionic Gonadotropin; Female; Gastrectomy; Gastrins; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Zollinger-Ellison Syndrome

Topics: Animals; Calcium Gluconate; Evaluation Studies as Topic; False Negative Reactions; Gastrins; Hormones; Humans; Infusions, Parenteral; Injections, Intravenous; Secretin; Swine; Zollinger-Ellison Syndrome

It is unknown whether the gastrin response to secretin (secretin test) can distinguish hypergastrinemia due to vagotomy from hypergastrinemia due to Zollinger-Ellison syndrome (ZES). Therefore, we measured serum gastrin concentrations basally and in response to intravenous secretin in 13 vagotomized duodenal ulcer patients without preoperative evidence evidence of ZES and in 5 vagotomized patients with ZES. Following secretin, serum gastrin concentrations increased 40 pg/ml or less [mean (+/- SE) rise 23 +/- 3 pg/ml] in the vagotomized patients without ZES. On the other hand, in the patients with ZES serum gastrin increments after secretin ranged from 105 to 1224 pg/ml. Thus, a large (> 100 pg/ml) rise in serum gastrin concentrations following secretin in a vagotomized patient should suggest Zollinger-Ellison syndrome and not be attributed to vagotomy per se.

Topics: Diagnosis, Differential; Duodenal Ulcer; Gastrins; Hormones; Humans; Injections, Intravenous; Secretin; Vagotomy; Zollinger-Ellison Syndrome

The previously assigned structure of human big gastrin is revised as a result of sequencing and immunological studies on synthetic peptides. A nonadecapeptide has been synthesized and found to have full immunochemical potency compared with natural human G34 in a radioimmunoassay which is specific for the N-terminal sequence. Syntheses of the peptides were achieved using the stepwise procedure with benzyloxycarbonyl-amino acids and fragment couplings mediated mainly by the dicyclohexylcarbodiimide procedure in the presence of either N-hydroxysuccinimide or 1-hydroxybenzotriazole. Purification of the peptide fragments was by Sephadex LH-20 chromatography and removal of protecting groups was effected using 90% trifluoroacetic acid in the presence of scavengers. Purification of the nonadecapeptide was achieved by high performance liquid chromatography.

Topics: Amino Acid Sequence; Amino Acids; Chemical Phenomena; Chemistry; Gastrins; Humans; Protein Precursors; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Animals; Brain Chemistry; Cholecystokinin; Dogs; Gastric Acid; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Swine; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adult; Gastric Juice; Gastric Mucosa; Gastrins; Gastroscopy; Humans; Male; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Female; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adult; Catheterization; Duodenum; Female; Gastrins; Humans; Liver; Pancreatectomy; Portal Vein; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Hypoglycemia; Pancreatic Neoplasms; Skin Manifestations; Zollinger-Ellison Syndrome

A father and son each presented with severe watery diarrhea. The son was found to have a pancreatic islet-cell tumor associated with the pancreatic cholera syndrome, as well as a parathyroid adenoma. The father was found to have multiple islet-cell adenomas and the Zollinger-Ellison syndrome. Pancreatic tumor tissue from each patient contained detectable gastrin and vasoactive intestinal peptide; however, a much higher gastrin concentration was found in the tumor tissue from the father and a much higher vasoactive intestinal peptide content in the tumor tissue from the son. Thus, watery diarrhea may be mediated by different hormones in families having multiple endocrine neoplasia; the precise cause of the diarrheal syndrome should be defined to ensure the proper therapy.

Topics: Adenoma; Adenoma, Islet Cell; Adult; Diarrhea; Endocrine System Diseases; Gastrins; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Parathyroid Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Conventional or electron microscopy can contribute significantly to the diagnosis of pancreatic endocrine tumours. These techniques, however, are of limited value for the classification of the tumours, which should take both clinical and morphological findings into account. In this paper a classification based on both the clinical features and on the content of peptide hormone-producing cells in the tumours is presented.

Topics: Adenoma, Islet Cell; Cushing Syndrome; Gastrins; Glucagon; Humans; Malignant Carcinoid Syndrome; Pancreatic Neoplasms; Somatostatin; Zollinger-Ellison Syndrome

Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Intestinal Neoplasms; Motilin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

The role of human pancreatic-polypeptide in endocrine tumours of the pancreas is reviewed. Pancreatic-polypeptide may be involved in 3 different ways: 1. In cases with pure PP producing tumours. 2. In mixed endocrine tumours containing PP cells. 3. In cases with PP cell hyperplasia in normal pancreatic tissue associated with endocrine pancreatic tumours as VIP-omas, insulinomas, and glucagonomas. PP does not seem to serve as a general marker for endocrine tumours of the pancreas, but PP determinations are useful in patients wbith watery diarrhoea syndromes, because such syndromes may be associated with tumours that contain PP cells. Large molecular forms of PP occur in plasma from patients with endocrine tumours and high PP concentrations, but may also be found in other groups of patients. It is suggested that an atropin-suppression test could be of diagnostic value in revealing patients with increased serum concentrations of PP from other causes than vagal stimulation of normal PP cells.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastrins; Glucagon; Humans; Hyperplasia; Molecular Weight; Pancreas; Pancreatic Neoplasms; Pancreatic Polypeptide; Syndrome; Zollinger-Ellison Syndrome

Gastro-entero-pancreatic (GEP) and bronchial endocrine tumours have been studied by immunohistochemistry using specific antisera against a variety of hormonal and neuronal peptides. In gastrinomas numerous tumour cells were found to contain GH-like immunoreactivity. These cells were identical with those storing gastrin. Gastrinomas as a rule were extremely heterogeneous containing a variety of minority cell populations, including CCK immunoreactive cells and neurotensin immunoreactive cells. Glucagonoma cells were found to store GIP-like material in addition to glucagon. In some insulinomas calcitonin-like material was encountered in the insulin producing tumour cells. In both glucagonomas and insulinomas other pancreatic endocrine cell types constituted minority cell populations. One intestinal somatostatinoma contained gastrin cells as a minority cell population. Bronchial endocrine tumours contained scattered cells displaying ACTH-like or enkephalin-like immunoreactivity. Two such tumours in addition contained cells displaying neurophysin immunoreactivity.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Bronchial Neoplasms; Cholecystokinin; Enkephalins; Fluorescent Antibody Technique; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Neurophysins; Pancreatic Neoplasms; Serotonin; Somatostatin; Stomach Neoplasms; Zollinger-Ellison Syndrome

Recent clinical experiences with 34 Z-E patients indicates that the clinical features and course of the syndrome is less dramatic than described originally. Eighty-five per cent of the patients presented stories of abdominal complaints lasting more than five years and resembling the complaints presented by duodenal ulcer patients (DU). Ulcers were present in 91 per cent of the patients. Fifty-one per cent had either ectopic or multiple ulcers. One third had a single duodenal ulcer resembling an ordinary ulcer. No patients died from complications to the ulcer diathesis. Marked hypersecretion of acid and gastrin was present in the ZE group (BAO:33.7 +/- 7.4; PAO:62.8 +/- 6.1 meq H+/h; gastrin: 5094 pmol/l), but because of great individual variation in the ZE, some overlapping with the acid and gastrin measurements of the DU was seen. The diagnostic value of provocative tests using secretin, calcium, glucagon and food stimulations demonstrated a considerable overlapping between the two groups, indicating that these tests are of little clinical value. Tumours were found in half the patients, revealing malignancy in ten. The ZE can be diagnosed in most cases by combining symptomatology, with measurements of acid and gastrin.

Topics: Adult; Aged; Calcium; Female; Food; Gastric Juice; Gastrins; Glucagon; Humans; Male; Middle Aged; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

A 58-year-old patient with hypergastrinemia (basal and after stimulation by means of protein food, calcium, glucagon, and secretin), acid hypersecretion, recurrent anastomotic ulcer, gastrocolonic fistula, steatorrhea, and malabsortion (hypocalcemia, hypocholesterolemia and a rather elevated 5-HIAA) is reported. The definite preoperative diagnosis of Zollinger-Ellison syndrome was established after the intravenous secretin test (75 U) which produced a significant stimulation peak 5 minutes after being injected. The possible existence of a multiple endocrine adenomatosis syndrome type I was discarded. During the operation no pancreatic or extrapancreatic macroscopic tumor was found. A total gastrectomy, transverse colectomy, splenectomy, and subtotal pancreatic resection were performed; Rosanow's techniques was used to re-established the gastrointestinal continuity. The morphological study of the excised pancreatic tissue showed a diffuse hyperplasia of the Langerhans islet cells; indirect immunofluorescence in the presence of antigastrin antibodies was faintly positive and difficult to evaluate. However, gastrin levels clearly decrease after the operation may be because the inhibitory effect of total gastrectomy or because of the partial pancreatectomy. Furthermore, the inhibitory effect of tyrocalcitonine onthe pre- and postoperative gastrin levels measured by radioimmunoassay could be verified. For the moment the importance of this test in the diagnosis of Zollinger-Ellison syndrome, and especially in the diagnosis of ZES-type II, is not known.

Topics: Calcium; Gastrectomy; Gastrins; Glucagon; Humans; Hypertrophy; Injections, Intravenous; Islets of Langerhans; Male; Middle Aged; Pancreatectomy; Secretin; Stimulation, Chemical; Zollinger-Ellison Syndrome

Parietal cell autoantibody (PCA), basal gastrin, and calcium-stimulated gastrin were measured in twenty patients with achlorhydria, in eight patients with the Zollinger-Ellison syndrome, and in fifty control subjects. In twelve patients with achlorhydria with a spared antrum, PCA was positive and basal gastrin was elevated. In contrast, eight achlorhydric patients with antral gastritis had negative PCA and significantly lower basal gastrin levels. Patients with the Zollinger-Ellison syndrome did not demonstrate positive PCA despite elevated levels of basal gastrin, nor was PCA present in normal controls. This study suggests that certain achlorhydric states are caused by an autoimmune response, particularly if antral function is spared.

Topics: Achlorhydria; Anemia, Pernicious; Autoantibodies; Calcium; Gastrins; Gastritis; Humans; Stomach; Zollinger-Ellison Syndrome

Topics: Adolescent; Animals; Gastrectomy; Gastric Juice; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Peptic Ulcer; Pyloric Antrum; Vagotomy; Zollinger-Ellison Syndrome

Seventeen of 37 healthy volunteers participating in studies of acid secretion and 1 patient with Zollinger-Ellison syndrome became rapidly and profoundly hypochlorhydric. A mild illness with epigastric pain occurred in 9 subjects, usually several days before detection of hypochlorhydria. Gastric mucosal biopsy specimens taken from subjects during hypochlorhydria revealed severe fundal and antral gastritis; however, even when acid secretion was severely depressed, parietal cells were abundant and appeared normal histologically. During hypochlorhydria, gastric permeability to hydrogen, sodium, and lithium was normal in 4 subjects. Serum gastrin concentrations were usually normal, whereas serum pepsinogen concentrations were invariably elevated. Serum parietal cell antibodies were not present. Acid secretion returned to near baseline levels in 14 of 17 subjects after a mean of 126 days (range 53--235); severity of gastritis diminished concurrently in 7 of 10 subjects on whom biopsies were serially performed. An infectious etiology is suspected, although serologic studies and bacterial and conventional viral cultures of stool and gastric juice have not identified a candidate agent.

Topics: Achlorhydria; Adult; Aged; Dietary Proteins; Disease Outbreaks; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Middle Aged; Pepsinogens; Pyloric Antrum; Zollinger-Ellison Syndrome

A 35-year-old man with the Zollinger-Ellison syndrome who is alive and well 20 years following diagnosis at age 15, is represented. At the initial operation for a bleeding duodenal ulcer a ZE tumor of the pancreas also was excised. After two additional ineffective ulcer operations, total gastrectomy was performed. At that time, retroperitoneal and peripancreatic metastases were noted, and several were removed. Three years later at laparotomy, extensive hepatic metastases were biopsied as well. Spontaneous remission occurred and when re-explored at age 34, after 14 years, no metastases were identifiable in any area. The serum gastrin level has remained elevated, casting doubt upon its value as a criterion for evaluation of tumor recurrence or activity. Other additional interesting aspects are discussed. The importance of elimination of the acid-secreting cells by total gastrectomy is emphasized. The patient remains well.

Topics: Abdominal Neoplasms; Adolescent; Adult; Gastrectomy; Gastrins; Humans; Male; Neoplasm Metastasis; Remission, Spontaneous; Time Factors; Zollinger-Ellison Syndrome

A rare case of the Zollinger-Ellison syndrome associated with hyperparathyroidism and ectopic gastric tissue in the lower esophageal mucosa is reported. Preoperatively the patient, a 53-year-old woman, had hyperchlorhydria and her fasting serum gastrin concentration was mildly elevated. There was a considerable increase in the gastric acid output and concentration of serum calcium after secretin infusion. At operation the patient had a gastric ulcer 10 cm in diameter, an islet cell tumour of the pancreas 14 cm in diameter, and ectopic gastric mucosa in the distal third of the esophagus. A gastrectomy was perfomed, the pancreatic tumour excised and part of the distal esophagus removed through a left thoracotomy. Four months after the operation the gastrin concentration had returned to low normal, but the serum calcium values remained high. One month later two parathyroid adenomas were removed which effectively cured the hypercalcemia.

Topics: Adenoma; Calcium; Choristoma; Esophageal Neoplasms; Esophagus; Female; Gastric Juice; Gastric Mucosa; Gastrins; Hormones, Ectopic; Humans; Hyperparathyroidism; Middle Aged; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Parathyroid Neoplasms; Stomach; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

Gastrinomas were localized by concurrent blood sampling in the hepatic vein and portal vein tributaries in 10 of 12 Zollinger-Ellison patients. In one patient, the portal vein could not be catheterized; in the other, a gastrin gradient could not be picked up in either of two examinations. Six of the patients were subsequently operated upon: 5 had pancreatoduodenal resection and 1 had laparotomy at which metastases were found. Four of the resections were probably curative as the patients have done well without treatment since with concentrations of gastrin in serum near zero. The observation period ranges from 17 to 20 mo. It is concluded that transhepatic catheterization of the hepatic vein and portal vein tributaries with blood sampling for gastrin determination permit the verification of the Zollinger-Ellison diagnosis and the localization of the gastrinomas. The latter may lead to the selection of a curative operative treatment in some of the patients.

Topics: Blood Specimen Collection; Catheterization; Follow-Up Studies; Gastrins; Hepatic Veins; Humans; Portal Vein; Radiography; Zollinger-Ellison Syndrome

We evaluated the effect of vagotomy on gastric acid secretion and the clinical course in 3 patients with Zollinger-Ellison syndrome. Basal acid hypersecretion was reduced by 49, 86, and 96%, and peak acid output in response to pentagastrin was reduced by 36, 39, and 71% in the 3 patients. In one patient, 300 mg cimetidine reduced basal acid secretion from 65 to 20 meq/hr before vagotomy; whereas after vagotomy basal acid secretion was reduced from 36 to 0.6 meq/hr by the same dose of cimetidine. One patient has required no antisecretory therapy for 14 yr, whereas 2 patients have also been treated with cimetidine with excellent results. We conclude that vagotomy facilitates control of acid secretion in Zollinger-Ellison syndrome, and we recommend vagotomy and cimetidine rather than total gastrectomy or cimetidine alone for the management of these patients. This combined surgical and medical approach should also allow discovery and removal of isolated tumors in about 10% of patients.

Topics: Adult; Cimetidine; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Vagotomy; Zollinger-Ellison Syndrome

Two patients with gastrinomas were treated with cimetidine and an anticholinergic drug for greater than 20 months after exploratory laparotomy disclosed no solitary resectable tumor. Both have done well, and thus this therapy is recommended as a safe and effective alternative to total gastrectomy in reliable patients. Additional therapeutic methods are needed to control tumor growth.

Topics: Administration, Oral; Adult; Antacids; Cimetidine; Drug Evaluation; Female; Gastric Juice; Gastrins; Guanidines; Humans; Male; Propantheline; Secretory Rate; Time Factors; Zollinger-Ellison Syndrome

Relationships between hormonal secretions from the GI tract and gastric functional and/or pathological abnormalities could be studied according to 2 main lines : 1) gastric secretory changes could be the main symptom of hormonal secretory tumors, i.e. acid hypersecretion in the Zollinger Ellison syndrome, acid hyposecretion in pancreatic cholera and in somatostatinoma. In these cases, hormonal hypersecretion is directly responsible for the functional disturbances and the related symptoms; 2) gastric pathological conditions are sometimes accompanied by changes in hormonal secretion, but the level of interdependence is variable : high blood gastrin is directly depending upon the atrophic gastritis in pernicious anemia; this mechanism was also suggested in case of gastric carcinoma. Concerning ulcer disease, numerous problems are unsolved in respect to blood gastrin (basal and stimulated) abnormalities, as well as somatostatin and GIP secretions.

Topics: Aged; Anemia, Pernicious; Cholera; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Pancreatic Diseases; Pancreatic Neoplasms; Somatostatin; Stomach Diseases; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

We have determined the serum gastrin response to a standard test meal in 13 unoperated patients with combined fasting hypergastrinaemia (more than 150 ng/l) and basal hypersecretion of gastric acid (BAO more than 10 mmol/h). In 10 of 11 patients with proved of presumptive Zollinger-Ellison syndrome the peak postprandial rise in serum gastrin concentration was less than 50 per cent of basal value. The integrated gastrin response to feeding ranged from 71-9 to 211-8 mug/lX 150 min. In 2 patients with proved hypergastrinaemia of antral origin, however, serum gastrin rose to 223 per cent and 255 per cent respectively of basal value after ingestion of the meal. The integrated postprandial serum gastrin responses in these patients were 66-8 and 22-0 mug/lX 150 min. Two patiets with Zollinger-Ellison syndrome and total gastrectomy showed peak serum gastrin levels after feeding of 174 and 255 per cent of basal concentration. The integrated postprandial gastrin secretions were 365 and 366 mug/l X 150 min respectively. It is concluded that the serum gastrin response to feeding, when expressed as percentage change, may be helpful in the differential diagnosis of unoperated patients with fasting hypergastrinaemia and basal gastric acid hypersecretion.

Topics: Eating; Gastrectomy; Gastric Juice; Gastrins; Humans; Postoperative Period; Time Factors; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrins; Humans; Neoplasm Invasiveness; Pancreatectomy; Zollinger-Ellison Syndrome

Topics: Animals; Anura; Bombesin; Dogs; Duodenal Ulcer; Gastrins; Gastritis; Gastrointestinal Diseases; Humans; Peptic Ulcer; Peptides; Stomach Ulcer; Zollinger-Ellison Syndrome

Thirteen patients with Zollinger-Ellison syndrome (ZES) were treated with cimetidine. This population could be divided into chronic forms, mostly presenting as a common duodenal ulcer, and acute forms resulting in critical problems requiring intensive medical care. Among the 7 patients with chronic ZES, cimetidine treatment was unsuccessful in 2; satisfactory clinical control was obtained in 3 others, but gastrinoma excision was the final treatment; cimetidine treatment has been prolonged for more than 15 months in the last 2 patients. If, in this condition, acute pharmacologic secretory inhibition were constantly obtained, therapeutic efficiency criteria are not sensitive enough to establish certainty in the patient's long-term follow-up. Total gastrectomy is still a valuable alternative if excision of the gastrinoma is not possible. Of the 6 patients with acute ZES, 4 were treated by pirenzepin (0.5 mg/kg intramuscularly 3 times a day) adjunctive to cimetidine infusion (2.4 mg/day), which resulted in increased antisecretory activity. However, total gastrectomy was the final outcome in every patient, with 1 immediate postoperative death. In conclusion, cimetidine in ZES treatment, although capable of inducing ulcer healing, diarrhea disappearance, and dramatic secretory inhibition, is still challenged by surgery, which allows either complete cure of the gastrinoma or definitive suppression of the secretory virulence.

Topics: Acute Disease; Benzodiazepines; Chronic Disease; Cimetidine; Duodenal Neoplasms; Gastrectomy; Gastrins; Guanidines; Humans; Peptic Ulcer; Piperazines; Zollinger-Ellison Syndrome

Several gastrointestinal peptides with proven or suggested endocrine or paracrine functions influence gastric acid secretion, gastrointestinal motility, and mucosal blood flow. Increased or decreased release of such factors could participate in the pathogenesis of duodenal ulcer disease by inducing increased gastric acid concentration in the duodenal bulb. To date, increased stimulation of parietal cells by gastrin has been demonstrated only in patients with gastrinoma, G-cell hyperplasia, gastric outlet obstruction, hyperparathyroidism, excluded antrum, and short bowel syndrome, but not in the usual duodenal ulcer disease. Also, a defective inhibition of parietal cell function by endocrine or paracrine factors, such as gastric inhibitory polypeptide, secretin, somatostatin and vasoactive intestinal polypeptide, seems not to exist in patients with duodenal ulcer disease. However, as long as the physiology of gastrointestinal peptides in gastric secretion and motility is not understood, a possible role of these factors in the pathogenesis of simple duodenal ulcer disease cannot be excluded.

Topics: Duodenal Neoplasms; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Prognosis; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adult; Esophagogastric Junction; Female; Gastrectomy; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Pressure; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Diagnosis, Differential; Diarrhea; Female; Gastric Juice; Gastrins; Humans; Intestinal Mucosa; Intestine, Small; Metaplasia; Microvilli; Radiography; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Calcium; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Zollinger-Ellison Syndrome

Within a ten-year scan (1967-1976) 207 insulinomas, 50 gastrinomas, 8 Verner-Morrison tumors, 5 glucagonomas and 12 endocrine pancreatic tumours with associated MEA syndrome (multiple endocrine adenomatosis) were treated surgically at various university hospitals (information obtained by questionnaire). Half of the insulinomas were treated by enucleation, one third by resection of the tail of the pancreas. Total gastrectomy was the procedure of choice in 80% of patients with gastrinoma, but sometimes pancreatic resection to remove the tumour was added. An new therapeutic concept of using histamine-H2 receptor antagonists for treating patients with Zollinger-Ellison syndrome is discussed. In the eight patients with a Verner-Morrison syndrome removal of the tumour or distal pancreatic resection was the procedure of choice.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastrectomy; Gastrins; Glucagon; Histamine H2 Antagonists; Humans; Neoplasm Metastasis; Pancreatectomy; Pancreatic Neoplasms; Statistics as Topic; Syndrome; Zollinger-Ellison Syndrome

The gastric acid, pepsin, and secretory volume output in response to a mixed meal were measured in six patients with Zollinger-Ellison syndrome caused by a gastrin-producing tumour proved subsequently at surgery. The patients were all normocalcaemic, and none had previous abdominal surgery. In four of the six patients, ingestion of the meal markedly inhibited the gastric secretory output, which decreased to below fasting levels, returning later to basal values. In two other patients, whose fasting acid output was considerably lower, the secretory output increased after the meal, but some inhibiton of gastric secretion was also apparent for variable intervals of time. The serum gastrin concentration in all patients remained essentially unchanged or increased after the meal. Two patients were restudied after successful removal of the duodenal gastrin-producing tumour, and in each the normal gastric secretory and gastrin-releasing responses were completely restored. Our studies suggest that, in patients with the Zollinger-Ellison syndrome caused by a gastrinoma, physiological regulatory mechanisms triggered by food reduce the continuous stimulation of gastric secretion caused by their tumoural hypergastrinaemia.

Topics: Adolescent; Adult; Betazole; Female; Food; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pepsin A; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Acetylcholine; Cimetidine; Gastric Juice; Gastrins; Guanidines; Histamine; Histamine H2 Antagonists; Humans; Peptic Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Mean fasting levels of pancreatic polypeptide (PP) in 24 patients with Zollinger-Ellison syndrome (ZES) and in 12 patients with hyperparathyroidism originating from families with multiple endocrine adenomatosis type I (MEAI-HPT) were significantly higher than in 72 normal controls. The overlap between the 3 groups, however, was large. In patients with ZES, increased PP levels were not related to the presence of MEAI or metastases; nor was there a correlation between serum PP and gastrin concentrations. The post-prandial PP release in 10 ZES patients and in 10 patients with MEAI-HPT was lower than in 9 normal controls. The physiological significance of the present findings is unclear.

Topics: Adolescent; Adult; Aged; Fasting; Female; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Neoplasm Metastasis; Pancreatic Polypeptide; Zollinger-Ellison Syndrome

Basal human pancreatic polypeptide (H.P.P.) concentrations have been measured in 41 pateints with Zollinger-Ellison syndrome (Z.E.S.) and in 100 controls. Basal H.P.P. concentrations in controls varied widely from less than 8 pmol/l (assay detection limit) to 313 pmol/l. In controls, but not in the Z.E.S. patients, there was a highly significant positive correlation between basal H.P.P. and age (P less than 0.01). 4 of the Z.E.S. patients (9.8%) and 3 of the controls (3%) had H.P.P. concentrations over 240 pmol/l. These findings indicate that raised basal H.P.P. concentration is an infrequent finding in patients with gastrinomas and therefore it is not a useful tumour marker.

Topics: Adult; Gastrins; Humans; Middle Aged; Pancreatic Hormones; Peptides; Zollinger-Ellison Syndrome

Gastrin release was studied in 5 hypergastrinemic patients, both during calcium infusion and EDTA infusion. In each patient, gastrin decreased in conjunction with the fall in plasma calcium, and increased during calcium infusion. Plasma gastrin and calcium levels were strongly correlated.

Topics: Achlorhydria; Adolescent; Adult; Calcium; Edetic Acid; Female; Gastrins; Humans; Hyperplasia; Infusions, Parenteral; Male; Middle Aged; Pyloric Antrum; Secretory Rate; Zollinger-Ellison Syndrome

Bromocriptine was administered to 2 subjects with gastrin-secreting tumors of the pancreas. The absorption of the drug was confirmed by a rise in growth hormone levels but no change in the elevated serum gastrin levels were observed. Bromocriptine does not appear to affect gastrin hypersecretion in the way that it influences the hypersecretion of pituitary hormones.

Topics: Adenoma; Adenoma, Islet Cell; Adult; Bromocriptine; Gastrins; Growth Hormone; Humans; Male; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

The concentration and molecular form of gastrin in urine were determined radioimmunochemically. Urine from hypergastrinaemic patients (Zollinger-Ellison syndrome and pernicious anaemia) contained gastrins corresponding to the serum components I and II. The excretion of gastrin increased with increasing gastrin concentrations in serum. Urine from six subjects with normal concentrations of gastrin in serum contained "apparent" gastrin immunoreactivity which could not be removed by specific immunoabsorption. No gastrin was detectable by gel filtration of desalted and concentrated urine from normal subjects. The apparent immunoreactivity was due partly to interference by sodium chloride. The results indicate that hypergastrinaemic patients, in contrast to normal subjects, excrete gastrins in the urine.

Topics: Anemia, Pernicious; Chromatography, Gel; Duodenal Ulcer; Gastrins; Humans; Immunosorbent Techniques; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Chemical Phenomena; Chemistry; Duodenal Ulcer; Gastrins; Humans; Hyperplasia; Immunologic Techniques; Pyloric Antrum; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Quantitative distribution of gastrin cells was evaluated in three normal human stomachs and in four stomachs from patients with Zollinger-Ellison syndrome. Cells identified by the immunoperoxidase method were counted along the entire length of five mucosal strips parallel to the axis of the lesser curvature and sampled from the posterior to the anterior walls. The number of cells per unit area (2300 microns2) decreased from the pylorus to the borderline of the gastric body from (mean +/- SEM) 50.9 +/- 12.0 to 24.2 +/- 13.0 and from 29.6 +/- 5.6 to 10.4 +/- 2.6 for control and Zollinger-Ellison syndrome, respectively, with large interindividual variations. From factorial analysis no statistical difference was found between the two groups. It is therefore suggested that the number of gastrin cell in antral mucosa may not be a significant criteria in the diagnosis of Zollinger-Ellison syndrome.

Topics: Aged; Cell Count; Chromaffin System; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Humans; Immunoenzyme Techniques; Middle Aged; Pyloric Antrum; Stomach; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Gastric Juice; Gastric Mucosa; Gastrins; Peptic Ulcer; Zollinger-Ellison Syndrome

If recurrent peptic ulceration follows partial gastrectomy with Billroth II reconstruction, retained antrum on the duodenal stump may be the culprit. Moderate hypergastrinemia and a high basal acid output (BAO) to maximal acid output (MAO) ratio on gastric analysis should alert the clinician. Careful filling of the afferent loop on barium meal or technetium 99m scanning may verify the diagnosis. The secretin provocative test may be helpful in distinguishing retained antrum from the Zollinger-Ellison syndrome by eliciting a decrease in serum gastrin levels in patients with retained antrum and an increase in serum gastrin levels in patients with Zollinger-Ellison syndrome.

Topics: Aged; Diagnosis, Differential; Gastrectomy; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Pyloric Antrum; Recurrence; Zollinger-Ellison Syndrome

The effects of calcium and secretin were studied in 8 patients with the Zollinger-Ellison syndrome and 18 patients with duodenal ulcer disease. Intravenous infusion of calcium gluconate produced marked increases in serum gastrin levels in the patients with Zollinger-Ellison syndrome (4,350 +/- 1,625 pg/mg) and very slight increases in the patients with duodenal ulcer disease (140 +/- 49 pg/ml). Secretin given as a single intravenous injection also induced marked elevations in serum gastrin in the group with the Zollinger-Ellison syndrome (4,063 +/- 1,990 pg/ml). By contrast, intravenous secretin resulted in a progressive fall in serum gastrin levels in the duodenal ulcer group (from 119 to 97 pg/mg). These results suggest that both stimuli are very useful dagnostic tools in discriminating between Zollinger-Ellison and non-Zollinger-Ellison patients. The secretin challenge test is felt to be superior to the calcium infusions because it is simpler, safer and very rarely produces false-negative or-positive results.

Topics: Adult; Calcium; Diagnosis, Differential; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Retained-antrum syndrome is a rare condition, occurring in Billroth II gastrectomised patients, in which an ulcer recurs associated with high levels of circulating gastrin. Some gastrin tests are useful to differentiate a retained antrum from a gastrinoma, but a firm diagnosis is sometimes very difficult. We have studied two cases of retained-antrum syndrome both by gastrin tests and by [99mTc] pertechnetate scintiphotography. By this method a prominent area of activity was observed on the anatomic site of the duodenal stump bottom. It appeared after 20 or 30 min and lasted for the 2 hr of observation. After surgical resection, no area of activity was observed at the scintiphotographic followup. No false positive was observed out of the more than 30 subjects studied. Scintiphotography by pertechnetate seems able to demonstrate the presence and the size of retained gastric antrum in B II gastrectomised patients with recurrent ulcer.

Topics: Diagnosis, Differential; Gastrins; Humans; Male; Middle Aged; Postgastrectomy Syndromes; Pyloric Antrum; Radionuclide Imaging; Technetium; Zollinger-Ellison Syndrome

Diagnostic procedures for the measurement of gastric acid secretion and for the differention between several types of hypergastrinemia have been improved during the last years. An intravenous dose-response curve with increasing doses of pentagastrin resulted in 30% higher MAO compared to subcutaneously administered pentagastrin (6 microgram/kg body weight). Food-stimulated gastric acid secretions can be measured by intragastric titration; this method is used mainly in clinical-physiological studies. The different forms of hypergastrinemia may be differentiated by 3 provocation tests: calciuminfusion, secretintest, glucagontest. In atypical cases of Zollinger-Ellison-Syndrome it may be necessary to perform all 3 tests.

Topics: Calcium; Dose-Response Relationship, Drug; Gastric Juice; Gastrins; Glucagon; Humans; Pentagastrin; Peptic Ulcer; Secretin; Stomach Diseases; Zollinger-Ellison Syndrome

Topics: Gastric Juice; Gastric Mucosa; Gastrins; Gluconates; Humans; Injections, Intravenous; Male; Middle Aged; Radiography; Stimulation, Chemical; Zollinger-Ellison Syndrome

Gastrin antisera were raised by immunization of rabbits or guinea pigs with synthetic human gastrin I conjugated to bovine serum albumin by carbodiimide. Radioiodination of SHG: 2-17 was performed by the chloramine T-method and by an enzymatic procedure. AE-cellulose was used to get a monoiodinated tracer hormone. Antibody reactions with the different forms of gastrin and with CCK-PZ was characterized. Precision (VK = 6-8%) and reproducibility (VK less than 15%) of the gastrin values were comparable to the insulin assay. Gastrin stimulates the parietal cell and has trophic effects on gastric mucosa. Hypergastrinaemia in combination with hypersecretion exhibits clinical significance in patients suffering from Zollinger-Ellison-syndrome or excluded antrum-syndrome which are due to autonomous gastrin release. Some findings suggest a pathogenetic role of gastrin in duodenal ulcer disease. Those disease in which gastrin determinations are of clinical value are discussed.

Topics: Animals; Duodenal Ulcer; Gastric Mucosa; Gastrins; Guinea Pigs; Humans; Rabbits; Radioimmunoassay; Stimulation, Chemical; Zollinger-Ellison Syndrome

Topics: Animals; Gastric Mucosa; Gastrins; Humans; Male; Rats; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Infusions, Parenteral; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

The effects of recent diagnostic and therapeutic advances were assessed in 65 patients with the Zollinger-Ellison syndrome (ZES). Twenty-seven patients seen between 1955 and 1970 were compared with 38 patients seen between 1971 and 1977. The earlier patients had a higher incidence of virulent ulcer disease (56% vs. 24%), other endocrinopathies (48% vs. 13%), and malignant gastrinoma (44% vs. 25%). Earlier diagnosis is the result of liberal use of serum gastrin measurements and provocative tests for gastrin release (calcium and secretin), and an increased awareness of this syndrome. Because their basal gastrin values were in a range that overlapped ordinary ulcer disease, 47% of patients encountered in recent years required provocative testing with secretin for diagnosis. If the gastrin concentration falls to normal following resection of a gastrinoma, the tumor has probably been completely removed. In our patients, gastrin measurements after total gastrectomy had no prognostic significance in regards to clinical progression or regression of the neoplasm. Of 12 patients treated with cimetidine, nine experienced symptomatic improvement, and three did not. Resection of the gastrinoma should be attempted if the lesion is solitary and located in the body or tail of the pancreas, or if it is an isolated duodenal lesion. Otherwise, total gastrectomy remains the treatment of choice. In 38 patients, total gastrectomy with Roux-en-Y esophagojejunostomy was followed by 97% survival and minimal difficulties with nutrition or dumping.

Topics: Adolescent; Adult; Aged; Calcium; Cimetidine; Female; Follow-Up Studies; Gastrectomy; Gastric Acidity Determination; Gastrins; Gastroscopy; Humans; Male; Methods; Middle Aged; Secretin; Zollinger-Ellison Syndrome

Topics: Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Neoplasm Metastasis; Werner Syndrome; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Gastrins; Gastroscopy; Humans; Male; Radiography; Radioimmunoassay; Stomach; Zollinger-Ellison Syndrome

Topics: Electrolytes; Enzymes; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Histamine; Humans; Intrinsic Factor; Pentagastrin; Pepsinogens; Peptic Ulcer; Secretory Rate; Stomach Neoplasms; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Adult; Cimetidine; Female; Gastrectomy; Gastric Juice; Gastrins; Guanidines; Humans; Peptic Ulcer; Radiography; Zollinger-Ellison Syndrome

Topics: Aged; Duodenal Neoplasms; Gastrins; Gastroscopy; Humans; Male; Zollinger-Ellison Syndrome

Topics: Biological Assay; Gastrins; Humans; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Animals; Cimetidine; Dogs; Duodenal Ulcer; Gastrins; Histamine H2 Antagonists; Humans; Zollinger-Ellison Syndrome

Topics: Female; Gastric Mucosa; Gastrins; Humans; Male; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

1. Due to their common origin from the neural crest the hormonogenic cells of the intestinal tract show similar cyto-chemical and ultra-structural characteristics. 2. Hyperplasiae and tumors of these cells lead to excessive hormone production with its consequences on the reacting organs. 3. Hormone producing tumors can be confined to one organ only, but as multiple endocrine adenomatosis they can afflict several organs. 4. Diagnosis of most hormone producing tumors is possible with the adequate radio-immunologic tests. Radiologic and endoscopic examinations can contribute to the localization of the tumor. 5. Surgical resection of the tumor or of the reacting organs impaired by the overproduction of hormones from the tumor is the indicated therapy. Medicamentous therapy is rarely successful. 6. The growth of most hormonogenic tumors is relatively slow. Rates of survival of up to 30 years have been known, even after formation of metastases of the tumor. Effects of hormone overproduction on other organs can reduce the prognosis.

Topics: Adenoma; Carcinoid Tumor; Diarrhea; Gastrectomy; Gastrins; Humans; Hypokalemia; Intestinal Neoplasms; Multiple Endocrine Neoplasia; Pancreas; Paraneoplastic Endocrine Syndromes; Syndrome; Zollinger-Ellison Syndrome

Histamine H2-receptor antagonists metiamide and cimetidine were used in the treatment of severe peptic ulceration in Zollinger-Ellison syndrome. The ulcerations were completely healed in all four patients after treatment lasting from six weeks to four-and-a-half-months. Two patients developed recurrent ulcer after the treatment had stopped, but responded to a second course. One patient developed hepatitis B during cimetidine treatment and it is possible that the course of the hepatitis was unfavourable affected by cimetidine. But no other side effects were noted nor was there a significant change in basal serum-gastrin concentration or an increase in H+ secretion. Total gastrectomy remains the treatment of choice in Zollinger-Ellison syndrome, but cimetidine should be considered if the patient refuses operation or operation is not feasible because of a poor general state.

Topics: Adult; Cimetidine; Female; Gastrins; Hepatitis B; Histamine H2 Antagonists; Humans; Male; Metiamide; Peptic Ulcer; Time Factors; Zollinger-Ellison Syndrome

Topics: Brain Neoplasms; Calcitonin; Cholesterol; Diarrhea; Endocrine Glands; Gastrins; Gastrointestinal Hormones; Histamine Release; Humans; Hypercalcemia; Neoplasms; Nutrition Disorders; Pellagra; Peptides; Serum Albumin; Thyroid Hormones; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Diagnostic Errors; Gastrins; Humans; Male; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Recurrence; Zollinger-Ellison Syndrome

Twelve patients with Zollinger-Ellison syndrome and one patient with WDHA syndrome are reviewed. Three of the Z-E patients exhibited MEA, two having hyperinsulinism and one hyperparathyroidism. Ages ranged from nine to 71 years. Diagnosis of Z-E syndrome was established from history, gastric acid secretion, radiologic studies, serum gastrin measurements and from actual tissue biopsy in 10 of the 12 patients. Total gastrectomy was performed in 8 of the 12 Z-E patients, with abolition of the ulcer diathesis in all. However, in none of our patients was there objective evidence of subsequent tumor regression. Three patients remain alive. Four died of tumor, one from post-total gastrectomy complications, one from post-subtotal gastrectomy in another hospital, two from ulcer hemorrhage, and one from electrolyte imbalance with autopsy diagnosis of Z-E tumor. A patient is recorded in detail who exhibited both hyperinsulinemia and hypergastrinemia from a malignant islet cell tumor, had the tumor "debulked" four times over a 14 year period and whose hepatic metastases were temporarily abolished by streptozotocin infusion. The question is raised regarding relationships between chronic organic hyperinsulinism and subsequent hypergastrinemia.

Topics: Adolescent; Adult; Aged; Child; Diarrhea; Female; Fluorouracil; Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Radiography; Streptozocin; Zollinger-Ellison Syndrome

The unusual finding of peptic esophagitis and duodenal ulceration in a dog was associated with a malignant pancreatic islet cell tumor producing gastrin and ACTH. The finding of a gastrinoma in a non-human species introduces the potential for developing an animal model for the study of the protean genetic biochemical, physiologic and metabolic aspects of the Zollinger-Ellison syndrome.

Topics: Adrenocorticotropic Hormone; Animals; Disease Models, Animal; Dog Diseases; Dogs; Female; Gastrins; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Anemia, Pernicious; Betazole; Cyclic AMP; Cyclic GMP; Female; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Humans; Male; Middle Aged; Pentagastrin; Peptic Ulcer; Stomach Neoplasms; Zollinger-Ellison Syndrome

A patient is presented with Zollinger-Ellison syndrome, in whom spontaneous disappearance of gastric hypersecretion and peptic ulcer disease occurred subsequent to an intercurrent illness causing acute nonspecific inflammation of the gastric mucosal lining. The dramatic clinical improvement after subsiding of the intercurrent illness was obviously linked to pronounced failure of the parietal cell mass for acid secretion and not to infarction of the gastrinoma because gastrin secretion by the tumor was unchanged.

Topics: Adenoma, Islet Cell; Adult; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Male; Pancreatic Neoplasms; Remission, Spontaneous; Secretory Rate; Zollinger-Ellison Syndrome

A case with proteinlosing gastropathy with gastric hypersecretion of H+ and pepsin as well as hypergastrinemia is presented. Zollinger-Ellison syndrome was excluded by reduction in acid secretion and serum gastrin during the observation period as well as by the effect on gastric secretion and serum gastrin after injections of secretin and glucagon.

Topics: Adult; Diagnosis, Differential; Female; Gastric Juice; Gastrins; Humans; Pepsin A; Protein-Losing Enteropathies; Radiography; Stomach; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Cimetidine; Drug Evaluation; Female; Gastric Juice; Gastrins; Guanidines; Humans; Male; Middle Aged; Pepsin A; Zollinger-Ellison Syndrome

In this study the effect of calcium infusion over 3 h without gastric aspiration on serum gastrin was determined in fifteen normal subjects, ten patients with duodenal ulcer, nine with stomal ulcer, five with total gastrectomy, six with achlorhydria and sixteen with proved or presumed Zollinger-Ellison (ZE) syndrome. Serum gastrin only rose significantly in the patients with ZE-syndrome or achlorhydria. An increase of above or below 50% of basal value seems to be a valuable criterion by which to differentiate between patients with and without ZE-syndrome. Serum gastrin levels in forty-four patients with chronic hypercalcaemia (72+/-24 pg/ml, mean+/-SD) were not significantly different from the levels in 100 normal subjects (66+/-18 pg/ml; P greater than 0.10). However, in one patient with ZE-syndrome and in two patients with achlorhydria serum gastrin values were markedly higher during chronic hypercalcaemia than during normocalcaemia. It is concluded that acute or chronic hypercalcaemia without gastric aspiration does not lead to hypergastrinaemia in the absence of ZE-syndrome or achlorhydria.

Topics: Acute Disease; Calcium; Chronic Disease; Gastrins; Humans; Hypercalcemia; Zollinger-Ellison Syndrome

In investigations with various groups of patients there was no correlation between fasting serum IRG levels and LES pressures in individual subjects with undisturbed for disturbed sphincters. After food ingestion a short phase of LES pressure increase (from 13.5 +/- 1.5 to 21.7 +/- 3.8 mm Hg) could be observed. This peak occurs during the phase of rise in gastrin level, but there was no correlation between IRG levels and LES pressure in individual cases. In patients with gastroesophageal reflux we can demonstrate a diminished release of gastrin after a test meal, but there was also a diminished capacity of the LES. In conclusion, in this investigation it has not been possible to show a clear connection in humans between serum IRG and LES function.

Topics: Esophageal Achalasia; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Pressure; Time Factors; Zollinger-Ellison Syndrome

Topics: Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Hormones; Humans; Kidney; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Evaluation Studies as Topic; Female; Gastrins; Humans; Japan; Male; Middle Aged; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Duodenal Neoplasms; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Adult; Cimetidine; Female; Gastric Juice; Gastrins; Guanidines; Humans; Male; Metiamide; Thiourea; Zollinger-Ellison Syndrome

Five patients with Zollinger-Ellison syndrome received metiamide per os in doses ranging from 600 to 1,200 mg/day for a minimum period of 2 weeks. Drug produced an inhibition of basal gastric acid secretion ranging from 5 to 100% with relief of symptoms. Survey of patients during and after metiamide course showed sometimes a prolonged antisecretory effect up to 26 days after the end of treatment or, on the contrary, a reduced drug activity in spite of increasing doses.

Topics: Adult; Dose-Response Relationship, Drug; Female; Gastric Juice; Gastrins; Humans; Male; Metiamide; Middle Aged; Secretory Rate; Thiourea; Time Factors; Zollinger-Ellison Syndrome

Antral gastrin concentration (AGC) was measured in prepyloric mucosa specimens obtained by forceps biopsy during endoscopic examination of 174 clinic and hospital patients. AGC in 32 patients who had normal endoscopic findings, the control group, varied widely from 2 to 38.6 ng gastrin/mg tissue. The mean AGC of the control patients was 14.2 +/- 1.4 (mean +/- 1 SE) ng gastrin/mg tissue. AGC was similar to control values in 18 patients with duodenal ulcer, 14.7 +/- 2.1; 12 patients with a pyloric channel or antral ulcer, 16.4 +/- 3.5; and 48 patients with miscellaneous diagnoses, 14.3 +/- 1.5. AGC was significantly less than control values in 13 patients with a ulcer in the body or fundus of the stomach, 5.9 +/- 1.5, and 4 patients with the Zollinger-Ellison syndrome, 4.9 +/- 2.4. AGC was significantly greater than in control values in 16 patients with gastritis, 25.8 +/- 4.3;22 patients with esophagitis, 23.2 +/- 3.0; and 9 patients with gastric atrophy and fasting serum hypergastrinemia 44.6 +/- 12.3. In group of 77 of these patients with heterogeneous diagnoses, meal-stimulated 3-hr integrated gastrin output was directly related to AGC (r = 0.47, P less than 0.001). In a group of 106 patients AGC was inversely related to histalogstimulated maximum acid output. The correlation was very weak (r = -0.20) but significant (P less than 0.05).

Topics: Atrophy; Biopsy; Duodenal Ulcer; Esophagitis; Gastric Mucosa; Gastrins; Gastritis; Gastroscopy; Humans; Pyloric Antrum; Stomach; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Ulcer; Fasting; Female; Gastrectomy; Gastrins; Humans; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

Basal lower esophageal sphincter (LES) pressure was measured in 6 patients with the Zollinger-Ellison syndrome (ZES) and hypergastrinemia, and in 6 patients with duodenal ulcer and normogastrinemia. Basal LES pressure in ZES patients, 17.0 +/- 3.7 (mean +/- SE) mm Hg was similar to basal LES pressure in duodenal ulcer patients, 18.3 +/- 3.5 mm Hg (P greater than 0.10). LES pressure and serum gastrin concentration were not related in the ZES patients, r = 0.03, or in the duodenal ulcer patients, r = 0.20. Intravenous infusion of calcium gluconate in ZES patients produced a marked rise in serum gastrin concentration, delta = 1580 +/- 1110 pg per ml (P less than 0.001), and a moderate but significant rise in LES pressure, delta = 5.9 +/- 0.9 mm Hg (P less than 0.05). In duodenal ulcer patients calcium infusion produced only slight rises in gastrin concentration, delta = 10 +/- 12 pg per ml, and LES pressure, delta = 2.1 +/- 0.5 mm Hg, which were not significant (P greater than 0.10). This study suggests that basal LES pressure is not regulated by blood gastrin levels in the ZES. We interpret the calcium infusion study to show that the LES pressure in patients with ZES may respond to acute changes in endogenous gastrin levels.

Topics: Adult; Aged; Calcium; Duodenal Ulcer; Esophagogastric Junction; Female; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Gastric Mucosa; Gastrins; Humans; Zollinger-Ellison Syndrome

Gastrin is a peptide hormone originating from G-cells of the antrum, the duodenum and the proximal jejunum. From extracts of gastrinomas and from sera of hypergastrinaemic subjects several gastrin molecules could be isolated which were nominated as "mini gastrin" (G13), "little gastrin" (G17), "big gastrin" (G34) and "big big gastrin". Antisera used for radioimmunological gastrin determinations should be characterized with respect to their specificity, as differeing affinity towards the various gastrins and towards CCK-PZ influences the results of the assay and thus the comparability with values of other laboratories. Gastrin is released by direct vagal stimulation of the antral G-cells and by local chemical and physical stimuli in the antrum and duodenum; probably an oxynto-pyloric reflex also exists. Gastrin stimulates in physiologic doses gastric acid secretion and, as shown in dogs and cats, reveals a trophic action on parietal cell growth. H+-secretion and gastrin release are connected by a feed back mechanism, insofar, as a decrease of intragastric pH below 3 inhibits endogenous gastrin release. Hypergastrinaemia has been demonstrated in patients with gastric anacidity or hypo-secretion, benigne pyloric stenosis, uraemia, short bowel-syndrome, gastric and duodenal ulceration and in patients with gastrinomas (Zollinger-Ellison-syndrome). Hypergastrinaemia in combination with hypersecretion exhibits clinical significance in patients suffering from Zollinger-Ellison-syndrome or excluded antrum syndrome which are due to autonomous gastrin release. The differential diagnosis between these syndromes and other diseases, in which hypergastrinaemia is not associated with gastric hypersecretion, can be achieved by several tests using calcium infusion or intravenous application of secretin and glucagon. The significance of elevated gastrin levels in patients with duodenal ulceration (DU) is pointed out. In DU-patients basal and postprandial hypergastrinaemia has been observed. In these patients gastrin release from gastric and extragastric sites is increased. In these patients hypergastrinaemia due to extragastric gastrin release could cause gastric hypersecretion at a time, when the stomach already has emptied. Furthermore parietal cell hyperplasia could be the result of chronic hypergastrinaemia.

Topics: Antibody Formation; Cross Reactions; Gastrins; Humans; Peptic Ulcer; Radioimmunoassay; Zollinger-Ellison Syndrome

There is well documented evidence indicating in-appropriately high basal gastrins in patients with duodenal ulcer disease. After stimulation by protein meals, calcium infusion, and insulin-induced hypoglycemia there appears to be an exaggerated release of gastrin in patients with duodenal ulcers compared to control subjects. Vagotomy in general tends to increase serum gastrin by decreasing acid secretion and allowing less inhibition for antral gastrin release. This increase appears less with selective vagotomy and parietal cell vagotomy compared to truncal vagotomy, suggesting vagal inhibition of gastrin release outside the antrum. Antrectomy may decrease serum gastrins by removing a major source of the hormone. However, extra antral gastrin sources, if stimulated properly, may result in little postoperative change.

Topics: Calcium; Dietary Proteins; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Hypoglycemia; Proteins; Pyloric Antrum; Pylorus; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Recent developments have led to a further appreciation of the various species of circulating gastrin and to provocative tests for the presence of the Zollinger-Ellison syndrome. Studies of serum gastrin levels, together with other studies of physiologic response, have suggested some possible roles of gastrin in the complex gastric acid hypersecretory state that frequently accompanies duodenal ulcer. Finally, investigations of exogenous and endogenous serum gastrin have provided a mechanism to examine the possible physiologic effects of this hormone.

Topics: Duodenal Ulcer; Esophagogastric Junction; Gastric Juice; Gastrins; Humans; Pressure; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastric Juice; Gastrins; Humans; Male; Methods; Middle Aged; Secretin; Zollinger-Ellison Syndrome

The influence of gastrin and somatostatin on the lower esophageal sphincter was investigated in a total of ten metabolically healthy volunteers and one patient with Zollinger-Ellison syndrome. It could be shown that only unphysiologically high concentrations of gastrin produce a rise in pressure in the lower esophageal sphincter, while somatostatin has neither an effect on the lower esophageal sphincter pressure, nor is it able to inhibit the pharmacological effect of exogenic gastrin administration. The results of this study demonstrate that normal levels of serum gastrin do not seem to have much effect of resting LES pressure, nor does somatostatin. (Gastrin, in fact, in pharmacologic dosage does have an effecton the tonicity of the lower esophageal sphincter.)

Topics: Adult; Esophagogastric Junction; Gastrins; Humans; Manometry; Pressure; Somatostatin; Zollinger-Ellison Syndrome

Topics: Adult; Aorta; Catheterization; Female; Gastrectomy; Gastrins; Humans; Lymphatic Metastasis; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Portal Vein; Vena Cava, Inferior; Zollinger-Ellison Syndrome

Twenty-four patients with postoperative recurrent peptic ulcer, presenting to a teaching hospital over a six-year period, are reviewed. The diagnosis was confirmed by endoscopy or surgery in all cases. Four patients (16-7%) were shown to have the Zollinger-Ellison syndrome and were treated successfully by total gastrectomy. This is a significantly higher incidence of Zollinger-Ellison syndrome than in previous reports. Six patients were treated medically, with one death. In the remainder, an inadequate initial operation was considered to be the cause of recurrence. Reoperation, usually involving complete vagotomy and antrectomy, was performed. There was no mortality in this group, and no patients have had further recurrence. The importance of serum gastrin studies in all patients with recurrent peptic ulcer is emphasized.

Topics: Female; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Postoperative Complications; Recurrence; Zollinger-Ellison Syndrome

Sixty-five patients with peptic ulcer disease were evaluated for gastrinoma (Zollinger-Ellison syndrome) by measuring changes in serum gastrin concentration after intravenous (i.v.) administration of calcium or secretin, or both. The presence of gastrinoma was established in all 20 patients whose serum gastrin increased by 395 pg/ml or more after i.v. calcium and in all 18 patients whose serum gastrin concentration increased by 110 pg/ml or more after i.v. secretin. The experience with these 65 patients shows that stimulation by calcium or secretin may confirm the presence of gastrinoma in cases where the diagnosis would otherwise remain obscure. Although a positive response to calcium or secretin is diagnostic for gastrinoma a negative response does not exclude this diagnosis. Stimulation with secretin is preferred for screening for gastrinoma because it is quicker and more reliable than calcium.

Topics: Adult; Aged; Calcium; Child; False Negative Reactions; False Positive Reactions; Female; Gastrins; Humans; Male; Middle Aged; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

Topics: Calcium; Cimetidine; Food; Gastrins; Gluconates; Humans; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Diagnosis, Differential; Diarrhea; Female; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Hypercalcemia; Liver Neoplasms; Multiple Endocrine Neoplasia; Neoplasm Metastasis; Zollinger-Ellison Syndrome

The mechanisms controlling secretion of glucagon and other pancreatic hormones were studied in a patient affected with multihormone-secreting islet-cell tumor. Fasting glucagon levels (3,000 pg./ml.) rose to 10 ng./ml. following arginine stimulation. While oral glucose load and intravenous glucose infusion did not suppress glucagon secretion, insulin administration induced a prompt depression in glucagon levels. Glucagon, insulin, and gastrin levels were suppressed by somatostatin while calcium infusion caused a paradoxical increase. It is suggested that only some of the stimulation-inhibition mechanisms were conserved in this case of glucagon-secreting pancreatic tumor.

Topics: Arginine; Blood Glucose; Calcium; Fatty Acids, Nonesterified; Female; Gastrins; Glucagon; Glucose; Glucose Tolerance Test; Growth Hormone; Homeostasis; Humans; Insulin; Insulin Secretion; Middle Aged; Multiple Endocrine Neoplasia; Somatostatin; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Duodenum; Feedback; Gastrins; Hydrogen-Ion Concentration; Molecular Weight; Peptic Ulcer; Stomach; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Histamine H2-receptor antagonists, including burimamide, metiamide and cimetidine, are effective antagonists of histamine-stimulated acid secretion from mammalian, avian or reptilian gastric mucosa. Acid secretion stimulated by gastrin or pentagastrin is also inhibited by these drugs, but there is disagreement about the effects of these drugs on acid secretion resulting from activation of acetylcholine receptors. Based on the pharmacological evidence possibilities of treatment by these drugs were discussed in cases with excessive stimulation of acid secretion due to high blood levels of histamine or gastrin. The positive results in several trials on Zollinger-Ellison syndrome and peptic ulcer were very impressive. Some practical problems have still to be solved, for example the appropriate phase for applying the drugs. The demonstrated clinical effectiveness, however, against peptic ulceration offers a clear alternative to surgery for many patients.

Topics: Burimamide; Gastric Juice; Gastrins; Guanidines; Histamine H2 Antagonists; Humans; Imidazoles; Metiamide; Parasympatholytics; Peptic Ulcer; Zollinger-Ellison Syndrome

The relationship between the serum gastrin and calcium concentrations has been examined in patients with multiple endocrine neoplasia type I. Variations in gastrin concentrations were induced by metiamide and secretin; calcium concentrations were altered by parathyroidectomy and by calcium infusion. Changes in the serum gastrin concentrations were not accompanied by changes in the serum calcium concentration. However, alteration of the serum calcium was accompanied by significant parallel changes in the serum gastrin. It is concluded that acute changes in the serum calcium may induce changes in the serum gastrin. Parathyroidectomy in these patients produced a fall in the serum gastrin, but the ability to produce large quantities of gastrin remains. It is postulated that the thyro-parathyroid hormones may modulate the relationship between calcium and gastrin.

Topics: Adult; Aged; Calcium; Female; Gastrins; Humans; Male; Metiamide; Middle Aged; Multiple Endocrine Neoplasia; Neoplasms, Multiple Primary; Parathyroid Neoplasms; Secretin; Zollinger-Ellison Syndrome

A patient in whom Cushing syndrome had been diagnosed at the age of 23 was found 14 years later to have subclinical diabetes mellitus, subcutaneous calcified fat tissue necroses, and hypergastrinemia suggesting Zollinger-Ellison syndrome. Histopathologic investigation revealed pancreatic adenomatosis of the glucagon producing A2-cells with accompanying B-cell hyperplasia, and hyperplasia of the adrenal cortex. The origin of the increased serum gastrin concentration in this patient is not yet known. The significance of A2-cell proliferation in Zollinger-Ellison syndrome and and in multiple endocrine adenomatosis is discussed.

Topics: Adipose Tissue; Adrenal Cortex; Adrenal Glands; Adult; Calcinosis; Cholecystectomy; Cushing Syndrome; Diabetes Complications; Gastrins; Glucagon; Humans; Hyperplasia; Islets of Langerhans; Male; Multiple Endocrine Neoplasia; Necrosis; Obesity; Pancreas; Zollinger-Ellison Syndrome

In a first step of our investigation the staining characteristics, especially the argyrophilia and metachromasia, of immunohistologically identified endocrine cells of the pancreatic islets and of the gastroduodenal mucosa were tested. These staining characteristics were then examined on insulinomas and gastrinomas. Contrary to normal B cells which generally react positively with aldehyde fuchsin and pseudoisocyanine but not argyrophilic with the Grimelius method, the neoplastic B cells give inconsistent results with conventional staining methods. Yet neoplastic B cells often show argyrophilic structures. Immunohistologically, most benign insulinomas are rich in insulin-containing cells, whereas in malignant types such cells are rare. The carcinomas, however, show a typical and distinct Grimelius argyrophilia. The tumor cells of gastrinomas are Grimelius argyrophilic and slightly metachromatic, as normal G cells, yet, contrary to A1 cells, they are only exceptionally stainable with the Hellerström method. Despite the great number of Grimelius positive tumor cells, generally only a few reacted with antigastrin serum. Nevertheless, the immunohistology is the most reliable method for the diagnosis of gastrinomas. Electron microscopic results are often difficult to interpret, since gastrinomas, as well as undifferentiated or malignant insulinomas, may predominantly contain atypical secretion granules.

Topics: Adenoma, Islet Cell; Duodenum; Gastric Mucosa; Gastrins; Humans; Immunologic Techniques; Insulin; Intestinal Mucosa; Microscopy, Electron; Staining and Labeling; Zollinger-Ellison Syndrome

Topics: Animals; Calcitonin; Cats; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hyperparathyroidism; Zollinger-Ellison Syndrome

Somatostatin inhibited gastric acid secretion significantly in three ZE patients, while serum gastrin was lowered only in two. A direct inhibition of pentagastrin-stimulated acid secretion by somatostatin was demonstrated in three healthy volunteers and four patients with duodenal ulcer disease. Somatostatin reduced betazole-stimulated gastric acid secretion to a lesser degree. The immunohistological demonstration of somatostatin-producing cells apposite to antral G-cells suggest a physiological role of somatostatin in the regulation of gastrin secretion in man.

Topics: Adolescent; Adult; Antibodies; Antibody Formation; Antigens; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Insulin; Male; Somatostatin; Zollinger-Ellison Syndrome

Using a 12-hour infusion of salmon synthetic calcitonin (S-CT), distinct and sustained inhibition of gastric acid and pepsin secretion has been demonstrated in 4 normal subjects, 3 patients with peptic ulcer disease and 3 high risk patients. In 3 patients with Zollinger-Ellison syndrome, treated in the same way, elevated serum gastrin was reduced by about 50% and acid secretion by more than 90%. In healthy volunteers oral administration of human synthetic CT (H-CT) led to reduction in basal and pentagastrin-stimulated acid and pepsin secretion by about 50%, lasting for more than 2 hours after the instillation of CT. In 4 subjects receiving CT intravenously, slight nausea and headache were registered, while there were no side effects after the oral route. Serum calcium did not change after i.v. or oral administration of CT. Wheras therapeutical applications of CT, given by i.v. route, seem to be restricted to selected cases, i.e. acute gastric ulcerations with imminent or existent bleeding, the eventual benefit or orally administered CT in peptic ulcer disease should be evaluated in controlled long-term trials.

Topics: Administration, Oral; Calcitonin; Calcium; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Pepsin A; Peptic Ulcer; Stimulation, Chemical; Time Factors; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Anemia, Pernicious; Duodenal Ulcer; Gastrins; Gastritis; Gastrointestinal Diseases; Humans; Kidney Failure, Chronic; Zollinger-Ellison Syndrome

Topics: Gastrectomy; Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

Topics: Aged; Depression, Chemical; Drug Tolerance; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Streptozocin; Time Factors; Zollinger-Ellison Syndrome

Streptozocin is of value in the treatment of malignant insulinomas, but has not previously been shown to be effective against Zollinger-Ellison tumors, which secrete gastrin. This patient's malignant gastrinoma responded to treatment with streptozocin and fluorouracil. Tumor regression was verified by the disappearance of the epigastric mass, improvement of liver function, and reduction of serum gastrin levels to one third of the pretreatment level. The patient has been in remission for more than two years and has had no further treatment since the first year.

Topics: Alkaline Phosphatase; Aspartate Aminotransferases; Drug Therapy, Combination; Fluorouracil; Gastrins; Humans; Liver Function Tests; Lymphatic Metastasis; Male; Middle Aged; Streptozocin; Zollinger-Ellison Syndrome

A patient with metastatic islet cell carcinoma of the pancreas, recurrent peptic ulcer disease, and hypergastrinemia (Zollinger-Ellison syndrome) developed symptomatic hypercalcemia and renal insufficiency; she was treated with streptozotocin after parathyroidectomy failed to control her hypercalcemia. Shortly after somewhat less than the usual recommended dose of streptozotocin was administered, the serum calcium concentration fell to near normal with complete resolution of symptoms. Seven months after therapy, mild hypocalcemia, consistent with her degree of renal impairment was noted. However, mild hypercalcemia recurred 13 months after therapy. Shortly after streptozotocin therapy, the mean serum gastrin concentration fell to near normal with radiographic disappearance of the anastomotic ulcer. At 7 and 13 months after therapy, serum gastrin levels were normal. Streptozotocin therapy was accomplished without major complications; specifically, without a detrimental effect on the creatinine clearance. Thus, although hypercalcemia in patients with pancreatic islet cell tumors is often due to associated primary hyperparathyroidism, in some patients it may be due to secretion of a hypercalcemic substance from the tumor and may respond to streptozotocin. Similarly, hypergastrinemia in patients with islet cell tumors may also respond to streptozotocin.

Topics: Calcium; Female; Gastrins; Humans; Hypercalcemia; Middle Aged; Streptozocin; Zollinger-Ellison Syndrome

What is considered to represent the fourth case of perforated jejunal ulcer in association with the Zollinger-Ellison syndrome reported in the literature is discussed. Although documented in the original paper by Zollinger and Ellison, this remains a notably rare complication. Generalized peritonitis and related pathophysiological phenomena make initial definitive correction of the ulcer diathesis an extremely riskly undertaking and ill-advised. We submit that primary ulcer resection followed by total gastrectomy when the patient becomes a more suitable operative risk is the preferred method of management. The literature would appear to support this clinical view.

Topics: Adenoma, Islet Cell; Duodenal Neoplasms; Gastrectomy; Gastrins; Humans; Jejunum; Male; Middle Aged; Peptic Ulcer Perforation; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Diarrhea; Gastrectomy; Gastrins; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Radiography; Stomach Neoplasms; Zollinger-Ellison Syndrome

A 65-year-old man with hypergastrinemia associated with the Zollinger-Ellison syndrome was found to have a duodenal "carcinoid-islet cell tumor." Gastrin levels have remained normal for more than 1 year following total gastrectomy and removal of the duodenal tumor. Immunohistochemical studies for gastrin localization revealed positive staining of the tumor and of a population of nonneoplastic G-cells in the adjacent duodenal mucosa and Brunner's glands. These results support the hypothesis that gastrinomas may arise as primary tumors from duodenal G-cells rather than from ectopic pancreatic tissue. "Carcinoidislet cell tumors," like other tumors of APUD-cell origin, may express dual biochemical functions in the form of polypeptide hormone and/or amine secretion. Their content of specific hormonal products may be predicted on the basis of sensitive histochemical and immunohistochemical techniques.

Topics: Adenoma, Islet Cell; Aged; Carcinoid Tumor; Duodenal Neoplasms; Gastrins; Humans; Male; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Animals; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Humans; Zollinger-Ellison Syndrome

Angiographic findings in one giant cell carcinoma, one cystadenocarcinoma, one poorly vascularized mucinous cystadenocarcinoma, as well as in two avascular (gastrin- and glucagon-producing) islet-cell tumors of the pancreas are described. Two hypervascularized islet-cell tumors are presented for comparison and a case of tumorous chronic pancreatitis in a child is reported because ot its rarity. The aggressiveness of the giant cell carcinoma of the pancreas was demonstrated by its expansive growth. In the case of cystadenocarcinoma angiography revealed the tumor with hepatic metastases not diagnosed at explorative laparotomy. The relative hypovascularity in the case of mucinous cystadenocarcinoma was unusual. Both avascular islet-cell tumors simulated a pancreatic pseudocyst and the final diagnosis was made only by immunoassay. Chronic pancreatitis in a child presented with marked hypervascularization.

Topics: Adenoma, Islet Cell; Adult; Aged; Angiography; Carcinoma; Celiac Artery; Chronic Disease; Contrast Media; Cystadenoma; Diagnosis, Differential; Female; Gastrins; Glucagon; Hepatic Artery; Humans; Male; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Pancreatitis; Zollinger-Ellison Syndrome

The role of prostaglandins in endocrine diarrheagenic syndromes was evaluated by measuring peripheral concentration of immunoreactive PGE and PGF in patients with non-endocrine diarrhea as well as those with the Zollinger-Ellison (Z-E) syndrome, MCT, carcinoid tumors and the WDHA syndrome. In 21 normals, PGE and PGF levels averaged 272 +/- 18 and 119 +/- 14 pg/ml, respectively. Twenty eight patients with diarrhea of non-endocrine origin (mainly inflammatory bowel disease) had levels indistinguishable from normal, i.e. 353 +/- 25 and 77 +/- 37 pg/ml, respectively. Among 29 patients with the Zollinger-Ellison syndrome (mean gastrin 6127 +/- 3267 pg/ml) only 2 had significantly elevated PGE levels; mean PGE levels, 382 +/- 32 pg/ml, were not significantly different from normal and did not correlate with either diarrhea or the serum gastrin concentration. In contrast, 18 of 22 patients with carcinoid tumors (mean blood serotonin concentration 1655 +/- 604 ng/ml; mean urinary excretion of 5 HIAA 66.8 +/- 16.7 mg/day) had elevated peripheral concentrations of PGE. The mean PGE level (1367 +/- 245 pg/ml) was significantly elevated (P less than 0.001). Nonetheless PGE levels did not correlate with diarrhea, blood concentrations of serotonin, or urinary indole excretion. MCT (mean serum calcitonin 24.5 +/- 6.3 ng/ml) was similarly associated with consistent (18/19) elevation in peripheral concentrations of PGE (mean 1922 +/- 541 pg/ml; P less than 0.001). Inthis syndrome, PGE levels were higher in patients with diarrhea and in those with markedly elevated serum thyrocalcitonin levels. Finally, 8 of 21 patients with the WDHA syndrome had increased levels of PGE. Although 13 of 17 patients had high levels of VIP (mean 8133 pg/ml), 2 patients had hyperprostaglandinemia in the face of normal peripheral concentrations of VIP. In one patient the serum PGE level was elevated prior to resection of the primary pancreatic neoplasm (9939 pg/ml) as well as the subsequent extirpation of a solitary hepatic metastasis (1063 pg/ml); following each procedure the diarrhea abated and the PGE level returned to normal. In none of these syndromes were mean PGF levels elevated. The study has documented hyperprostaglandinemia in some endocrine diarrheagenic syndromes and validated the usefullness of measurements of PGE in patients with unexplained diarrhea.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Diarrhea; Female; Gastrins; Humans; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Peptides; Secretin; Somatostatin; Zollinger-Ellison Syndrome

Topics: Adenoma; Adult; Aged; Cushing Syndrome; Gastric Juice; Gastrins; Glucagon; Humans; Hypercalcemia; Hyperinsulinism; Islets of Langerhans; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

An adequate therapy must be directed towards the cause of the recurrent ulcer. This is incomplete vagotomy in most cases, more seldom a hypergastrinemia with stasis in the antrum after insufficient drainage, in hyperparathyroidism, in hyperplasia of the antral G cells or in gastrinoma. After confirmation of the diagnosis by endoscopy, a causal diagnosis must therefore be made which includes secretion analysis and determination of the gastrin profile (feeding test, glucagon provocation test, secretion or calcium infusion). Criteria for evaluation and clinical conclusiveness are shown in examples. The indication scheme, whether revagotomy alone, resection alone or the combination of the two corrective operations should be performed is determined according to these criteria. So far, 41 patients have been operated on with good results in accordance with this graduated indication.

Topics: Gastrectomy; Gastric Juice; Gastrins; Gastroscopy; Glucagon; Humans; Hyperparathyroidism; Insulin; Peptic Ulcer; Recurrence; Vagotomy; Zollinger-Ellison Syndrome

To define the relationship between hyperparathyroidism (HPT) and gastric function, 31 patients with HPT were prospectively studied before and 2 to 25 months after parathyroidectomy. The gastrin response to a standard test meal (STM), the basal acid output (BAO), and the peak acid output (PAO) were determined. Parathormone and calcium were elevated in all patients and returned to normal following parathyroidectomy. The mean fasting gastrin concentration, mean integrated gastrin response (IGR) to feeding, mean basal acid output (BAO), and mean peak acid output (PAO) were not changed by successful parathyroidectomy. There was no significant correlation between gastrin concentration or gastrin response to feeding and gastric acid secretion. Eight of 31 HPT patients had fasting gastrin concentrations above normal preoperatively and remained so postoperatively. Hypergastrinemia in six of these eight patients could be explained by the Zollinger-Ellison (Z-E) syndrome or chronic atrophic gastritis. The hypothesis that peptic ulcer disease seen in some HPT patients is the result of calcium-induced hypergastrinemia causing gastric hypersecretion is not supported by this study.

Topics: Adolescent; Adult; Aged; Calcium; Female; Food; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Phosphorus; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Diagnosis, Differential; Duodenal Ulcer; Gastrectomy; Gastric Juice; Gastrins; Humans; Peptic Ulcer; Radioimmunoassay; Recurrence; Zollinger-Ellison Syndrome

The availability of pure intestinal hormones and the development of radioimmunoassays for their measurement has expedited research into many aspects of gastrointestinal endocrinology. A complex balance evidently exists between the different intestinal hormones and also the rest of the endocrine system. Polyendocrinopathies have been described, and, so far, two diseases due to intestinal hormone excess (Zollinger-Ellison syndrome and the syndrome of watery diarrhea, hypokalemia and achlorhydria) elucidated. It seems likely that many more gastrointestinal endocrine diseases await discovery.

Topics: Cholecystokinin; Diagnosis, Differential; Diarrhea; Digestive System; Endocrine Glands; Esophagogastric Junction; Gastrins; Gastrointestinal Hormones; Humans; Hypoglycemia; Intestinal Diseases; Intestine, Large; Pancreas; Peptic Ulcer; Prostaglandins; Pylorus; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Gastrins; Humans; Molecular Weight; Peptic Ulcer; Zollinger-Ellison Syndrome

A patient with documented ZE syndrome responded to intravenous magnesium infusion by increased gastric acid output and increased serum gastrin concentration. A patient with acid hypersecretion but no gastrinoma had no substantial alteration in acid output or serum gastrin concentration following magnesium administration. This suggests that magnesium caused gastrin to be released from a gastrinoma.

Topics: Calcium; Female; Gastric Juice; Gastrins; Humans; Infusions, Parenteral; Magnesium Sulfate; Male; Middle Aged; Stimulation, Chemical; Zollinger-Ellison Syndrome

A patient is described with recurrent peptic ulceration, evidence of hypersecretion of gastric acid and excess circulating gastrin. The preoperative differentiation between extragastric "gastrinoma" and G-cell hyperplasia of the pyloric antrum as a source for the hypergastrinaemia can be made by immunofluorescent staining of an antral biopsy for "gastrin cells", and by measuring the response of the gastric antrum to an amino acid meal or secretion infusion stimulus. The site of excessive gastrin production determines the nature of the surgery required. A classification of recurrent peptic ulceration types is suggested.

Topics: Amino Acids; Diagnosis, Differential; Gastrectomy; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Pyloric Antrum; Zollinger-Ellison Syndrome

Serum gastrin concentrations were determined after an intravenous infusion of theophylline ethylenediamine (aminophylline) in 10 patients with duodenal ulcer, 9 patients with Zollinger-Ellison syndrome, 7 control subjects and 3 patients with pernicious anemia. Increases of serum gastrin levels were observed in each group. It is concluded that an aminophylline test would not be useful in the differential diagnosis of the Zollinger-Ellison syndrome.

Topics: Anemia, Pernicious; Duodenal Ulcer; Ethylenediamines; Gastrins; Humans; Theophylline; Zollinger-Ellison Syndrome

The clinical symptomatology of the Zollinger-Ellison-syndrome, the diagnostic treatment and the surgical procedure are reviewed. The syndrome with excessive non-regulated gastrin release from the ZE-tumor is the only form of ulcer disease with importance for the surgeon. The development of a sensitive radioimmunoassay for circulating gastrin facilitated its diagnosis. The possibility of Zollinger-Ellison-syndrome should always be considered if ulcer recur after surgical procedure by simple ulcer disease. If ulcers are located at atypical sites, if multiple ulcer are found, the diagnosis of a Zollinger-Ellison-syndrome should be established by measuring serum gastrin levels.

Topics: Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Stomach Ulcer; Zollinger-Ellison Syndrome

A pathophysiological role of gastrin has been established only in the Zollinger-Ellison-Syndrome. Hypergastrinemia may be found in cases with prenicious anemia, atrophic gastritis and after all forms of vagotomy; furthermore in the excluded antrum syndrome, the short bowel syndrome, in renal insufficiency, pyloric stenoses and after oral or parenteral administration of calcium. The role of gastrin in the pathogenesis of duodenal ulcer is unknown.

Topics: Anemia, Pernicious; Duodenal Ulcer; Gastrins; Gastritis; Humans; Postgastrectomy Syndromes; Zollinger-Ellison Syndrome

Recent technics, e.g. radio-immunoassay of gastrin (MacGuigan 1968), cellular immuno-fluroescence (Polak and Pearse 1972) have modified our concepts of the physiopathology of the Zollinger-Ellison syndrome hypergastrinemia of pancreatic origin. 1. Pollak and Pearse, (1972) Ganguli, Pollak and Pearse (1974) have shown that apart from the Zollinger-Ellison syndrome of pancreatic origin (ZE type II) there are cases where the hypergastrinemia is due to hyperplasia of the antral "G" cells which secrete gastrin (ZE Tye I). Thus is raised the problem of the relationship between common peptic ulcer, "G" cell antral hyperplasia and pancreatic hypergastrinemia. 2. There exists, in the anterior part of the intestine (pancreas, duodenum, stomach, ileum) a system of neuro-humoral cells derived embryologically from the neural crest (Weichert 1967, Gorin and Leger 1969). These pluripotent cells may be the origin of digestive endocrine, or carcinoid tumours, islet cell adenomas, or gastrinomas. Thus may be explained among others the multihormonal secretion of some of these tumours and the frequently multiple sites. 3. Gastrin is secreted by the duodenal "G" cells (Watson 1974). Their physiopathological role is still unknown.

Topics: Gastrins; Humans; Intestines; Pancreas; Pancreatic Neoplasms; Stomach; Zollinger-Ellison Syndrome

Topics: Gastric Juice; Gastrins; Humans; Zollinger-Ellison Syndrome

In contrast to normal physiologic feedback suppression of serum gastrin by secretin, a paradoxic rise in the serum gastrin level has been observed in patients with gastrinoma after the administration of exogenous secretin. Exploitation of this phenomenon in the differential diagnosis of gastrinoma has been restricted by limited individual experience. Serial serum specimens for gastrin radioimmunoassay were collected from 13 patients with histologically proved gastrinoma both before and after the administration of Boot's secretin, 3 units per kilogram. Thirty-nine others with histologically proved gastrinoma who had been studied with exogenous secretin were identified in the literature. Both the peak gastrin and the integrated gastrin responses were increased after secretin administration in each of the patients in this combined series, although the magnitude of the increase was small in four patients. The absence of physiologic suppression by secretin implies neoplastic autonomy of gastrin releasing sites. While an augmented gastrin response to secretin is commonly seen in patients with gastrinoma, from a physiologic standpoint, a lack of suppression constitutes a positive secretin suppression test. Accumulated experience is consistent and suggests that this test is an important adjunt in the differential diagnosis of hypergastrinemia.

Topics: Gastrins; Humans; Secretin; Zollinger-Ellison Syndrome

The characteristics are described of an antibody (designated L6) which has virtually absolute specificity for heptadecapeptide gastrin. This antibody binds G17, but does not bind peptide fragments or molecular forms of gastrin comprising G17 with either amino acid deletions, or additions, at the carboxyl- and amino-terminals. In serum from patients with Zollinger-Ellison syndrome the only form of gastrin revealed by L6 was compatible with G17, and there was good agreement between estimated G17 concentrations in serum analyzed by gel filtration and by direct radioimmunoassay using L6. Using L6 in conjunction with antibodies specific for carboxyl- and amino-terminals of G17 it has been possible to measure concentrations of different forms of gastrin in serum of normal subjects after a meal in greater detail than previously possible. After a light meal consisting of eggs, toast, and Oxo, serum concentrations of G17 measured by L6 increased to a peak 20 min after feeding (delta gastrin, 19 pmoles per liter; n = 17). In contrast, concentration of G34 peaked at 50 min (delta gastrin, 27 pmoles per liter). Small amounts of amino-terminal fragments of G17 were present throughout the digestive period. Applying the known ratio of biological potencies of G34 and G17 for stimulation of acid secretion in man, it is estimated that G17 accounts for about 75% of the biological activity in blood after a meal, even though G34 is present in higher molar concentrations.

Topics: Adolescent; Adult; Antibodies; Antibody Specificity; Chromatography, Gel; Eating; Fasting; Female; Gastrins; Humans; Male; Peptides; Radioimmunoassay; Zollinger-Ellison Syndrome

Fasting and after meals serum gastrin levels were determined in healthy subjects and patients with different gastroenterological diseases (duodenal and gastric ulcer, hiatal hernia with gastroesophageal reflux, Billroth II gastric resection, atrophic gastritis, Zollinger-Ellison, Ménétrier, chronic calcifying pancreatitis, gastric carcinoma and lymphoma). The results pointed to the usefulness of evaluating both fasting levels and "gastrin curve" after meals as an expression of the rapidity of response of hormone-secreting gastric cells. Calculation of the I.G.O. (Integrated Gastrin Output) must also be carried out to provide a parameter from which the overall ability of G cells to secrete in response to feeding can be assessed.

Topics: Duodenal Ulcer; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Diseases; Hernia, Hiatal; Humans; Pancreatitis; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Delayed-Action Preparations; Gastric Juice; Gastrins; Humans; Somatostatin; Zollinger-Ellison Syndrome

Present knowledge about gastrointestinal peptide hormones is discussed from three points of view: (a) diagnostic significance of these hormones; (b) states characterized by over-production or deficiency of peptide hormones; (c) clinical application and perspectives of gastrointestinal hormones. The data in the literature are subjected to a critical analysis; in addition, the author's own experiments are discussed.

Topics: Anemia, Pernicious; Celiac Disease; Cholecystokinin; Duodenal Ulcer; Duodenum; Esophageal Diseases; Gastrins; Gastrointestinal Hormones; Humans; Peristalsis; Pyloric Stenosis; Secretin; Spasm; Zollinger-Ellison Syndrome

The sensitivity and reliability of the Ghosh and Schild rat stomach preparation was improved by implantation of bulky intragastric cannulae, recirculation of the perfusate and measurement of conductivity instead of pH. With these procedures, the threshold values for gastrin I were in the range of 1-2 ng. In attempts to increase the sensitivity further it was shown that neither vagotomy nor antrectomy influenced the sensitivity of the method. The threshold values were not lowered by attempts to reduce gastrin metabolism through nephroligature or small bowel resection. Although rats fitted with portacaval shunts did raise the threshold, the limited increase in sensitivity was also achieved by selecting the rats that gave an initially high response to a test dose of gastrin thus avoiding the complicated shunt operation. The assay procedure enabled statistically valid measurements of gastrin in plasma and from tumour extracts from patients suffering from the Zollinger-Ellison Syndrome to be assayed using a 2 + 2 block design.

Topics: Analysis of Variance; Animals; Body Fluids; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Intestine, Small; Male; Methods; Nephrons; Perfusion; Portacaval Shunt, Surgical; Pyloric Antrum; Rats; Tissue Extracts; Vagotomy; Zollinger-Ellison Syndrome

Topics: Colon; Colonic Neoplasms; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Gastric Mucosa; Gastrins; Humans; Nutritional Physiological Phenomena; Stomach; Zollinger-Ellison Syndrome

Topics: Adult; Diagnostic Techniques, Surgical; Female; Gastrins; Hormones, Ectopic; Humans; Pancreas; Zollinger-Ellison Syndrome

The therapeutic effectiveness of parenterally administered rabbit antigastrin antibody was evaluated in a patient with the Zollinger-Ellison syndrome who had a fasting serum gastrin level of 3020 pg/ml and a basal gastric acid secretion of 48.9 mEq/hr. Control globulin reduced gastric secretion to 32 mEq/hr. Gastrin antibody reduced it futher to 8.7 mEq/hr. Betazole hydrochloride which was given 75 min after administration of gastrin antibody stimulated acid secretion to 57.2 mEq/hr. One day later basal acid secretion was uninhibited although some antibody activity was present in the patient's serum. The results suggested that gastrin antibody acutely inhibited basal but not betazole-stimulated secretion.

Topics: Adult; Animals; Antibodies; Antibody Specificity; Binding, Competitive; Dogs; Female; Gastrins; Humans; Immunity, Maternally-Acquired; Injections, Intravenous; Rabbits; Zollinger-Ellison Syndrome

Pooling of specimens before testing may reduce the costs of expensive tests for rare conditions. This paper presents models of how test performance is degraded by such pools, and of the financial savings that pooling allows. The method of computing optimal pool size is demonstrated on a screening test and on the test for gastrin. Test characteristics that make pooling especially effective are listed.

Topics: Clinical Laboratory Techniques; Costs and Cost Analysis; False Negative Reactions; False Positive Reactions; Gastrins; Humans; Probability; Specimen Handling; Zollinger-Ellison Syndrome

Topics: Esophagogastric Junction; Fasting; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Peptic Ulcer; Pressure; Stomach Ulcer; Zollinger-Ellison Syndrome

Metiamide an histamine H2-receptors antagonist has been used to treat a case of Zollinger-Ellison syndrome characterized by a long standing diarrhea, an important gastric hypersecretion and a moderatly elevated plasma gastrin but without digestive ulceration. At the dose of 600 mg per day, Metiamide induced a complete suppression of acid secretion, an effect which lasted for 15 days after stopping the drug. Accordingly and since the only finding at time of laparotomy was a small lymph node enlarged with endocrine metastatic tissue, the stomach was left intact and Metiamide pursued. During the first 4 months of chronic administration of Metiamide, acid secretion was maintained at levels below 25 p.cent of initial values. Ulteriorly however, although dosages of Metiamide were increased, acid hypersecretion resumed and a duodenal ulcer developed. Total gastrectomy was then performed 11 months after the beginning of Metiamide. In spite of the failure of Metiamide treatment, the long term follow up of this case of Zollinger-Ellison Syndrome, allowed us to get theoretical and practical informations.

Topics: Adult; Delayed-Action Preparations; Duodenal Ulcer; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Histamine H1 Antagonists; Humans; Male; Metiamide; Middle Aged; Receptors, Drug; Secretin; Secretory Rate; Thiourea; Zollinger-Ellison Syndrome

The clinical symptomatology of the Zollinger-Ellison syndrome and the pathologic anatomy of gastrinomas are reviewed. Experience with 17 patients with the Zollinger-Ellison syndrome is presented with special reference to stimulation tests (secretin, glucagon, calcium infusion, test meal) and to localization and immunohistologic, ultrastructural, and biochemical findings in gastrinomas. Multiple hormone production by the tumors is frequent. The ultrastructure and the Sephadex G-50 gel filtration patterns of immunoreactive gastrin in sera and tumors are not uniform and are not related to localization of the tumors in the pancreas or duodenum or to the gastrin concentration. Hyperplasia of the pancreatic islets is a frequent finding in gastrinoma patients, suggesting that hypergastrinemia may stimulate islet growth.

Topics: Antigens, Neoplasm; Calcium; Chromatography, Gel; Duodenal Neoplasms; Eating; Gastrins; Glucagon; Humans; Immune Sera; Insulin; Intestinal Mucosa; Islets of Langerhans; Lymphatic Metastasis; Microscopy, Electron; Neoplasm Metastasis; Pancreatic Neoplasms; Radioimmunoassay; Secretin; Staining and Labeling; Zollinger-Ellison Syndrome

Topics: Adult; Gastrins; Humans; Imidazoles; Male; Radioimmunoassay; Sulfides; Thiourea; Zollinger-Ellison Syndrome

Topics: Gastrins; Imidazoles; Sulfides; Thiourea; Zollinger-Ellison Syndrome

The effects of human urogastrone (0-25 mug. per kg. per hour intravenously) in four male patients with proven Zollinger-Ellison syndrome (z.e.s.) and in four healthy control subjects have been studied. After urogastrone in z.e.s. patients gastric acid volume and concentration decreased and basal acid output was reduced by 50-82%; the concentrations of intrinsic factor and pepsin in gastric juice increased by 60-300%; and peak plasma-gastrin concentration increased by 127-164% of basal concentration. A significant negative correlation between increase in plasma-gastrin concentration and decrease in acid output was observed (r=-0-72, P less than 0-01). Ulcer pain was relieved 30-60 minutes after the beginning of urogastrone infusion. These results suggest that urogastrone can inhibit the endogenously stimulated acid hypersecretion in z.e.s.

Topics: Adult; Depression, Chemical; Epidermal Growth Factor; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Infusions, Parenteral; Intrinsic Factor; Male; Middle Aged; Pepsin A; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Drug Evaluation; Female; Gastrectomy; Gastrins; Humans; Streptozocin; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adult; Dehydration; Female; Gastrins; Glucagon; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Syndrome; Zollinger-Ellison Syndrome

The neurosecretory cells of the hypothalamus, and the cells of the pituitary gland and the pineal, are here grouped together as a central neuroendocrine division of the APUD series. The larger, peripheral division comprises the remainder of the original series. All the cells are proven or presumptive derivatives of neuroectoderm so that, with the present exception of the parathyroid gland and its products, peptide hormone endocrinology becomes neuroendocrinology. It follows that the pathology of the APUD cell series must be regarded as neuroendocrine and it is suggested that it can best be expressed by the term neurocristopathy (Bolande, 1974). Tumours of the series, properly neurocristomas, are preferably called apudomas because their common cytochemical (APUD) and ultrastructural characteristics provide the pathologist with a ready means of diagnosis.

Topics: Adenoma, Islet Cell; Amines; Animals; Biological Evolution; Calcitonin; Carcinoid Tumor; Cushing Syndrome; Dehydration; Ectoderm; Endocrine System Diseases; Ganglia; Gastrins; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Neoplasms, Multiple Primary; Neurosecretory Systems; Paraneoplastic Endocrine Syndromes; Peptide Biosynthesis; Secretin; Terminology as Topic; Vertebrates; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Diarrhea; Female; Gastric Juice; Gastrins; Glucose; Humans; Hypercalcemia; Male; Middle Aged; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Gastrins; Humans; Male; Pancreatic Neoplasms; Time Factors; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Calcium; Child; Diagnosis, Differential; Dogs; Female; Gastrectomy; Gastrins; Genes, Dominant; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Secretin; Sex Factors; Streptozocin; Syndrome; Zollinger-Ellison Syndrome

Foregut endocrine polypeptide-secreting APUD cells (Amine-Precursor-Uptake and Decarboxylation), in their embryologic migration from neural crest to foregut may become "arrested" in the mesoderm or in other ectopic locations. They may become hyperplastic, adenomatous or malignant. Eight illustrative patients are reported. One patient had "pancreatic hyperparathyroidism" with hypercalcemic crises, pancreatic apudocarcinoma, normal parathyroids, biologically active parathormone, but inert immunochemically to the usual parathyroid antisera. Two had gastrin-secreting malignancies in the mesoderm. Remission after excision, but eventual recurrence of the syndrome due to islet cell hyperplasia required total gastrectomy. One patient had a gastric corpus apudocarcinoma found prospectively with hypergastrinemia which required excision of the tumor. One patient had acromegaly with hypergastrinemia and antral gastrinosis treated by pituitary irradiation, One patient had the antral or intermediary type of the Zollinger-Ellison syndrome with moderate hypergastrinemia, duodenal ulcer and antral gastrinosis, treated by vagotomy and antrectomy. One patient had hyperparathyroidism with antral gastrinosis, treated by parathyroidectomy. One patient had malignant Zollinger-Ellison syndrome and developed associated thyroid parafollicular cell hyperplasia and parathyroid chief cell hyperplasia, treated by total gastrectomy and multiple endocrine excisions. These investigative observations demonstrate ectopic loci and associated hyperplasias which support the concept of migration and bizarre potentiality of polypeptide-secreting cells of the foregut.

Topics: Adenoma; Adult; Aged; Amines; Child; Decarboxylation; Endocrine System Diseases; Endoderm; Female; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Multiple Endocrine Neoplasia; Neoplasms; Pancreatic Neoplasms; Parathyroid Diseases; Parathyroid Hormone; Peptides; Stomach Neoplasms; Zollinger-Ellison Syndrome

Material from eight peptide hormone-secreting tumours, extirpated from the pancreas or from the antrum-duodenum region, was examined. Four of the patients had the clinical manifestations of the Zollinger-Ellison syndrome, two showed the features of an insulin-secreting tumour and one had a glucagonoma. Gastrin-producing cells, identified by immunohistochemistry, were found in five of the tumours. These cells displayed a varying degree of formaldehyde-ozone-induced fluorescence. This agrees with previous observations on the gastrin cell of human antral and duodenal mucosa. From model experiments, formaldehyde-ozone-induced fluorescence is thought to reflect the presence of peptides having tryptophan in the NH2-terminal position. The nature of this peptide in gastrin-producing cells is unknown.

Topics: Adult; Aged; Duodenal Neoplasms; Female; Fluorescence; Formaldehyde; Gastrins; Gastrointestinal Neoplasms; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Ozone; Pancreatic Neoplasms; Stomach Neoplasms; Tryptophan; Zollinger-Ellison Syndrome

A retrospective study was made of 34 cases of recurrent ulcer following gastric resection. Males, especially above the age of 40, were shown to be particularly susceptible. The intact vagus apparently plays the most important role in the pathogenesis. Radiological examination and endoscopy are of the greatest diagnostic importance. Truncal vagotomy must be regarded as the treatment of choice in uncomplicated recurrent ulcer. Resection procedures are indicated in perforating ulcer, gastrojejunocolic fistula, antral remains and Zollinger-Ellison syndrome.

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Germany, West; Humans; Male; Middle Aged; Peptic Ulcer; Postgastrectomy Syndromes; Recurrence; Retrospective Studies; Sex Factors; Stomach; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Calcitonin; Calcium; Gastrins; Growth Hormone-Releasing Hormone; Humans; Peptides; Secretin; Zollinger-Ellison Syndrome

In several mammals the antral gastrin cells display characteristic formaldehyde-ozone-induced fluorescence (375/500-520 nm). Such fluorescence is also given by gastrinoma cells. Gastrin granules, isolated from gastrinomas and identified by immunofluorescence and electron microscopy, were found to show intense formaldehyde-ozone-induced fluorescence.

Topics: Adult; Cytoplasmic Granules; Female; Fluorescent Antibody Technique; Formaldehyde; Gastrins; Humans; Male; Middle Aged; Ozone; Stomach; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Chromatography, Gel; Digestion; Duodenum; Gastrins; Humans; Intestinal Mucosa; Jejunum; Molecular Weight; Radioimmunoassay; Zollinger-Ellison Syndrome

In addition to the previously described molecular forms of gastrin, a new component has been found in high concentrations in the serum of 6 patients with Zollinger-Ellison syndrome. Serum was fractionated by gel filtration, and ion exchange chromatography, and the new component was identified in eluates by radioimmunoassay using an antibody with specificity for the N-terminal portion of heptadecapeptide gastrin. The precise chemical nature of the new component is not known, but its chromatographic behavior and its reactivity to various antibodies is indistinguishable from that of the natural or synthetic N-terminal 1 to 13 fragment of G-17. The new component is present in gastrinoma tumor tissue. Its concentration in serum of gastrinoma patients increases markedly when secretin is injected.

Topics: Antibodies, Neoplasm; Chemical Fractionation; Chromatography, Gel; Chromatography, Ion Exchange; Gastrins; Humans; Iodine Radioisotopes; Radioimmunoassay; Secretin; Stomach Neoplasms; Zollinger-Ellison Syndrome

50 cases of interposition of jejunal loop (32 for gastric cancer and 18 for ulcerous pathology) carried out over the last 3 years are reported. From a technical point of view and as an alternative to degastroenteroanastomosis, interposition of the loop is preferred in partial oral end-to-end on the stomach. In neoplastic lesions, Mouchet-Camey type reconstruction was adopted as a routine measure. After describing the complications of the operation and analyzing the causes, the long-term results are evaluated using absorption curves with 131-I labelled oleic acid. The excellent weight increase in the inflammatory forms, and the lack of reflow and dumping in patients subjected to total gastrectomy for cancer, confirm the value of the technique.

Topics: Adult; Aged; Dumping Syndrome; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Iodine Radioisotopes; Jejunum; Middle Aged; Neoplasm Metastasis; Oleic Acids; Peptic Ulcer; Postoperative Complications; Radioimmunoassay; Stomach Neoplasms; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Cats; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Histamine; Humans; Injections, Subcutaneous; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Zollinger-Ellison Syndrome

A patient with recurrent peptic ulceration and presumed Zollinger-Ellison syndrome whose serum gastrin concentration varied widely is reported. Two antisera, one directed predominantly against nonsulfated gastrin and the other measuring both sulfated and nonsulfated gastrin, showed that in addition to wide variation in gastrin levels, this patient secreted his gastrin predominantly in the sulfated G34 form. The possibility of variable serum gastrin levels, which may reflect either spontaneous vaiation in gastrin output from Z-E tumors or differing specificity of the antiserum utilized in the immunoassay, may be of importance in the diagnosis and management of patients with the Zollinger-Ellison syndrome. Because of gastrin heterogeneity in the Z-E syndrome, this study reinforces the concept that a broad spectrum antibody, detecting all gastrin components should be routinely used in detection of patients suspected of having the Z-E syndrome.

Topics: Betazole; Chromatography, Gel; Gastric Juice; Gastrins; Humans; Immune Sera; Insulin; Male; Middle Aged; Radioimmunoassay; Zollinger-Ellison Syndrome

Our experience with a commercially available kit for the measurement of serum gastrin has been reported. Significant non-specific interference was noted by the addition of serum contents in the assay which lead to erroneous results. Use of gastrin free serum as a diluent in the standard curve was found to improve the mean recovery of added gastrin. With this modification the procedure was evaluated for its clinical application. In 30 normal subjects, the fasting mean gastrin level was 78.7 plus or minus 31.9 (S.D.) pg/ml; in 18 of these individuals the postprandial mean level was 118.3 plus or minus 26.7 (S.D.) pg/ml. In 15 patients with pernicious anemia the mean level was 912 plus or minus 779 pg/ml; and in 4 patients with Zollinger-Ellison (ZE) syndrome the mean gastrin level was 1950 plus or minus 379 (S.D.) pg/ml. A significant rise in gastrin level was noted in patients with kidney failure during and after dialysis (p smaller than 0.05).

Topics: Anemia, Pernicious; Blood Proteins; Gastrins; Humans; Iodine Radioisotopes; Kidney Diseases; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Animals; Chromaffin System; Digestive System; Dogs; Endocrine Glands; Enterochromaffin Cells; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Intestinal Mucosa; Intestines; Microscopy, Electron; Peptic Ulcer; Rabbits; Serotonin; Stomach; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Bicarbonates; Duodenal Ulcer; Endocrine System Diseases; Esophagitis, Peptic; Esophagus; Gastric Juice; Gastrins; Humans; Hyperplasia; Intestines; Kidney Failure, Chronic; Pancreas; Pheochromocytoma; Pyloric Antrum; Stomach; Stomach Neoplasms; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Gastrins; Gastroenterostomy; Humans; Insulin; Insulin Secretion; Middle Aged; Postgastrectomy Syndromes; Pyloric Antrum; Pylorus; Vagotomy; Zollinger-Ellison Syndrome

The relative concentrations of big gastrin (G-34) and little gastrin (G-17) were compared in the sera and tumours (gastrinomas) of Zollinger-Ellison syndrome patients. Big and little gastrins were identified in all 10 serum samples and in all 10 tumour biopsies examined. In serum, G-34 (range of concentrations 58-220 000 fmol/ml) was the major form of gastrin and G-17 (22-78 000 fmol/ml) was a minor component; the mean relative abundance of G-17/[G17 + G34]) in serum was 0-18 and the mean relative abundance of G-34 was 0-82. In tumour, however, the opposite was true: G-17 (49-869 000 pmol/g) was the major component and G-34 (45-464 pmol/g) a minor component, and the relative proportions of G-17 and G-34 were 0-73 and 0-27 respectively. Following an intravenous injection of porcine secretin (2-0 U/kg) there was a rapid increase in concentration of all forms of gastrin in the blood, but the increase in G-17 was proportionately greater than that of G-34 (relative abundance of G-17 in basal serum was 0-21 compared with 0-37, five minutes after secretin). Differences in the half lives of G-17 and G-34 may partly explain their relative abundancies in serum and tumour tissue.

Topics: Antigen-Antibody Reactions; Biopsy; Chromatography, Gel; Gastrins; Half-Life; Humans; Molecular Weight; Radioimmunoassay; Zollinger-Ellison Syndrome

With better methods of diagnosis, patients will be identified earlier in the course of their disease and will often have atypical and borderline manifestations of the syndrome. Serum gastrin measurements with calcium and especially with secretin challenge will be the most important method of diagnosis. Any patient with acid hypersecretion who has a high serum gastrin level that does higher on secretin infusion should be considered to have the Zollinger-Ellison syndrome. A firm diagnosis of the Zollinger-Ellison syndrome should be made, if at all possible, prior to operation. At operation, a thorough search of the pancreas, duodenum, stomach, greater and lesser omentum and liver should be made for primary and secondary gastrinomas. If the preoperative data firmly establish the diagnosis of the Zollinger-Ellison syndrome, a total gastrectomy should be carried out even if no primary tumor is found. Similarly, a total gastrectomy should be done even if there are massive hepatic metastases. If total gastrectomy is not performed, the patient is apt to die of complications of acid hypersecretion. The only possible exceptions to the rule of always performing a total gastrectomy are in asymptomatic patients with easily excisable tumors or patients with tumors of the duodenum that are easily excisable, providing that in both instances after the excision of the tumor the output of gastric acid as measured at operation is immediately halted. All possible metastatic tumor tissue should be removed. The more tumor tissue removed, the longer the patient will survive. Metastases should be treated aggressively. They do not disappear after total gastrectomy in our experience, and they may kill patients. Patients should be followed after operation with serial measurements of serum gastrin concentrations and by hepatic scintillation scans and hepatic angiography. If hepatic metastases develop, intrahepatic artery infusions of 5-fluorouracil may slow tumor growth.

Topics: Adenocarcinoma; Adult; Aged; Angiography; Calcium; Endoscopy; Female; Gastrectomy; Gastrins; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Peptic Ulcer; Postoperative Complications; Preoperative Care; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Alcoholism; Amylases; Anemia, Pernicious; Atrophy; Bicarbonates; Gastrins; Gastritis; Humans; Pancreas; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Secretin; Zollinger-Ellison Syndrome

A collaborative study was conducted to determine interlaboratory variations in the measurement of gastrin by radioimmunoassay (RIA). A kit containing reagents for a communal RIA method, as well as test samples containing different amounts of human synthetic gastrin (SHG I) and test samples of serum from a fasting normal patient admixed with varying volumes of serum from a patient with the Zollinger-Ellison syndrome, was sent to each collaborating investigator. Each investigator was requested to measure the gastrin concentrations in test samples by means of the communal RIA method, as well as the RIA method utilized in his or her laboratory. Use of the communal RIA method resulted in no significant interlaboratory variation in the determination of gastrin concentration in SHG I test samples and a maximum two- to threefold variation in determination of gastrin serum test samples. In contrast, when individual RIA methods were used to measure gastrin concentrations, the amount of SHG I in test samples reported by one laboratory was significantly different than that reported by the other three. In addition, use of different RIA methods resulted in a 2- to 19-fold interlaboratory variation in serum gastrin measurements and the maximum variation was found when the gastrin in normal fasting serum was measured. Increased variations in results, when different RIA methods were used, may be due to differences in preparation and purification of labeled antigen, to differences in separation of bound from free hormone, and to differences in the antibodies themselves.

Topics: Gastrins; Humans; In Vitro Techniques; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Cystadenoma; Female; Gastrins; Humans; Middle Aged; Ovarian Neoplasms; Radioimmunoassay; Zollinger-Ellison Syndrome

Serum gastrin radioimmunoassay (RIA) is a sensitive and specific method suitable for measurement of circulating concentrations of this peptide hormone, which is a major regulator of gastric acid secretion. When performed under optimal conditions this RIA permits measurement of low and normal serum gastrin levels and changes that occur after physiologic stimulation. Hypergastrinemia may be secondary to atrophy of the acid-secreting gastric mucosa. This form of pypergastrinemia is appropriate and leads to no seriousequences. Hypergastrinemia associated with gastric acid hypersecretion is inappropriate. The major cause is a gastrinsecreting tumor (gastrinoma) that produces the clinical picture of the Aollinger-Ellison syndrome. The differential diagnosis of inappropraite hypergastrinemia includes antral G-cell hyperplasia and ISOLATED RETAINED ANTRUM. Accurate diagnosis of these conditions may be aided by ancillary studies including feeding, secretin, and calcium stimulation tests. Distinction among these conditions is important in planning appropriate surgical tratment.

Topics: Antibody Specificity; Arthritis, Rheumatoid; Catecholamines; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Kidney Failure, Chronic; Pentagastrin; Pheochromocytoma; Pyloric Antrum; Radioimmunoassay; Stimulation, Chemical; Stomach Neoplasms; Vagotomy; Zollinger-Ellison Syndrome

Plasma gastrin response to the intravenously administered secretin was investigated in various clinical entities. The marked increase of plasma gastrin was found in response to secretin in a case of suspected Zollinger-Ellison syndrome in contrast to various degrees of plasma gastrin decrease seen in patients with ordinary or postoperative recurrent peptic ulcer. The diagnostic value of secretin provocation test was stressed especially in relation to differentiation between Zollinger-Ellison syndrome and recurrent ulcer due to retained pyloric antrum kept away from the food-passing route, both of which are characterized by hypergastrinemia and acid hypersecretion.

Topics: Adult; Diagnosis, Differential; Gastrins; Humans; Injections, Intravenous; Male; Peptic Ulcer; Postoperative Complications; Recurrence; Secretin; Zollinger-Ellison Syndrome

The effect of exogenous glucagon and secretin on resting lower esophageal sphincter (LES) tone during endogenous hypergastrinemia was studied in 2 patients with proven Zollinger-Ellison Syndrome (ZES). Intravenous glucagon and in one patient secretin, in dosages which decrease LES pressure in normals during LES stimulation by exogenous gastrin, caused a decrease in resting LES pressure in the ZES patients. This drop in LES tone occurred both during concomitant serum gastrin rise caused by secretin and serum gastrin decline caused by glucagon. This finding suggests that the action of secretin on LES pressure may be independent on endogenous gastrin, while the glucagon effect on LES tone may be mediated through gastrin.

Topics: Adult; Esophagogastric Junction; Female; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Male; Manometry; Pentagastrin; Pressure; Secretin; Zollinger-Ellison Syndrome

Whereas 67 patients with duodenal ulcer had fasting and 30-minute postprandial mean serum gastrin levels not substantially different from 32 normal subjects, they had substantially higher fasting and histamine-stimulated gastric acid secretion. The increased acid secretion found in patients with duodenal ulcer is not caused by increased serum gastrin levels. Ten patients with recurrent ulcer, after incomplete vagotomy and gastric resection, had high gastric acid secretion and normal serum gastrin levels. Three patients with recurrent ulcer following complete vagotomy and gastric resection, but with retained antrum, had both high gastric acid secretion and high fasting and postprandial secrum gastrin levels. Three patients with Zollinger-Ellison tumors had even higher basal acid outputs and serum gastrin levels. The combination of basic gastric acid secretory studies and serum gastrin determinations may identify three causes of recurrent ulcer: incomplete vagotomy, retained antrum, and Zollinger-Ellison tumor.

Topics: Duodenal Ulcer; Fasting; Food; Gastric Juice; Gastrins; Histamine; Humans; Peptic Ulcer; Prospective Studies; Pyloric Antrum; Recurrence; Stimulation, Chemical; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

We have successfully grown six Zollinger-Ellison tumors in vitro with use of a monlayer tissue culture technique. The initial gastrin concentration in the medium varied between 0 and 100 ng per ml. Many cytoplasmic secretory granules were seen in the cells of one culture population. Gastrin secretion was stimulated by the addition of fresh medium to the culture flasks. Both the culture cells and the medium were found to contain primarily big gastrin (G-34) but smaller amounts of little gastrin (G-17) were also present. Gastrin concentration in the medium decreased with time in culture until no hormone was detected between 2 and 6 weeks, possibly because of endocrine cell dedifferentiation and an increased proportion of fibroblasts in the population.

Topics: Animals; Biopsy; Cattle; Cell Line; Chromatography, Gel; Culture Media; Culture Techniques; Cytoplasmic Granules; Endoplasmic Reticulum; Epithelial Cells; Epithelium; Gastrins; Golgi Apparatus; Humans; Microscopy, Electron; Molecular Weight; Rabbits; Radioimmunoassay; Time Factors; Trypsin; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Gastrins; Gastrointestinal Hormones; Humans; Radioimmunoassay; Zollinger-Ellison Syndrome

We have developed a sensitive, specific and reproducible radioimmunoassay for cholecystokinin (CCK) with which basal levels of CCK of between 400-800 pg/ml have been measured in normal man, in patients with diabetes and with duodenal ulcer disease, and in normal dogs. After a meal, circulating levels of CCK rose to 1000-1200 pg/ml in human subjects. Release of CCK was more rapid in diabetic and duodenal ulcer patients than in normal subjects, but elevated postprandial levels persisted much longer in normal subjects. Patients with the Zollinger-Ellison syndrome had elevated values of cholecystokinin which rose after a meal. Lack of correlation between elevated basal levels of gastrin and CCK in patients with the Zollinger-Ellison syndrome suggest that the hypercholecystokininemia may be absolute. The disappearance half-time of exogenous CCK was about 21/2 minutes in normal subjects as well as in diabetic and duodenal ulcer patients. Studies in dogs demonstrated no uptake of basal levels of cholecystokinin by the kidney; on infusion of exogenous CCK-33, the kidney extracted 43% of the total CCK presented and 56% of the integrated CCK. We conclude that: 1) circulating basal and postprandial levels of CCK may be measured in a reproducible fashion; 2) postprandial release of CCK is more rapid in diabetic and duodenal ulcer patients than in normal man; 3) the disappearance half-time of exogenous CCK in man and dogs is about 21/2 minutes; 4) the kidney is a major site for uptake of CCK.

Topics: Animals; Cholecystokinin; Diabetes Mellitus; Dogs; Duodenal Ulcer; Food; Gastrins; Half-Life; Humans; Kidney; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adult; Gastrins; Humans; Male; Peptic Ulcer; Secretin; Zollinger-Ellison Syndrome

In 36 patients with ulcer without Zollinger-Ellison-syndrome (25 patients with recurrent duodenal ulcer, 11 with an ulcus pepticum jejuni after B II-resection of the stomach) and 2 patients suffering from ulcus pepticum jejuni with an ascertained gastrinoma the secretion of acid was compared after stimulation of pentagstrin (6 mug/kg) and calcium (4 mg Ca++/kg/h). The secretion of hydrochloric acid was statistically significantly stimulated in all patients suffering from ulcer by the hypercalcaemia (increase of the serum calcium concentration from 5.0 +/- 0.3 mval/1 to 6.2 +/- 0.8 mval/1). But in patients suffering from ulcer with gastrinoma the stimulatory effect was larger than in such patients without autonomous source of gastrin: the calcium-stimulated secretion of hydrochloric acid was on the average in cases of duodenal ulcer 40% (2 to 68%), in the ulcera peptica jejuni 47% (17 to 75%), in the 4 comparative examinations of the two patients with Zollinger-Ellison-syndrome, however, always more than 100% (106 to 177%) of the pentagastrin-stimulated peak secretion. The comparative test of the pentagastrin and calcium-stimulated secretion of hydrochloric acid could be a help for the proof of autonomous places of the formation of gastrin.

Topics: Acute Disease; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hypercalcemia; Jejunum; Peptic Ulcer; Recurrence; Zollinger-Ellison Syndrome

Topics: Calcium; Gastric Juice; Gastrins; Humans; Zollinger-Ellison Syndrome

1. In a preopertive group of patients suspected of having the Zollinger-Ellison syndrome the serum gastrin and gastric acid response to calcium infusion may be highly diagnostic. 2. In a group of Zollinger-Ellison syndrome patients following total gastrectomy, the gastrin response to calcium infusion correlates well with presence or absence of tumor.

Topics: Calcium; Follow-Up Studies; Gastrectomy; Gastric Juice; Gastrins; Humans; Postgastrectomy Syndromes; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Uremia; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Female; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Zollinger-Ellison Syndrome

A survey of pathogenesis, pathobiochemistry, pathological anatomy, clinic, diagnostics and therapy of the Zollinger-Ellison-syndrome is given. The Zollinger-Ellison-syndrome is, it is true, relatively rare, but its limitation from the usual peptic ulcer has great practical consequences. The suspicion of a Zollinger-Ellison-syndrome is aroused by therapy-resistent ulcers, which in every third person are associated with a diarrhoea, by recidivations of ulcer after gastric operations and by a large basal secretion of acid. The decisive diagnostic means is the serum gastrin determination. The only promising therapy is, as a rule, the gastrectomy.

Topics: Gastric Mucosa; Gastrins; Humans; Hyperparathyroidism; Postoperative Complications; Prognosis; Stomach; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrins; Humans; Liver Neoplasms; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Topics: Adult; Duodenal Ulcer; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Hyperplasia; Pyloric Antrum; Syndrome; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Aged; Dehydration; Diagnosis, Differential; Diarrhea; Female; Fluorescent Antibody Technique; Gastrins; Humans; Hypokalemia; Islets of Langerhans; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Radioimmunoassay; Staining and Labeling; Syndrome; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Terminology as Topic; Zollinger-Ellison Syndrome

Topics: Biopsy; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hyperplasia; Meat; Peptic Ulcer; Postoperative Complications; Pyloric Antrum; Radioimmunoassay; Recurrence; Tissue Extracts; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Hyperplasia; Peptic Ulcer; Pyloric Antrum; Radioimmunoassay; Recurrence; Stomach Ulcer; Terminology as Topic; Zollinger-Ellison Syndrome

Topics: Adult; Chromaffin System; Cytological Techniques; Endoplasmic Reticulum; Enterochromaffin Cells; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Humans; Lysosomes; Male; Microscopy, Electron; Mitochondria; Staining and Labeling; Stomach; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Age Factors; Calcium; Child; Fasting; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Gastric Mucosa; Gastrins; Humans; Multiple Endocrine Neoplasia; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Diarrhea; Gastrins; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Secretin; Syndrome; Zollinger-Ellison Syndrome

Topics: Adult; Calcium; Follow-Up Studies; Gastrectomy; Gastrins; Hepatic Artery; Humans; Ligation; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Mesentery; Middle Aged; Neoplasm Metastasis; Peritoneal Neoplasms; Radiography; Radionuclide Imaging; Streptozocin; Zollinger-Ellison Syndrome

Topics: Adenoma; Adult; Cushing Syndrome; Female; Follow-Up Studies; Gastrectomy; Gastrins; Glucagon; Humans; Hyperinsulinism; Hyperparathyroidism; Male; Middle Aged; Pancreatic Neoplasms; Secretin; Streptozocin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Administration, Oral; Aged; Gastrectomy; Gastrins; Glucagon; Glucose; Glucose Tolerance Test; Humans; Injections, Intravenous; Insulin; Insulin Secretion; Liver; Liver Neoplasms; Male; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Aged; Carcinoid Tumor; Diarrhea; Female; Gastrins; Humans; Liver Neoplasms; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Biopsy; Cyclic AMP; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pentagastrin; Stimulation, Chemical; Time Factors; Zollinger-Ellison Syndrome

Topics: Adenocarcinoma; Adenoma, Islet Cell; Calcium; Child; Duodenal Diseases; Gastric Juice; Gastrins; Humans; Lymphatic Metastasis; Male; Pancreatic Neoplasms; Radiography; Zollinger-Ellison Syndrome

Topics: Gastrectomy; Gastrins; Gastroscopy; Humans; Jejunum; Peptic Ulcer; Postgastrectomy Syndromes; Pyloric Antrum; Radiography; Secretin; Zollinger-Ellison Syndrome

Topics: Digestion; Gastrins; Gastritis; Heart; Hormones, Ectopic; Humans; Peptic Ulcer; Structure-Activity Relationship; Zollinger-Ellison Syndrome

Topics: Adult; Calcium; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hypercalcemia; Injections, Intravenous; Middle Aged; Radioimmunoassay; Stomach; Time Factors; Zollinger-Ellison Syndrome

The effect of total gastrectomy on the biologic behavior of malignant gastrinomas was studied from patient data collected in the ZE tumor registry. A total of 267 patients with documented metastatic tumor had definitive gastric operations. In the 137 patients who had total gastrectomy, survival was 75% at one year, 55% at five years and 42% at ten years. In the 130 patients who had lesser gastric operations, survival was 51% at one year, 27% at five years and 18% at ten years. Deaths from progressive tumor growth occurred in 17% of the patients at risk after total gastrectomy and 30% of the patients at risk after lesser gastric operations. A subgroup of 127 patients with documented liver metastasis had definitive gastric operations. Seventythree patients with liver metastasis had total gastrectomy with survival of 68% at one year, 42% at five years and 30% at ten years. Fifty-four patients with liver metastasis had lesser gastric operations with survival of 44% at one year, 7% at five years and none at ten years. Deaths from progressive tumor growth occurred in 25% of the patients at risk after total gastrectomy and 50% of the patients at risk after lesser gastric operations. Regression of metastatic ZE tumor was clearly documented in only four patients; all had total gastrectomy. Presumptive regression of primary tumor occurred in seven patients, five had total gastrectomy. The study clearly demonstrated that total gastrectomy was the procedure of choice for malignant ZE tumors, even in the presence of widespread metastasis. The results provided indirect evidence to support a gastric feedback effect which influences growth of gastrinomas; however, the results also show that total gastrectomy furnished neither predictable nor permanent protection from subsequent tumor growth and metastasis.

Topics: Adolescent; Adult; Female; Gastrectomy; Gastrins; Humans; Liver Neoplasms; Male; Neoplasm Metastasis; Neoplasm Regression, Spontaneous; Pancreatic Neoplasms; Prognosis; Zollinger-Ellison Syndrome

In both normal volunteers and in patients with primary hyperparathyroidism, the induction of a metabolic alkalosis by infusion of sodium bicarbonate results in a decrease in serum calcium ion and in an increase of circulating parathyroid hormone concentrations. Bicarbonate infusion may serve in man as a new provocative test for release of parathyroid hormone. Furthermore, we speculate that the metabolic alkalosis which is found at times in patients with the Zollinger-Ellison syndrome and severe peptic ulcer disease may result in parathyroid gland stimulation.

Topics: Adult; Aged; Alkalosis; Bicarbonates; Calcium; Female; Gastric Juice; Gastrins; Humans; Hypercalcemia; Hyperparathyroidism; Male; Metabolic Clearance Rate; Middle Aged; Pancreatic Neoplasms; Parathyroid Hormone; Peptic Ulcer; Sodium Chloride; Zollinger-Ellison Syndrome

Topics: Child; Duodenal Neoplasms; Duodenum; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Hyperplasia; Male; Microscopy, Electron; Pancreas; Pylorus; Serotonin; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Diagnosis, Differential; Duodenal Ulcer; Fasting; Gastrectomy; Gastrins; Humans; Hyperplasia; Malabsorption Syndromes; Male; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Stomach Diseases; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Zollinger-Ellison Syndrome

Topics: Adult; Calcium; Female; Gastrins; Humans; Infusions, Parenteral; Middle Aged; Pylorus; Secretin; Time Factors; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Gastrectomy; Gastric Juice; Gastrins; Humans; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

A pair of gastrin tridecapeptides (;minigastrins') have been isolated from Zollinger-Ellison tumour tissue; they correspond to the fragment 5-17 of the heptadecapeptides isolated from the same source. In one (type II) the tyrosine residue present is sulphated, in the other (type I) it is not. The proportion of types I and II is approximately 2:1 similar to that for the ;big' gastrins and the heptadecapeptides isolated from the same source and from human antral mucosa. Both minigastrins are potent stimulants of gastric acid secretion. Immunological evidence exists to indicate that both are present as circulating forms of the hormone gastrin in patients with the Zollinger-Ellison syndrome and in fed normal subjects.

Topics: Amino Acids; Chromatography; Chromatography, Gel; Gastrins; Humans; Liver Neoplasms; Molecular Weight; Neoplasm Metastasis; Neoplasm Proteins; Peptide Fragments; Peptides; Zollinger-Ellison Syndrome

Minigastrin, a gastrin with 13 amino-acid residues, was recently isolated from tissues by Gregory and Tracy (1974). In this study, pure human natural nonsulphated minigastrin (HG-13-I) and pure human natural nonsulphated heptadecapeptide gastrin (HG-17-I) were compared with regard to acid-stimulating potency and rate of disappearance from blood. Three dogs with gastric fistulae and Heidenhain pouches were given these gastrins by continuous intravenous infusion in doses of 100, 200, 400, and 800 pmol/kg-hr. Equimolar infusion rates of HG-13-I and HG-17-I caused equimolar increases over basal of serum immunoreactive gastrin but HG-13-I- was less than half as potent as HG-17-I in stimulating acid secretion (potency ratio 0.4, 95% confidence limits 0.2 to 0.6). The half time for disappearance of HG-13-I from blood was 1.8 minutes and its volume of distribution was calculated to be 0.17 1/kg, values similar to those found for HG-17-I in an earlier study. The role of minigastrin in health and disease awaits further study.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Gastric Juice; Gastrins; Half-Life; Injections, Intravenous; Metabolic Clearance Rate; Neoplasm Proteins; Secretory Rate; Stimulation, Chemical; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Biological Assay; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Iodine Radioisotopes; Rabbits; Radioimmunoassay; Rats; Secretory Rate; Stomach Ulcer; Swine; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Gastric Juice; Gastrins; Gastrointestinal Diseases; Humans; Pentagastrin; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Gastrectomy; Gastric Juice; Gastrins; Histamine; Humans; Male; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Postoperative Care; Radioimmunoassay; Stomach Neoplasms; Zollinger-Ellison Syndrome

Topics: Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Parathyroid Glands; Renal Dialysis; Zollinger-Ellison Syndrome

Topics: Epidermal Growth Factor; Gastrectomy; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Infusions, Parenteral; Male; Pepsin A; Pyloric Antrum; Vagotomy; Zollinger-Ellison Syndrome

Topics: Calcitonin; Calcium; Depression, Chemical; Duodenal Ulcer; Eating; Gastrectomy; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hyperparathyroidism; Injections, Intravenous; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adenoma; Adult; Aged; Carcinoid Tumor; Diagnosis, Differential; Duodenal Neoplasms; Endocrine Glands; Female; Gastrins; Glucagon; Humans; Hyperparathyroidism; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Parathyroid Neoplasms; Radiography; Stomach Neoplasms; Syndrome; Zollinger-Ellison Syndrome

The apparent molecular size and charge of immunoreactive gastrin components were studied in sera from patients with pernicious anaemia or gastrinomas (the Zollinger-Ellison syndrome) by Sephadex gel filtration and aminoethylcellulose chromatography. The following serum components were distinguished: (1) a monophasic component I similar in size to proinsulin which was converted into ;little' gastrin I by trypsin digestion; (2) a biphasic component II, corresponding to ;big' gastrins I and II (Gregory and Tracy); (3) a biphasic component III corresponding to ;little' gastrins I and II (Gregory and Tracy); and (4) a biphasic component IV, corresponding to ;minigastrins' I and II (Gregory and Tracy). ;Big, big' gastrin, a plasma component found in the void volume of the Sephadex G-50 column by Yalow and Berson (1972) was undetectable in the sera investigated. A component in gastrinoma and antral mucosa extracts corresponding in size to ;big big' gastrin was detectable by the assay; the ;big big' gastrin fraction from gastrinoma tissue was heterogenous, with components of apparent MW 30 000-100 000. It is concluded that serum gastrin circulates in the form of at least four components, of which the three smaller ones are in pairs.

Topics: Anemia, Pernicious; Chromatography; Chromatography, Gel; Gastrins; Humans; Immune Sera; Insulin; Iodine Radioisotopes; Molecular Weight; Radioimmunoassay; Radioisotopes; Sodium Chloride; Sodium Isotopes; Trypsin; Zollinger-Ellison Syndrome

Topics: Adult; Calcium; Duodenal Ulcer; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Middle Aged; Radioimmunoassay; Spectrophotometry, Atomic; Zollinger-Ellison Syndrome

Topics: Acromegaly; Anemia, Pernicious; Duodenal Neoplasms; Gastric Mucosa; Gastrins; Humans; Hyperparathyroidism; Pancreatic Neoplasms; Peptic Ulcer; Pyloric Antrum; Time Factors; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Pyloric Antrum; Stomach; Stomach Diseases; Zollinger-Ellison Syndrome

Topics: Adult; Calcium; Diagnosis, Differential; Duodenal Ulcer; Female; Gastrectomy; Gastric Acidity Determination; Gastrins; Gastritis; Humans; Infusions, Parenteral; Male; Middle Aged; Peptic Ulcer; Pyloric Stenosis; Radioimmunoassay; Vagotomy; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Antibody Specificity; Cross Reactions; Dietary Proteins; Duodenal Ulcer; Gastrins; Humans; Hypoglycemia; Immune Sera; Insulin; Iodine Radioisotopes; Rabbits; Radioimmunoassay; Stomach Ulcer; Swine; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Celiac Disease; Diarrhea; Esophagitis; Female; Gastrins; Humans; Hyperparathyroidism; Male; Middle Aged; Neoplasm Metastasis; Radiography; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Age Factors; Aged; Child; Diagnosis, Differential; Female; Gastric Juice; Gastrins; Histamine; Humans; Hyperinsulinism; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Hormones; Pancreatic Neoplasms; Secretory Rate; Sex Factors; Zollinger-Ellison Syndrome

Topics: Cholecystokinin; Digestive System; Duodenal Ulcer; Endocrine Glands; Gastrins; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Paraneoplastic Endocrine Syndromes; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Barium Sulfate; Gastrins; Hematemesis; Humans; Hyperparathyroidism; Hypertension; Laparotomy; Male; Methyldopa; Multiple Endocrine Neoplasia; Peptic Ulcer; Pituitary Diseases; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Asparaginase; Child; Child, Preschool; Cushing Syndrome; Female; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Phenytoin; Secretin; Streptozocin; Zollinger-Ellison Syndrome

Topics: Adenoma; Adult; Aged; Blood Glucose; Diazoxide; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hyperparathyroidism; Hypoglycemia; Insulin; Insulin Secretion; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatectomy; Pancreatic Neoplasms; Parathyroid Neoplasms; Peptic Ulcer Perforation; Splenectomy; Zollinger-Ellison Syndrome

Sera from 15 patients with the Zollinger-Ellison syndrome were subjected to gel filtration on Sephadex G-50 superfine columns (10 x 2000 mm). The concentration of gastrin in the effluent was determined by a sensitive radioimmunoassay. Immunoreactive gastrin was eluted in four components in 14 sera. (1) Component I, eluted in the same position as proinsulin, constituted 9.7 +/- 1.2 (mean +/- SEM)% of the total immunoreactivity. (2) Component II (;big gastrin') eluted between proinsulin and insulin constituted 57.8 +/- 4.1% (mean +/- SEM) of immunoreactive gastrin. In three sera with the highest concentration of gastrin, component II appeared biphasic. (3) Component III (;little gastrin') was distributed in two peaks; the first one eluted in the same position as the heptadecapeptide gastrin II made up 17.4 +/- 2.7 (mean +/- SEM)% of the total immunoreactivity; the second one eluted in the same position as gastrin I constituted 9.5 +/- 1.3 (mean +/- SEM)%. (4) Component IV (;minigastrin') was eluted immediately before the salt peak and constituted 5.6 +/- 1.4 (mean +/- SEM)%. In one serum only components I and II were present. After incubation with trypsin all immunoreactivity in components I and II was converted to heptadecapeptide-like gastrins.The findings suggest that immunoreactive gastrin in serum from Zollinger-Ellison patients is circulating in at least four components of different molecular size.

Topics: Chromatography, Ion Exchange; Gastrins; Humans; Immunodiffusion; Insulin; Iodine Isotopes; Methods; Molecular Weight; Proinsulin; Radioimmunoassay; Sodium Isotopes; Trypsin; Zollinger-Ellison Syndrome

Topics: Adult; Animals; Autopsy; Fluorescent Antibody Technique; Gastrins; Histocytochemistry; Humans; Immune Sera; Lymph Nodes; Lymphatic Metastasis; Male; Microscopy, Electron; Pancreatic Neoplasms; Rabbits; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Duodenal Neoplasms; Follow-Up Studies; Gastrectomy; Gastric Acidity Determination; Gastrins; Humans; Hyperplasia; Lymph Node Excision; Lymphatic Metastasis; Male; Methods; Pancreatic Neoplasms; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Blood Urea Nitrogen; Calcium; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Aged; Angiography; Carcinoid Tumor; Celiac Artery; Cytoplasmic Granules; Duodenal Neoplasms; Female; Gastrins; Humans; Insulin; Insulin Secretion; Male; Mesenteric Arteries; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms; Serotonin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Radioimmunoassay; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Calcium; Endocrine Glands; Gastric Acidity Determination; Gastrins; Humans; Hyperparathyroidism, Secondary; Pancreatic Neoplasms; Secretory Rate; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Some patients with the Zollinger-Ellison syndrome appear to have hypergastrinaemia and hyperplasia of the antral G cells but no tumour. This subgroup has been classified as Zollinger-Ellison syndrome type 1. We have treated such a patient by vagotomy and antrectomy, the fasting plasma gastrin and acid secretion subsequently returning to normal.A 17-year-old male had a four-year history of duodenal ulcer. Gastric secretion tests showed acid hypersecretion. Fasting plasma gastrin was 8350 pg/ml (normal 50-170 pg/ml). At laparotomy duodenal ulceration was confirmed but no pancreatic or other tumours were found. Truncal vagotomy and antrectomy was performed with distal pancreatectomy. Immunofluorescent staining showed hyperplasia of G cells in the resected antrum but a normal pancreas and duodenum. Six months after operation he was symptom free and acid secretion was reduced by 92%. The fasting plasma gastrin at two months was <50 pg/ml. These findings suggest that type 1 Zollinger-Ellison syndrome may be a clinical entity.

Topics: Adolescent; Duodenal Ulcer; Fluorescent Antibody Technique; Gastric Juice; Gastrins; Humans; Hyperplasia; Islets of Langerhans; Male; Microscopy, Electron; Pancreas; Pyloric Antrum; Vagotomy; Zollinger-Ellison Syndrome

Topics: Animals; Diagnosis, Differential; Gastric Juice; Gastrins; Humans; Injections, Intravenous; Islets of Langerhans; Peptic Ulcer; Postgastrectomy Syndromes; Pyloric Antrum; Radionuclide Imaging; Secretin; Technetium; Zollinger-Ellison Syndrome

Topics: Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Pepsin A; Peptic Ulcer; Pyloric Stenosis; Radioimmunoassay; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Animals; Cats; Chemistry; Duodenal Ulcer; Gastrins; History, 20th Century; History, Modern 1601-; Humans; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pepsin A; Secretory Rate; Urine; Zollinger-Ellison Syndrome

Topics: Angiography; Calcium; Female; Gastrectomy; Gastrins; Humans; Lymphatic Metastasis; Male; Neoplasm Metastasis; Pancreatectomy; Prognosis; Radioimmunoassay; Spectrophotometry, Atomic; Zollinger-Ellison Syndrome

Topics: Age Factors; Calcium; Diagnosis, Differential; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Radioimmunoassay; Vagotomy; Zollinger-Ellison Syndrome

Topics: Anemia, Pernicious; Animals; Electrophoresis, Starch Gel; Gastrins; Humans; Immunization; Iodine Isotopes; Methods; Radioimmunoassay; Rats; Swine; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Recurrence; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Age Factors; Anemia, Pernicious; Charcoal; Duodenal Ulcer; Evaluation Studies as Topic; Female; Gastrins; Glycols; Heparin; Humans; Ion Exchange Resins; Male; Polymers; Radioimmunoassay; Serum Albumin; Sex Factors; Sodium Chloride; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Calcium; Dose-Response Relationship, Drug; Female; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Secretin; Zollinger-Ellison Syndrome

One hundred and fifty patients suspected of having Zollinger-Ellison syndrome were investigated. High plasma gastrin levels were found in 23 and in 16 a diagnosis of Zollinger-Ellison syndrome was confirmed. Measurement of the basal and maximal acid outputs showed that these simpler investigations have considerable value as screening tests for the selection of those patients in whom gastrin studies are indicated.

Topics: Gastric Juice; Gastrins; Histamine; Humans; Pentagastrin; Peptic Ulcer; Radioimmunoassay; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Anemia, Pernicious; Duodenal Ulcer; Ethylamines; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Humans; Insulin; Male; Middle Aged; Postoperative Complications; Pyrazoles; Recurrence; Stomach Neoplasms; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Esophagogastric Junction; Female; Gastrins; Humans; Male; Manometry; Middle Aged; Pentagastrin; Pressure; Zollinger-Ellison Syndrome

Serum gastrin was measured by radioimmunoassay in four patients with pernicious anaemia and four patients with the Zollinger-Ellison syndrome before and after the intravenous injection of 1 mg glucagon. Serum gastrin fell significantly in the patients with pernicious anaemia whilst in the patients with the Zollinger-Ellison syndrome there was a significant rise. Concomitant measurement of gastric acid output in one subject with the Zollinger-Ellison syndrome also showed a rise in acid output with glucagon. The reason for the paradoxical rise in gastrin in response to glucagon in the Zollinger-Ellison syndrome is unknown, but the response may provide a further diagnostic aid to this condition.

Topics: Aged; Anemia, Pernicious; Female; Gastric Juice; Gastrins; Glucagon; Humans; Male; Middle Aged; Radioimmunoassay; Secretory Rate; Time Factors; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Animals; Calcitonin; Carcinoma; Chickens; Depression, Chemical; Female; Gastrins; Guinea Pigs; Humans; Immune Sera; Iodine Isotopes; Male; Middle Aged; Radioimmunoassay; Stimulation, Chemical; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Animals; Chemical Phenomena; Chemistry; Chromatography, Gel; Dogs; Electrophoresis, Starch Gel; Fasting; Gastrectomy; Gastrins; Humans; Radioimmunoassay; Swine; Ultracentrifugation; Zollinger-Ellison Syndrome

Topics: Animals; Antibodies, Heterophile; Antibody Specificity; Blood Glucose; Calcium; Denervation; Dogs; Duodenal Ulcer; Food; Gastric Juice; Gastrins; Glucagon; Infusions, Parenteral; Injections, Intravenous; Male; Rabbits; Radioimmunoassay; Species Specificity; Stomach; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Duodenal Ulcer; Eating; Electric Stimulation; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Hydrogen-Ion Concentration; Parasympatholytics; Peptic Ulcer; Pyloric Antrum; Radioimmunoassay; Secretin; Secretory Rate; Stomach Ulcer; Vagus Nerve; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Aged; Anemia, Pernicious; Female; Gastrins; Humans; Male; Middle Aged; Pancreatitis; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Topics: Adult; Autopsy; Bone Neoplasms; Calcinosis; Gastrins; Humans; Hypoglycemia; Liver; Liver Neoplasms; Male; Neoplasm Metastasis; Pancreatic Neoplasms; Radiography; Stomach; Zollinger-Ellison Syndrome

Topics: Bicarbonates; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Glucagon; Humans; Immunochemistry; Intestinal Mucosa; Intestine, Small; Pancreas; Secretin; Stomach; Stomach Ulcer; Zollinger-Ellison Syndrome

Topics: Adult; Age Factors; Diarrhea; Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Radioimmunoassay; Secretory Rate; Sex Factors; Sodium Chloride; Stimulation, Chemical; Zollinger-Ellison Syndrome

Topics: Biological Assay; Diagnosis, Differential; Gastrectomy; Gastrins; Humans; Hyperplasia; Methods; Peptic Ulcer; Postoperative Care; Zollinger-Ellison Syndrome

Topics: Adenoma; Animals; Drug Tolerance; Gastric Acidity Determination; Gastric Juice; Gastrins; Histamine; Hormones, Ectopic; Humans; Hydrogen-Ion Concentration; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Pentagastrin; Radioimmunoassay; Rats; Stomach; Zollinger-Ellison Syndrome

Topics: Carcinoid Tumor; Gastric Acidity Determination; Gastric Juice; Gastrins; Hormones, Ectopic; Humans; Intestinal Mucosa; Intestine, Small; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptic Ulcer; Stomach; Zollinger-Ellison Syndrome

Topics: Animals; Drug Synergism; False Negative Reactions; Gastric Mucosa; Gastrins; Histamine; Immunization; Methacholine Compounds; Methods; Pentagastrin; Radioimmunoassay; Rats; Stimulation, Chemical; Zollinger-Ellison Syndrome

Topics: Esophagogastric Junction; Gastrins; Humans; Pressure; Zollinger-Ellison Syndrome

Topics: Chronic Disease; Gastrins; Gastritis; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Injections, Intravenous; Secretin; Time Factors; Zollinger-Ellison Syndrome

Topics: Gastrins; Histocytochemistry; Humans; Islets of Langerhans; Microscopy, Electron; Pancreatic Neoplasms; Staining and Labeling; Zollinger-Ellison Syndrome

Topics: Epithelial Cells; Gastric Mucins; Gastric Mucosa; Gastrins; Glycoproteins; Histocytochemistry; Humans; Hyperplasia; Microscopy, Electron; Pepsinogens; Staining and Labeling; Stomach; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Animals; Body Fluids; Cats; Cattle; Chromatography; Dogs; Electrophoresis; Gastrins; Humans; Peptides; Radioimmunoassay; Sheep; Swine; Tissue Extracts; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Molecular Weight; Peptides; Stomach; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Duodenal Neoplasms; Female; Gastrectomy; Gastrins; Humans; Lymphatic Metastasis; Male; Middle Aged; Radioimmunoassay; Veins; Zollinger-Ellison Syndrome