Serum Gastrin Determinations Research Articles

Gastric enterochromaffin-like cell changes in multiple endocrine neoplasia type 1.

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 1.5mm 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 (206pg/ml vs. 30.5pg/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.

Functional dyspesia

Dyspepsia is a functional GI disorder consisting in a wide range of symptoms. The main diagnostic challenge has been whether to perform an EGD or an abdominal US in order not to miss organic lesions, but to avoid unnecessary and sometimes invasive tests. Pepsinogen serology has been proposed as an useful non-invasive test to explore the status of the gastric mucosa, suggesting this strategy as an adequate approach in management of dyspepsia. In a primary care setting, 266 dyspeptic patients were investigated to establish the proper diagnosis. The workup included upper GI endoscopy with biopsies, a structured questionnaire including type and severity of symptoms, serological determination of serum pepsinogens, gastrin 17 and IgG against Hp. Inclusion criteria were dyspeptic symptoms (epigastric pain, nausea and/or vomiting, post prandial fullness, early satiation) lasting more than 1 year and the association between symptoms and food ingestion. Helicobacter pylori infection was present in 114 subjects, characterized by high levels of pepsinogen II and IgG against Hp. Twenty subjects were classified according with the diagnosis of chronic body atrophic gastritis. Nausea and post prandial fullness were the most frequent symptoms (48% and 41%, respectively) in the studied population, followed by epigastric pain and early satiation (37% and 26% respectively). A diagnosis of normality by serological diagnosis was found in half of patients experiencing epigastric pain and in about 60% of subjects with the three other symptoms (nausea, post prandial fullness, and early satiation). In conclusion, this experience confirms the clinical usefulness of serology in dyspepsia, contributing to correctly diagnosing CAG and H.p. infection in such patients and providing a good correlation with the clinical picture. (www.actabiomedica.it)

Combined determination of serum pepsinogen and gastrin 17 in healthy examination

Combined determination of serum pepsinogen and gastrin 17 in healthy examination

Sa1874 Incidence of Gastric Intestinal Metaplasia in Patients With Negative Helicobacter pylori

G A A b st ra ct s and / or surgery for histological examination and sub-classification of adenocarcinomas according to Lauren into diffuse, intestinal or mixed type. Fasting blood samples were collected preoperatively for determination of serum gastrin by radioimmunoassay (upper normal range 40 pM) and Helicobacter pylori (H pylori) serology. Tumor localization was determined after macroscopic and histological examination and classified as antrum, corpus and overlapping. Results: Patients with localization of the carcinoma in the gastric corpus (n=45) had significantly higher serum gastrin than patients with carcinoma localized to the antrum (n=32) (100.7±27.5 vs. 17.1±2.6 pM, p=0.004). There was no significant difference in serum gastrin between patients with intestinal type (n=49) carcinoma compared to diffuse type (n=46) carcinoma (49.7±16 vs 58.0±21 pM, p=0.33), while patients withmixed histological type (n=7) had gastrin 98.7±50.6 pM, (p=0.29 vs. intestinal type). Among patients with tumor localized to the corpus, those with diffuse type carcinoma tended to have higher serum gastrin than patients with intestinal type (131.6±61 vs. 78.4±37 pM, p =0.29). H pylori positive patients tended to have higher serum gastrin than HP negative patients (69.4±22.4 pM vs. 32.3±11.0 pM, p=0.29), but H pylori status did not differ between diffuse and intestinal type cancers (82.6% vs. 68.7% positive patients, p=0.26). Conclusions: Patients with adenocarcinomas localized to the gastric corpus had higher serum gastrin that patient with localization of carcinoma in the antrum. The histological subtype did not seem to be influenced by serum gastrin concentrations. The findings support the hypothesis that hypergastrinemia, as seen in animal models also promotes carcinogenesis in patients.

Sa2017 Blocking Peripheral Serotonin Synthesis by Telotristat Etiprate Reduces the Severity of Both Chemical- and Infection-Induced Intestinal Inflammation

G A A b st ra ct s was recorded at termination. Blood was collected for determination of serum gastrin. The histological changes in the stomachs were examined. The presence of dysplasia and carcinoma on the anterior and posterior side of the stomachs were compared, and the oxyntic mucosal thickness and neuroendocrine (chromogranin A positive) cell density were calculated. Results: Ten of fifteen animals operated by anterior vagotomy and 11 of 16 sham-operated developed hypergastrinemia. Vagotomy did not affect intragastric pH or serum gastrin. There was no difference between innervated and denervated oxyntic mucosa in dysplasia and carcinoma development. However, vagotomy resulted in lower stomach weight in hypergastrinemic animals (2.8 ± 0.26 g vs. 3.7 ± 0.39 g, p=0.027) and reduced oxyntic mucosal thickness on the anterior side (0.83 ± 0.06 mm vs. 1.13 ± 0.1 mm, p ,0.01). Vagotomy also resulted in a reduction in volume density of chromogranin A positive cells in the oxyntic mucosa (12.1 ± 1.8 % vs. 18.8 ± 3.0 %, p=0.04). Conclusions: Unilateral truncal vagotomy reduced the trophic effects of hypergastrinemia on the ECL cell and oxyntic mucosa, but did not prevent gastric carcinogenesis in female Japanese cotton rats. The effects of vagotomy on gastric carcinogenesis in animal models are conflicting and further studies in patients should be done to clarify the clinically significant effects of vagotomy.

Sa2015 Signaling in Bile Acid-Induced DNA Damage in Barrett's Esophageal Adenocarcinoma Cells

G A A b st ra ct s was recorded at termination. Blood was collected for determination of serum gastrin. The histological changes in the stomachs were examined. The presence of dysplasia and carcinoma on the anterior and posterior side of the stomachs were compared, and the oxyntic mucosal thickness and neuroendocrine (chromogranin A positive) cell density were calculated. Results: Ten of fifteen animals operated by anterior vagotomy and 11 of 16 sham-operated developed hypergastrinemia. Vagotomy did not affect intragastric pH or serum gastrin. There was no difference between innervated and denervated oxyntic mucosa in dysplasia and carcinoma development. However, vagotomy resulted in lower stomach weight in hypergastrinemic animals (2.8 ± 0.26 g vs. 3.7 ± 0.39 g, p=0.027) and reduced oxyntic mucosal thickness on the anterior side (0.83 ± 0.06 mm vs. 1.13 ± 0.1 mm, p ,0.01). Vagotomy also resulted in a reduction in volume density of chromogranin A positive cells in the oxyntic mucosa (12.1 ± 1.8 % vs. 18.8 ± 3.0 %, p=0.04). Conclusions: Unilateral truncal vagotomy reduced the trophic effects of hypergastrinemia on the ECL cell and oxyntic mucosa, but did not prevent gastric carcinogenesis in female Japanese cotton rats. The effects of vagotomy on gastric carcinogenesis in animal models are conflicting and further studies in patients should be done to clarify the clinically significant effects of vagotomy.

Long‐term, open‐label trial: safety and efficacy of continuous maintenance treatment with pantoprazole for up to 15 years in severe acid‐peptic disease

To date, the safety and tolerability of proton pump inhibitors (PPIs) have been demonstrated in studies of up to 10 years. To report on the tolerability, safety and efficacy of up to 15 years' continuous treatment with pantoprazole in patients with severe acid-peptic disease. Following healing of endoscopically confirmed peptic ulcer or reflux oesophagitis during 4-12 weeks' treatment with pantoprazole (40-80 mg/day), adult patients received open-label maintenance treatment with pantoprazole (40-160 mg/day) for up to 15 years in a single centre combined study (10-year initial study; 5-year extension study). Safety assessments were carried out using endoscopy, clinical examination, clinical laboratory investigations, serum gastrin determination, gastric mucosal histology and mucosal endocrine cell quantification. The safety set comprised 142 patients. At 12 weeks, healing rates were 95.8%. During long-term treatment, mean fasting gastrin levels rose from baseline to moderate levels throughout the study. Mean enterochromaffin-like cell density showed a moderate initial increase during the first 3 years, remaining stable thereafter. These changes were not associated with any clinically relevant changes of the gastric mucosa. Patients with successful Helicobacter pylori eradication showed long-term regression of antral and corpus gastritis during continued pantoprazole treatment. Daily pantoprazole maintenance therapy for up to 15 years for severe acid-peptic disease is effective and well tolerated, with no identified safety concerns. The longest study to date, these data provide reassuring evidence for the long-term safety of pantoprazole.

The value of corpus–antrum border determinations in highly selective vagotomy

Abstract In order to know whether the exact determination of the corpus–antrum border is of importance in highly selective vagotomy (HSV) the operation was performed on two matched groups of patients with duodenal ulcers. In group 1 (35 patients) HSV was performed using anatomical landmarks to define the distal extent of dissection. In group 2 (35 patients) HSV was performed using the same technique and then a gastrotomy was made and any remaining acid-secreting mucosa was identified using pH-metry under pentagastrin stimulation. In 22 cases secretion of acid was observed distal to the anatomically defined corpus-antrum border. In these patients afurther distal division of vagal branches was done until no acid secretion was observed. Two months and 1 year after the operation, basal acid output (BAO), pentagastrin-stimulated acid output (PAOpg), insulin-stimulated acid output (PAO1) and basal serum gastrin determinations were done and compared with the corresponding preoperative data. Our results show that despite the more extensive division of the antral vagal branches in group 2, BAO and PAOpg were similar in both groups postoperatively. Postoperative PAOI was also similar. Differences were observed, however, in postoperative serum gastrin levels–group 1 42.5 ± 6.0 pmol/l and group 281.7 ± 7.4 pmol/l 1 year after the operation. In no cases did the more extensive dissection of antral vagal branches lead to clinical or radiological gastric stasis. Thus, if the branches of the nerves of Latarjet are used as landmarks in performing HSV, in many cases vagally innervated, acid-secreting mucosa will be left in the stomach, but apparently this is quantitatively of minor importance. On the other hand, a more extensive distal vagal dissection leads to disturbingly high postoperative serum gastrin values.

Familial isolated primary hyperparathyroidism--a multiple endocrine neoplasia type 1 variant?

Familial isolated primary hyperparathyroidism (FIHP) is defined as hereditary primary hyperparathyroidism without the association of other diseases or tumors. Linkage analyses suggest that different genotypes can lead to the same phenotype of primary hyperparathyroidism. Hereditary syndromes associated with primary hyperparathyroidism are multiple endocrine neoplasia type 1 and type 2 (MEN 1 and MEN 2). In MEN 1, multiple parathyroid adenomas occur in more than 90% of the patients. Therefore, it has been suggested that FIHP could represent a variant or partial expression of MEN 1. We report on a large FIHP kindred with a MEN1 gene mutation. Nineteen family members (aged 10 to 87 years) were screened. Furthermore, statistical comparison by Fisher's exact tests of FIHP families with MEN1 gene mutations and MEN 1 families with two or more endocrinopathies was carried out to investigate genotype-phenotype correlations. Mutational analysis of leucocyte DNA was carried out by direct sequencing of the complete coding region of the MEN1 gene. Screening of MEN 1 manifestations was carried out by determination of serum calcium, phosphate, parathyroid hormone, prolactin, ACTH, cortisol, IGF-I, gastrin, glucose, insulin, glucagon, serum potassium, aldosterone, plasma renin and urinary hydroxyindoleacetic acid. We detected an in-frame deletion mutation in exon 8 of the MEN1 gene resulting in the deletion of one glutamine acid residue at position 363. It was found in eight individuals. Two of these family members (aged 42 and 60 years) were operated for primary hyperparathyroidism, and three (aged 13 to 40 years) showed mild hypercalcemia and parathyroid hormone levels within the upper normal range or slightly elevated, without any clinical symptoms. Two individuals (aged 12 and 19 years) were normocalcemic. One could not be tested. None of them had clinical evidence of other MEN 1 manifestations. Statistical comparison of the mutation types in families with FIHP and families with two or more MEN 1-associated endocrinopathies reported in other studies reveals a significant difference. In families with FIHP, missense/in-frame mutations have been found in 87.5% of cases whereas in families with tumors in various endocrine glands these mutation types occur much less frequently (21-34%, P<0.05). These studies indicate that FIHP can represent a partial MEN 1 variant and is often caused by missense/in-frame mutations.

Prevalence and causes of hypergastrinemia in primary hyperparathyroidism: a prospective study.

Gastrin levels have been reported to be often increased in patients with primary hyperparathyroidism (PHPT) considered to be caused by hypercalcemia. To determine the prevalence of increased basal gastrin and to investigate its causes, 52 consecutive patients with PHPT were studied prospectively, undergoing a clinical, biochemical, and gastric morphofunctional assessment before any parathyroid surgical procedure. This included evaluation of basal and secretin-stimulated gastrin, basal and pentagastrin-stimulated gastric acid secretion, upper gastrointestinal endoscopy, with histological evaluation for gastritis and Helicobacter pylori infection. Twenty of the 52 PHPT patients (38.5%) had increased fasting gastrin. Further investigation allowed us to clearly demonstrate the causes of hypergastrinemia in 16 of these 20 patients. In 7 of 20 (35%), hypergastrinemia was caused by gastric fundus atrophy; in 3 patients (15%), Zollinger-Ellison syndrome with Multiple Endocrine Neoplasia type I was diagnosed; whereas in another 20% of patients, mild hypergastrinemia was ascribed to Helicobacter pylori gastritis. Finally, in 2 patients, additional clinical history revealed an occasional use of the gastric antisecretory drug omeprazole a few days before the serum gastrin determination. This study shows that the hypercalcemic status per se is not sufficient to produce an increase in fasting gastrin levels. Furthermore, gastric fundus atrophy, and not gastrinoma, is the major cause of relevant (>160 pg/mL) hypergastrinemia.

Prospective study of the value of serum chromogranin A or serum gastrin levels in the assessment of the presence, extent, or growth of gastrinomas

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.

Prospective study of the value of serum chromogranin A or serum gastrin levels in the assessment of the presence, extent, or growth of gastrinomas

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. Cancer 1999;85:1470–83. © 1999 American Cancer Society.

Enterochromaffin cell density in the gastric mucosa of patients with chronic renal failure.

Thirty patients with chronic renal failure (CRF) and 30 age- and sex-matched controls were assessed for gastrointestinal diseases by gastroscopy, serum gastrin determination, and routine clinical and laboratory evaluation. Biopsy specimens from their gastric oxyntic mucosa were immunohistochemically stained with monoclonal antibodies against serotonin (5-hydroxytryptamine) and chromogranin A, the latter staining all gastric endocrine cells, the former disclosing serotonin-containing enterochromaffin (EC) cells only. The average EC cell density (cells/mm2) in the CRF patients was significantly lower than in the controls: 2.6 vs 12.9 (p = 0.0005). The EC cell counts also correlated negatively with serum gastrin values (p = 0.0031). The densities of the chromogranin-positive cells did not differ between CRF patients (74 cells/mm2) and controls (76 cells/mm2) (p = 0.7559). We conclude that, in addition to the previously known findings of hypoacidity, persistent hypergastrinaemia, and G and parietal cell hyperplasia, CRF also reduces the number of oxyntic EC cells. The negative correlation between EC cell density and serum gastrin levels reflects the complex interplay between different endocrinological activities in the gastrointestinal tract.

Omeprazole Therapy in Resistant Reflux Disease

Letters1 February 1995Omeprazole Therapy in Resistant Reflux DiseaseJames W. Freston, MDJames W. Freston, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-3-199502010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Wright and Sarich's recommendation to reserve long-term omeprazole therapy for patients with severe, erosive esophageal disease who cannot be managed with other available therapies would be reasonable if the alternative long-term therapies for less severe disease were equally efficacious, safe, and cost-effective. This recommendation, however, would exclude promotility drugs (because of their reduced efficacy and unknown long-term safety) and histamine-2-receptor antagonists in standard doses (because of their reduced efficacy) and in high doses (because of probable reduced efficacy, unknown long-term safety, and increased cost compared with omeprazole).The combination of serum gastrin determinations every 3 months and yearly ...

Assessment and prediction of long-term cure in patients with the Zollinger-Ellison syndrome: the best approach.

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.

Chronic endogenous hypergastrinemia in humans: Evidence for a mitogenic effect on the colonic mucosa

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Misdiagnosis of the Zollinger-Ellison syndrome due to hyperlipidemia

Most authorities feel that diagnosis of the Zollinger-Ellison syndrome is established when the serum gastrin level is > 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 > 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.

Role of the proximal duodenum in gastrin regulation following antrectomy.

Antrectomy is accepted as the most effective surgical treatment of recurrent duodenal ulcer after complete vagotomy. Although antrectomy is aimed at reducing serum gastrin levels, both human and experimental reports seem to indicate that gastrin concentrations may be unchanged following this operation. The probable source of gastrin has been considered to be the proximal third of the duodenum, since at this level increased tissue gastrin concentrations were found after antrectomy. The present study was carried out in order to gain insight into the mechanism by which the duodenum may compensate for the removal of the antrum. Forty white rats were randomly divided into two equal groups and underwent antrectomy with gastroduodenostomy or simple laparotomy. Three to four months after surgery, serum gastrin determinations were carried out by radioimmunoassay both in fasted and freely fed rats. The duodenum was then removed and its proximal third was used for G cell counts (immunoperoxidase method) and for assessment of G cell cytoplasmic granule distribution (electron-microscopic examination). Antrectomy significantly increased fasting serum gastrin levels (p less than 0.01), while it completely abolished the gastrin response to food ingestion (p less than 0.001). In antrectomized rats, the duodenal G cell number was significantly higher than in control rats (p less than 0.001), whilst the G cell cytoplasmic granule number remained unchanged. In conclusion, the present study indicates that in the rat the proximal duodenum increases its content of tissue gastrin following antrectomy mainly by enhancing the regional G cell density.

Upper gastrointestinal findings in chronic renal failure.

Twenty-nine patients with chronic renal failure were examined both during the predialytic stage and after active treatment (dialysis, transplantation) for upper GI diseases. They underwent a gastric dose-response secretion test, gastroduodenoscopy, radiologic upper GI series, and fasting serum gastrin determination. Upper GI diseases increased in the active treatment stage. At the time of examination, patients with these diseases had a positive ulcer history, duodenitis, duodenogastric reflux, and blood group O more often in the predialytic stage. Their stimulation sensitivity to pentagastrin and their acid secretion capacity were greater, and they were less achlorhydric. Their fasting serum gastrin level was also lower. They had less endoscopically discovered gastritis, but microscopically, with regard to gastritis, they did not differ from those who did not develop upper GI complications. In conclusion, in chronic renal failure upper GI findings increase after the active treatment. Secretion tests and endoscopy performed before active treatment give an indication of those who will develop upper GI complications during active treatment.

624 SERUM GASTRIN RESPONSE TO INTRAGASTRIC PROTEIN AND CYSTEINB IN NEONATAL SWINE

Previous work has shown a decreased gastrin release in neonatal humans and swine in response to intragastric protein. To further study gastrin release in neonatal swine, serum gastrin determinations were made following intragastric instillation of protein and the amino acid cysteine, known to release antral gastrin in adult animals. Six animals, less than 48 hours of age, had catheters placed in the femoral and portal veins. In three animals, intragastric Sustagen (1.7 gm protein/kg) was followed by intragastric cysteine (100mM, pH 7.4 at 10 cc/kg), while three received cysteine. Simultaneous femoral and portal venous samples were analyzed for gastrin at 1, 5, 15, 30, 45 and 60 minutes. The simultaneous femoral and portal vein gastrins did not differ statistically at any time. Basal gastrin was elevated in all animals when compared to adult values (p<0.1). Following intragastric cysteine infusion, there was no significant elevation in gastrin in the portal (317 vs 264 pg/ml) or femoral (253 vs 254 pg/ml) veins. After protein challenge with Sustagen, there was a delayed, but significant, elevation in gastrin in portal and femoral samples at 30, 45 and 60 minutes (386 vs 573 pg/ml P.V. and 411 vs 569 pg/ml F.V.) (p<0.5). The results of these studies indicate a significant alteration in the release of gastrin in response to intragastric amino acids in the neonatal swine when compared to adult animals.