Role of serum fasting gastrin in screening for hypergastrinemic syndromes in duodenal ulcer disease.

Basal serum gastrin levels were measured in 237 patients with endoscopically confirmed duodenal ulcer and were higher than normal in 16 cases. Protein meal gastrin stimulation was performed on this group of 16 patients and on a control group of 48 patients with normal basal gastrin concentrations but high rates of either ulcer recurrence or of complications (e.g., bleeding or perforation); 21 patients from the two groups were also tested for serum gastrin inhibition with secretin. Four cases (25%) of antral G-cell hyperfunction were found in the first group, plus 1 case compatible with Zollinger-Ellison syndrome (6.2%). Only 1 case (2%) of antral G-cell hyperfunction was found among the 48 controls. These results suggest the clinical utility of routine basal gastrin measurement in screening for hypergastrinemic patients with duodenal ulcer disease.     

Potentialities of a serological method in diagnosis of atrophic gastritis

AIM: To analyse diagnostic potential of "serological gastrobiopsy" in patients with various gastroduodenal diseases. MATERIAL AND METHODS: A total of 244 patients with gastroduodenal pathology have been examined. The diagnoses made morphologically were compared with those made by the serological method. The diagnosis of duodenal ulcer, gastric ulcer, atrophic gastritis, nonatrophic gastritis was made in 155, 31, 43 and 15 patients, respectively. The type of chronic gastritis was diagnosed by the levels of gastrin-17, pepsinogen I, pepsinogen II and antibodies to Helicobacter pylori in blood serum. The diagnoses made serologically were compared with those made morphologically. RESULTS: The highest accuracy of a serological diagnosis of mucosal atrophy of the antral stomach was observed in gastric ulcer (80.6%) and duodenal ulcer (71.6%) in high sensitivity and low specificity. The accuracy of the diagnosis of gastric body mucosa atrophy in atrophic gastritis was 60.5%, in gastric ulcer--51.6%, in duodenal ulcer 58.7% in high specificity and low sensitivity. Serological diagnosis of gastric atrophy was accurate in 71.7%. In weak morphological picture of gastric body atrophy false negative serological diagnosis is possible. No false positive results occurred in diagnosis of gastric body mucosal atrophy (specificity 100%). A negative correlation was found between the severity of gastric body atrophy and pepsinogen I serum level (r = -0.380), pepsinogen I to pepsinogen II in blood serum (r = -0.392). No differences were revealed in gastrin-17 levels in the serum in different atrophy severity in the antral mucosa. CONCLUSION: "Serological gastrobiopsy"provides satisfactory accuracy of atrophic gastritis diagnosis in gastroduodenal diseases.     

Diagnosis and differential diagnosis of hypergastrinemia

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.     

Gastrin

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.     

Gastrinoma – morphological aspects

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.     

Campylobacter pylori in chronic gastritis

Altogether 301 patients with duodenal, gastric and prepyloric ulcers and non-ulcer controls were examined to study whether the Campylobacter pylori is related to ulcer itself or to coexisting chronic gastritis. Histological sections from antral and body mucosa were stained according to Warthin-Starry, Giemsa and with hematoxylin-eosin. The Campylobacter pylori was strongly associated with chronic superficial gastritis in both ulcer and non-ulcer patients and in both antral and body mucosa. No differences were found in the frequency of Campylobacter-positive cases between ulcer patients and non-ulcer controls when the comparison was made within this category of chronic gastritis (p greater than 0.05). The gastric ulcer patients have more often than non-ulcer controls the Campylobacter pylori in atrophic body gastritis (p less than 0.001). The bacteria were only occasionally seen in normal mucosa.     

Diagnostic value of secretin provocation test.

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.     

老年人消化性溃疡与慢性萎缩性胃炎的相关性研究

目的研究老年人消化性溃疡与慢性萎缩性胃炎的相关性。方法对十二指肠溃疡（DU）、胃溃疡（GU）和复合性溃疡（CU）的老年患者胃窦、胃窦胃体交界处和胃体黏膜以及慢性胃炎（CG）患者胃窦黏膜活检标本进行组织学检查,统计各自胃黏膜的萎缩、肠化生、慢性炎症、活动性和幽门螺杆菌（Hp）感染的发生率。结果 DU患者胃窦、胃窦胃体交界处和胃体黏膜的萎缩发生率分别为54.0%、8.0%和16.0%,肠化生发生率分别为19.0%、6.0%和4.0%。其胃窦黏膜肠化生的发生率明显低于相应的GU、CU或CG者。3种消化性溃疡和CG患者均存在胃窦部慢性炎症,且老年消化性溃疡患者胃体部炎症的发生率较高,其胃炎活动性以胃窦部为主,且均较CG者高。结论老年人消化性溃疡均可有胃窦部灶性萎缩和肠化生发生,但DU胃窦黏膜肠化发生率最低,这可能是老年DU患者罹患胃癌危险性较低的原因之一。     

Autoimmune atrophic gastritis with hypergastrinemia.

Elevation in fasting serum gastrin levels was found in three patients being evaluated for persistent upper abdominal pain without radiographic evidence of peptic ulcer disease. Fiberoptic endoscopy of the upper gastrointestinal tract in each patient revealed characteristic changes of chronic atrophic gastritis. Gastric biopsies showed diffuse chronic inflammation in the lamina propria, a decrease in the number of parietal cells, and "intestinalization" of gastric mucosa. Total achlorhydria was demonstrated after a maximal histalog stimulus; however, serum levels of vitamin B12 and Schilling test values were normal in all three patients. Parietal cell antibodies were found in the serum in all patients in a dilution of 1:20 to 1:80. These cases represent autoimmune (type A) chronic atrophic gastritis and should be distinguished from chronic simple (type B) gastritis, in which serum gastrin levels are normal and no parietal cell antibodies are found in the serum. Patients with autoimmune gastritis should be observed at frequent intervals for the occurrence of pernicious anemia or gastric carcinoma.     

Gastric acid regulates the release of plasma secretin in man

Abstract. Fasting plasma secretin determined in nine healthy subjects, twelve patients with active duodenal ulcer and four with Zollinger-Ellison syndrome were 3·2±0·4, 5·1±1·2 and 20·3±1·3 pmol/l respectively (mean ±SEM). Cimetidine significantly ( P <0·05) reduced levels in those with duodenal ulcer, as did gastric aspiration in the Zollinger-Ellison group. A significant correlation ( P <0·001) was found between basal acid output and mean fasting plasma secretin. After a solid meal and subsequent liquid soft drink, no sustained mean rise in plasma secretin was observed; changes in secretin appeared to coincide in time with rapid falls in duodenal pH, though little relationship could be established between the absolute level of pH and changes in plasma secretin. The mean peak post-prandial rise in plasma secretin observed after solids was significantly ( P <0·05) greater in duodenal ulcer patients than controls (9·1±1·1 versus 6·7±0·5 pmol/l) as was the mean integrated post-prandial release (1002±110 versus 710±67 pmol min^-1 l^-1). Cimetidine reduced both rises ( P <0·05) and was associated with significantly less duodenal pH readings below 4 ( P <0·001). These results suggest that gastric acid is a major release mechanism for plasma secretin both fasting and after meals but it is likely the acid load rather than absolute pH in the duodenum which determines circulating levels.     

血清胃功能检测在早期胃癌筛查中的临床应用研究

目的探讨血清胃功能检测在早期胃癌筛查中的临床应用价值。方法选取该院2015年12月至2016年12月收治的42例胃癌患者、75例胃部良性疾病患者、44例健康体检者为研究对象,所有被研究对象均进行胃镜检查,同时行镜下活检术,并按要求抽血化验,检测胃功能相关指标:胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)、PGⅠ/PGⅡ、胃泌素17(G17)及幽门螺杆菌(HP)。分析4组研究对象的血清胃功能指标的情况。结果 PGⅠ,PGⅠ/PGⅡ的表达,从低到高,分别是胃癌组、萎缩性胃炎组、胃溃疡组、浅表性胃炎组和对照组,且两两相比,差异均有统计学意义(P0.05);对照组的G17低于胃溃疡组、萎缩性胃炎组、胃癌组,胃溃疡组的G17低于胃癌组,差异有统计学意义(P0.05)。对照组的HP阳性率低于浅表性胃炎组,浅表性胃炎组低于胃溃疡组,胃溃疡组低于萎缩性胃炎组,萎缩性胃炎组低于胃癌组,差异均有统计学意义(P0.05)。结论血清胃功能检测能较好地区分胃部良性病变与恶性病变,可作为早期筛查的重要指标,且易于接受、成本低,对于检测结果阳性者,应进行胃镜下检查,以提高早期诊断率。     

Helicobacter pylori associated antral gastritis in peptic ulcer disease patients and normal healthy population of kashmir, India

Aim: To study the association of Helicobacter pylori infection with chronic antral gastritis in peptic ulcer disease patients and healthy population of Kashmir.Methods: 50 peptic ulcer patients (duodenal ulcer = 46, gastric ulcer = 2 and combined duodenal and gastric ulcer = 2) and 30 asymptomatic healthy volunteers were included in this study. Peptic ulcer was diagnosed on endoscopic examination. 4-6 punch biopsies were taken from gastric antrum in all the individuals and in case of gastric ulcer an additional biopsy was taken from the edge of the ulcer to exclude its malignant nature. Helicobacter pylori (H. pylori) organism was diagnosed using three different test methods, viz. Histology (using Giemsa Stain), Microbiology (Gram Stain) and Biochemistry (using one minute Endoscopy Room Test). Histological diagnosis of H. pylori was taken as the "gold standard" for the presence of H. pylori organism. Histological diagnosis of gastritis was made using Hematoxylin and Eosin Stain and the gastritis was classified as active chronic gastritis and superficial chronic gastritis.Results: Out of 30 peptic ulcer disease patients with associated antral gastritis, 27 (90%) were positive for H. pylori on histological examination (13 superficial chronic gastritis and 14 active chronic gastritis) whereas out of 8 healthy volunteers with histological evidence of chronic antral gastritis, H. pylori was observed in 7 individuals (87.50%) (4 active chronic gastritis and 3 superficial chronic gastritis).Conclusion: A highly significant association between H. pylori infection with chronic antral gastritis both in peptic ulcer disease patients and healthy volunteers of Kashmir was found in this study. Association between H. pylori infection and chronic gastritis was 90% in peptic ulcer group and 87.50% in healthy population (P<0.005).     

Plasma secretin concentrations in fasting and postprandial state in man.

Plasma immunoreactive secretin concentrations were determined in both healthy subjects and patients with duodenal ulcer. The modified radioimmunoassay method could detect significant increases in the plasma secretin concentrations when 0.05 N HCl was infused intraduodenally at a rate of 1.1 and 2.2 ml/min. The mean fasting plasma secretin concentration of 13 normal healthy subjects was 4.4 +/- 0.38 pg/ml which was significantly less (P less than 0.01) than that of 13 duodenal ulcer patients, 6.9 +/- 0.64 pg/ml. In both groups ingestion of a meat-containing meal resulted in significant increase in the plasma secretin concentrations. Recording of pH from proximal duodenum indicated that pH fell periodically below 4.5 during the postprandial period, indicating that only a short segment of proximal duodenum was exposed to acid after meal. The postprandial rise in plasma secretin levels was abolished when antral pH was raised 5.5 by intragastric infusion of 0.3 N NaHCO3 solution. These observations indicate that although fasting plasma secretin levels are low, the plasma secretin levels increase significantly after ingestion of a meal. This increase appears to be attributable to an increased amount of acid delivered to the proximal duodenum, and patients with duodenal ulcer were found to release more secretin during the postprandial period than normal subjects.     

Abnormal processing of antral gastrin in active duodenal ulcer disease

The concentrations of gastrins containing the active C-terminal tetrapeptide amide (mainly gastrin-34 and gastrin-17) and the N-terminal tridecapeptide fragment of gastrin-17 were measured in antral and duodenal biopsy specimens. The antral concentration of the N-terminal gastrin fragment was much higher in patients with active duodenal ulcer (33.4 +/- 6.8 nmol g-1, mean +/- SEM, n = 15) than in controls (5.6 +/- 2.9 nmol g-1, n = 10), patients with gastric ulcer (5.6 +/- 1.8 nmol g-1, n = 10) or patients with pernicious anaemia (7.7 +/- 2.5 nmol g-1, n = 6). No differences were found between the groups regarding gastrin-34 and gastrin-17 concentrations. In duodenal extracts, the N- and C-terminal gastrin concentrations were similar in all groups of patients. These data suggest that the posttranslational processing of antral gastrin is abnormal in patients with active duodenal ulcer disease.     

实时超声法测定空腹胃窦面积的临床意义

本文利用实时超声法测定了５８例健康人及５９例胃病及糖尿病病人空腹胃窦面积。结果显示，健康中国人胃窦面积为１．５２ｃｍ２±０．４３ｃｍ２，与性别、年龄、身高、体重无关，胃炎、糠尿病、活动期十二指肠溃疡病人空腹胃窦面积均有不同程度扩大，慢性胃炎伴呃逆，腹胀症状及糖尿病病人异常率为１００％。本文中有２２例病人同时做食管测压检测，结果显示溃疡病病人空腹胃窦面积与食道上、中、下段压力均无关，糖尿病、胃炎病人胃窦面积与ＬＥＳＰ呈负相关。此研究结果提示空腹胃窦面积可在某种程度上代表胃排空功能。     

Serum gastrin response to acute and chronic hypercalcaemia in man: studies on the value of calcium stimulated serum gastrin levels in the diagnosis of 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.     

A comparative assessment of gastric secretory function using a probe method and intragastric Ph-metry

To compare informative value of probing and intragastric pH-metry, relevant examination was performed in 130 patients with chronic gastritis, 132 patients with noncomplicated peptic ulcer and 50 healthy subjects. pH values obtained with probing and intragastric pH-metry did not differ significantly in defects of gastric mucosa, superficial gastritis, peptic ulcer. In apparent atrophic gastritis intragastric pH-metry detected minimal secretion of H ions in all the patients, whereas probing failed to show it. Intragastric pH-metry is useful in recognizing duodenogastric reflux and decompensated acid stomach as shown by antral basal pH (below 2.0).     

Gastrin and G-Cells in the Antral Mucosa of Patients with Pernicious Anaemia, Acromegaly and Hyperparathyroidism and in a Zollinger-Ellison Tumour of the Pancreas

Abstract. In extracts of human gastric biopsies gastrin has been estimated with an immunochemical method. In the same biopsies G-cells have been localized with an immunohistological method using peroxidase-labelled antibodies and the endocrine cells investigated electron-microscopically. Gastrin and G-cells could be found regularly in the antral mucosa and only in insignificant amounts or not at all in the fundic mucosa of six normal persons. With the same methods gastrin and G-cells could be demonstrated in the antral mucosa of rats and guinea-pigs. The gastrin content of the antral mucosa of six patients with pernicious anaemia and achlorhydria with elevated serum gastrin levels was more than 20 times higher than in the controls and the G-cells were significantly more numerous. Besides hyperplasia of the G-cells, increased secretory activity was found electron-microscopically. The gastrin release from the G-cells seems to take place mainly via intracellular dissolution of the granule content within the membranous sacs. Although the number of other endocrine cells was increased in pernicious anaemia the ultrastructural identity of the G-cells could be established by comparison with the cells of a Zollinger-Ellison tumour. This tumour contained gastrin and gave a positive immunohistological reaction for this hormone. Also, the fundic mucosa of patients with pernicious anaemia contained gastrin and G-cells, but considerably less than the antral mucosa. Hyperplasia of G-cells was found in six cases of acromegaly, four of which also had a significantly increased gastrin content of the antral mucosa. This finding suggests a trophic function of the hypophysis, especially growth hormone, on the G-cells. Hyperplasia of the G-cells in the antral mucosa of three patients with primary hyperparathyroidism and increased gastrin content in two of the three cases also suggest a trophic function of the serum calcium level on the G-cells.     

Incidence, intensity and clinical manifestations of antral gastritis in duodenal ulcer in women and their relation to Campylobacter pylori

It was established during examination of 120 women with duodenal ulcer that in 48 percent of them the clinical disease manifestations were typical. In patients with an atypical disease course, the painful syndrome was not pronounced. It was not dependent on food intake or season. 34.2 percent of the patients had, instead of pains, a feeling of heaviness in the epigastric area, heartburn and eructation depending on the antral gastritis severity. The ulcers measured 5 mm and less in 75.6 percent of the cases. Superficial antral gastritis was recognized in 69.4 and atrophic one in 25.4 percent of the patients. Secretion appeared elevated in 48.3 percent of the patients. The duodenogastral reflux was established in 68.5 percent of the cases. 75 percent of the women showed Campylobacter pyloridis in antral mucosa.     

Secretin and peptic ulcer

Eighty patients with peptic ulcer were examined by the microprecipitation test according to Hoigne. Skin tests were made in 63 and the leukocytolysis test with secretin in 39 patients who were also examined for the effect of secretin on peripheral blood cellular composition, pH of gastric juice, and for therapeutic action of the hormone. Sixty-six per cent of peptic ulcer patients showed secretin antibodies and positive skin tests, whereas 59% of patients the positive leukocytolysis test with secretin. The endogenous hormone provoked a reduction in the leukocyte, lymphocyte and neutrophil counts, raised pH of gastric juice and exerted a beneficial therapeutic action. Secretin antibodies are likely to bind the hormone and give rise to secretin deficiency. Administration of secretin has a good therapeutic effect in duodenal ulcer patients.