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Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users. Thirty-two recruited patients, who received LDA (100 mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20 mg/day) and 17 patients additionally receiving vonoprazan (10 mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured. Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p

Backgrounds: Compared to proton pump inhibitors, vonoprazan exerts a greater inhibitory effect on gastric acid secretion and is useful for treating acid-related diseases, such as gastro-esophageal reflux disease. However, there is a problem that vonoprazan causes hypergastrinemia, which confers a risk of carcinoid tumor. A previous report demonstrated that pirenzepine, an M1 muscarinic receptor antagonist, enhances the acid inhibitory effects while suppressing hypergastrinemia induced by omeprazole. Here, we examined whether pirenzepine enhances the gastric acid inhibitory effects of vonoprazan without further increasing serum gastrin levels.Methods: Eleven healthy volunteers were subjected to 24-hour intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: pirenzepine 75mg alone, vonoprazan 10mg alone, and vonoprazan 10mg plus pirenzepine 75mg administered in a randomized crossover fashion.Results: Median pH 4 holding time ratios (range) achieved with pirenzepine 75mg, vonoprazan 10mg and vonoprazan 10mg plus pirenzepine 75mg were 6.9% (2.4–32.8%), 88.4% (54.6–100%), and 84.2% (40.3–100%), respectively. Respective serum gastrin levels were 79 (75–210) pg/ml, 310 (110–870) pg/ml, and 170 (140–930) pg/ml. In cases with hypergastrinemia (gastrin≥200pg/ml) induced by vonoprazan 10mg alone, concomitant treatment with pirenzepine significantly reduced serum gastrin levels from 370pg/ml to 180pg/ml (P=0.028).Conclusion: Although pirenzepine does not enhance acid inhibition, it does improve hypergastrinemia induced by vonoprazan to some extent.

Long-term acid suppression during vonoprazan therapy causes hypergastrinemia which may induce gastric mucosal changes such as fundic gland and hyperplastic polyps. The aim of this study is to clarify the long-term changes in serum gastrin levels and risk factors for hypergastrinemia.From July 2016 to April 2020, 48 patients receiving vonoprazan 10 mg once daily for more than one year were reviewed. Serum gastrin level was evaluated by radioimmunoassay in a fasting condition (reference range 37-172 pg/ml).The baseline median gastrin level was 100 (range, 54-415) pg/ml. The gastrin level over 4 years was 700-1200 pg/ml, which plateaued at 1.5 years. Multivariate analysis revealed factors associated with gastrin levels 12 months after starting vonoprazan and identified severe gastric atrophy as a significant positive risk factor (A continued increase in gastrin levels was not found during long-term vonoprazan therapy. Severe gastric atrophy is a significant risk factor for hypergastrinemia.

Studies on localization and distribution of enteroendocrine cells (EECs) are important for better understanding of their role in the ontogenetic development of intestines. Information about the distribution of the most important endocrine cells in the digestive tract of the ostrich is very limited; therefore, the aim of the present study was to identify gastrin and somatostatin EECs in the small intestine of the ostrich (Struthio camelus var. domesticus) chicks at different ages. Six embryos along with 42 ostriches of both sexes from hatching up to 60 days post-hatching, including six embryos, were obtained from an ostrich farm in Latvia. Duodenum, jejunum and ileum were investigated using routine histology and immunohistochemistry methods. Gastrin and somatostatin EECs were examined in 10 microscopic fields of the intestinal mucosa in each tissue sample. The cells were detected in all age groups as well as the embryos. The number of both types of EEC in the mucosa of the ileum was significantly lower (p

Von Hippel-Lindau (VHL) disease is a rare inherited familial syndrome complicated with various neoplasms, including neuroendocrine tumors (NETs). We herein report the first case of multiple gastric NETs in a 45-year-old man with VHL. He had multiple gastric polyps, and several endoscopic resected lesions were diagnosed as NETs. The serum gastrin level was elevated because he was taking a proton pump inhibitor (PPI). We suspected that gastrin had played a role in the development of NETs, and the remaining polyps were followed up with discontinuation of the PPI. The NETs gradually reduced in size until they became hard to notice on endoscopy and have remained nearly invisible for over eight years.

Objective: Proton pump inhibitor (PPI) drugs reduce gastric acid secretion and lead to an increase in serum gastrin levels. Many preclinical and some clinical researches have established some positive effects of gastrin or PPI therapy on glucose regulation. The aim of this study was to prospectively investigate the short term effects of esomeprazole on glycaemic control in patients with type 2 diabetes mellitus. In addition, the presence of an association between this effect and gastrin levels was evaluated. Methods: Thirty-two subjects with type 2 diabetes mellitus were enrolled and grouped as intervention (n=16) and control (n=16). The participants in the intervention group were prescribed 40 mg of esomeprazole treatment for three months. At the beginning of the study and at the 3rd month, HbA1c level (%) and gastrin levels (pmol/L) of participants were assessed. Then, the groups were compared in terms of their baseline and 3rd month values. Results: In the intervention group, the mean gastrin level increased significantly from 34.3±14.4 pmol/L to 87.4±43.6 pmol/L (p Conclusion: Our study demonstrates that esomeprazole has no extra benefit for the controlled diabetic patient in three months. However, in only the metformin-treated subgroup, esomeprazole may prevent the rise in HbA1c level.

Cholecystokinin (CCK) is a gut hormone which regulates gallbladder contraction and pancreatic enzyme secretion. In addition, CCK is also a major intestinal satiety signal. The knowledge about CCK in circulation, however, has been limited by difficulties in accurate measurement of the concentrations in plasma. Thus, CCK circulates in low concentrations and furthermore, it is structurally homologous to the antral hormone, gastrin, which circulates in higher concentrations. Therefore, most antibodies raised against CCK cross-react in immunoassays with gastrin. However, using highly sensitive and entirely specific in-house radioimmunoassays, which meet these challenges, we have now measured the daily concentration-variations of CCK and gastrin in plasma from young healthy men (

ObjectivesAutoimmune metaplastic atrophic gastritis (AMAG) is an underrecognized entity, especially in its early stage. This study assessed whether the use of gastrin immunohistochemistry would increase sensitivity for diagnosing early AMAG.MethodsThree-hundred gastric biopsies were prospectively stained for gastrin by immunohistochemistry. Inclusion criteria included well-oriented gastric mucosa with mucus glands and minimal plasma cell infiltrate not suspected to represent pyloric metaplasia. Patient age, sex, designated location of biopsy, presence or absence of intestinal metaplasia, and clinical information were not criteria. Any case with absence of gastrin-positive endocrine cells reflexed to chromogranin immunohistochemistry. Maloriented biopsies or cases with current Helicobacter infection were excluded.ResultsThe 298-patient study cohort comprised 222 females (mean age, 47 years; range, 16-80 years) and 76 males (mean age, 49 years; range, 7-80 years). Biopsies were designated as “antral/antral nodules” (61%), and the rest were labeled “gastric/random stomach” (39%). Nine cases (3%) exhibited absence of gastrin-positive endocrine cells; one of those showed endocrine cell hyperplasia by chromogranin staining.ConclusionsPathologists should be aware of the histologic features of early AMAG and meticulously analyze tissue regardless of specimen labeling. Gastrin immunostain is a supplemental diagnostic tool when encountering inflamed antral-appearing specimens.

Context The glycoprotein chromogranin A (CgA) is expressed by endocrine and neuroendocrine cells. High levels of serum CgA serve as markers of neuroendocrine tumors (NET), but its role in autoimmunity has not been assessed. Objective To investigate CgA utility as a marker of endocrine autoimmunity. Methods CgA serum levels were evaluated in 807 consecutive unselected participants (cross-sectional study) with the time-resolved amplified cryptate emission technology. Results Serum CgA concentrations were increased in 66%, 39%, 38%, and 24% of patients with NET, type 1 diabetes (T1D), autoimmune gastritis (AG) and autoimmune polyendocrinopathy (AP), respectively. Compared with healthy participant controls (C), the odds of positive CgA measurement were up to 28 times higher in the disease groups. In detail, the odds ratios (ORs) for positive CgA levels were 27.98, 15.22, 7.32 (all P Conclusion CgA qualifies as a novel biomarker for T1D, AP, and AG.

Goals The goal of this study was to elucidate the most important predictors for elevation of gastrin in patients on long-term PPI therapy through analysis of data from 2 published studies in Icelandic patients with erosive GERD. Background Gastrin elevation is a known but variable consequence of proton pump inhibitor (PPI) therapy. Concerns have been raised about the clinical importance of chronic PPI induced gastrin elevation. Study This cross-sectional analysis included patients with endoscopically verified erosive esophagitis receiving long-term PPI therapy. PPI exposure in dosage over weight (mg/kg) and dosage over body surface area (mg/m) was compared with fasting gastrin levels in two separate multiple linear regression models. Data was collected on age, gender, weight, H. pylori infection, smoking, PPI duration and type. Results Overall data from 157 patients (78 females) were analyzed. Median serum gastrin levels were higher in females than males (92 vs. 60 pg/mL; P=0.001). Simple linear regression showed a correlation between serum gastrin levels and gender (P=0.0008) as well as PPI exposure in mg/kg (P=0.0001) and mg/m (P=0.0001). Multiple linear regression analysis showed that PPI exposure, both in mg/kg (β=0.95 [CI=0.4-1.5]; P=0.001) and mg/m (β=0.02 [CI=0.0-0.0]; P=0.0015) along with female gender (β=0.2 [CI=0.0-0.4]; P=0.02) predicted higher gastrin values. Conclusions Dosage and female gender seem to play an important role in the development of gastrin elevation on PPI therapy. A significant correlation was found between fasting serum gastrin and dosage of PPIs over weight and body surface area.

Aim Develop a program to identify, treat, and prevent severe atrophic gastritis to reduce gastric cancer incidence and mortality. Materials and methods In total, 2,847 people aged > 40 years old underwent serological noninvasive screening for atrophic gastritis by identifying postprandial gastrin-17 and pepsinogen-1 in the fasting state. Anti-H pylori IgG was found in 2,134 patients. Seven years later, 2,220 patientswho had undergone serological noninvasive screening were asked to fill out a questionnaire survey (were interviewed). We could not find any information on 627 of 2,847 patients. Next, 75 patients with multifocal atrophic gastritis who underwent gastroscopy and biopsies (the Updated Sydney System (USS)) were selected. To study gastrin-17 production, morpho-functional correlation was studies in 75 patients with multifocal atrophic gastritis. Results During seven years, no reported case of gastric cancer was done among 2,220 persons who underwent serological screening and treatment. In the same population, 4.3 persons who did not receive screening during the same period, developed gastric cancer and died of it. In this study, we can say that 4.3 lives were saved out of 2,220 tested persons. The cost for screening this number of people amounted to €23,750. A comparison of the prevalence rate of the four stages of multifocal atrophic gastritis based on the data of the histopathology tests and noninvasive serologic screening in accordance with OLGA classification showed a strong correlation (the correlation coefficient is 0.812). This finding suggested that using this classification not only for histopathology tests for atrophic gastritis but also for serologic markers of antral mucosa and corpus ventriculi atrophy: gastrin-17 and pepsinogen-1. Conclusion Complex pathogenetic treatment of atrophic gastritis significantly reduced gastric cancer risk and incidence for such patients. .

Context Helicobacter pylori and Multiple Endocrine Neoplasia Type 1 (MEN 1) are risk factors for hypergastrinemia. Gastrin-secreting neoplasms of the foregut mucosa are both a source of, and potentially stimulated by, hypergastrinemia. Objective To determine the relationship between H pylori exposure and the prevalence and severity of hypergastrinemia in patients with MEN 1. Design, setting & patients Cross-sectional analysis of patients with a common MEN1 gene mutation managed at a tertiary referral hospital that underwent fasting serum gastrin and H pylori serum IgG measurement. Intervention H pylori IgG and serum gastrin concentration, determined via immunoassay. Main outcome measures The prevalence and severity of hypergastrinemia and its relationship to past H pylori exposure. Results Thirty-four of 95 (36%) patients were H pylori IgG seropositive. H pylori seropositive patients were significantly more likely to exhibit hypergastrinemia compared with seronegative patients (relative risk [RR] 1.72, P = .023). H pylori exposure also predicted severe hypergastrinemia (RR 3.52, P = .026 and RR 9.37, P = .031 for patients with gastrin ≥ ×4 and ≥ ×8 the upper limit of normal [ULN], respectively). Gastrin concentrations ≥ ×10 ULN occurred exclusively in H pylori seropositive patients (0/61 vs 6/34, P = .001). Serum gastrin and alpha subunit were positively associated in H pylori-exposed (β = 0.69, P = .001), but not in H pylori-unexposed patients. Conclusion Past H pylori exposure was associated with increased prevalence and severity of hypergastrinemia in MEN 1 patients. Past H pylori-related hypergastrinemia may contribute to the pathogenesis of ongoing gastrin hypersecretion by susceptible foregut neuroendocrine tissues.

The appropriate localization of gastrinoma is still difficult. We aimed to evaluate the diagnostic accuracy of selective arterial calcium injection (SACI) for localization of gastrinomas including multiple lesions. This retrospective study included ten patients with surgically proven gastrinomas (gastrinoma group) and six patients without any findings suggesting Zollinger-Ellison syndrome (non-gastrinoma group). For SACI, calcium gluconate was injected into the arteries supplying pancreas, duodenum, and liver. Blood samples from the hepatic vein were obtained before and 30, 60, and 120 seconds after each injection. The results were considered positive when the increase in serum immunoreactive gastrin (IRG) levels within 60 seconds of calcium gluconate injection were more than 80 pg/mL and more than 20% from baseline. We evaluated the efficacy of SACI by comparing the SACI responses with definitive locations diagnosed by clinical and histopathological findings. In the gastrinoma group, false-positive responses were confirmed in seven of the ten patients. False-negative response was observed in one of the feeding arteries of one patient with gastrinomas in multiple locations. Conversely, the greatest increase in serum gastrin levels from baseline at 30 seconds indicated the true-positive responses in all patients with gastrinomas. In the non-gastrinoma group, calcium gluconate injection into gastroduodenal artery evoked positive responses in five of the six patients. In conclusion, our data suggest the strongest gastrin response evoked by SACI indicates the definitive location in patients with gastrinomas. In contrast, SACI could not accurately locate multiple gastrin-secreting lesions due to poor specificity.

Background: Randomized and controlled trials of glucagon-like peptide-1 (GLP-1) derived drugs have shown that the most frequent adverse symptoms are gastrointestinal. Some of the side effects such as dyspepsia, nausea and upper abdominal pain may well be of gastric origin. Since the antral hormone gastrin regulates gastric secretion of acid and enzymes and contributes to the regulation of gastric motility, we examined the effect of GLP-1 on the secretion of gastrin in normal subjects and diabetes patients. Method: Plasma was sampled from ten healthy subjects and ten patients with diabetes mellitus type 1 with glucose clamped between 6 and 9 mM. GLP-1 or saline were infused for 4 h during and after a meal. Plasma concentrations of gastrin and GLP-1 were measured using specific radioimmunoassays. Results: Basal plasma concentrations of gastrin were similar in controls and patients. After the meal, the gastrin concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of gastrin significantly, most pronounced in the diabetes patients. Conclusions: The results show that GLP-1 infusion suppresses the postprandial secretion of gastrin in normal subjects and even more so in the diabetes patients. The results may therefore shed further light on the upper gastrointestinal side effects of GLP-1-derived drugs in diabetic patients.

BackgroundHypergastrinaemia occasionally indicates the presence of a gastrinoma. However it is much more commonly associated with various benign causes including proton pump inhibitor (PPI) use, Helicobacter pylori infection and/or atrophic gastritis. The extent to which these factors interact to influence fasting serum gastrin concentrations remains incompletely understood.Materials and MethodsFasting serum gastrin concentrations were measured by radioimmunoassay in 1,400 patients attending for diagnostic oesophagogastro-duodenoscopy. After exclusions, 982 patients were divided into four groups and their results analysed. We compared gastrin concentrations in normal patients (no H. pylori infection, no PPI use and no histological evidence of gastric preneoplasia (n=233)), with those in patients who were taking regular PPIs (H. pylori negative with no gastric preneoplasia (n=301)), patients who had active H. pylori infection but no gastric preneoplasia (n=164) and patients with histologically confirmed gastric preneoplasia (n=284).ResultsMedian fasting gastrin concentration in the normal group was 20pM and was significantly increased in PPI users (46pM, pH. pylori infection (27pM, pH. pylori (50pM, n=56) or who had antral gastric preneoplasia (53pM, n=87), but did not significantly alter serum gastrin concentrations in patients with corpus preneoplasia (90pM, n=66).ConclusionsPPI use, H. pylori infection and atrophic gastritis all caused significant elevations of median fasting gastrin concentrations. However, several patients who had potential risk factors for hypergastrinaemia still demonstrated fasting serum gastrin concentrations within the normal range.

Patients with multiple endocrine neoplasia 1 syndrome (MEN1) often develop multifocal duodenopancreatic neuroendocrine tumors (dpNETs). Nonfunctional pancreatic neuroendocrine tumors (PanNETs) and duodenal gastrinomas are the most frequent origins of metastasis. Current guidelines recommend surgery based on tumor functionality, size ≥ 2 cm, grade or presence of lymph node metastases. However, in case of multiple primary tumors it is often unknown which specific tumor metastasized. This study aims to unravel the relationship between primary dpNETs and metastases in patients with MEN1 by studying endocrine differentiation. First, it was shown that expression of the endocrine differentiation markers ARX and PDX1 was concordant in 18 unifocal sporadic neuroendocrine tumors (NETs) and matched metastases. Thereafter, ARX, PDX1, Ki67 and gastrin expression, and the presence of alternative lengthening of telomeres were determined in 137 microscopic and macroscopic dpNETs and 36 matched metastases in 10 patients with MEN1. ARX and PDX1 H-score clustering was performed to infer relatedness. For patients with multiple metastases, similar intrametastases transcription factor expression suggests that most metastases (29/32) originated from a single NET of origin, while few patients may have multiple metastatic primary NETs. In 6 patients with MEN1 and hypergastrinemia, periduodenopancreatic lymph node metastases expressed gastrin, and clustered with minute duodenal gastrinomas, not with larger PanNETs. PanNET metastases often clustered with high grade or alternative lengthening of telomeres-positive primary tumors. In conclusion, for patients with MEN1-related hypergastrinemia and PanNETs, a duodenal origin of periduodenopancreatic lymph node metastases should be considered, even when current conventional and functional imaging studies do not reveal duodenal tumors preoperatively.

Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanelAltogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing.Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κThe new generation GastroPanel

Acute myocardial infarction (MI) is one of the leading causes of death in humans. Our previous studies showed that gastrin alleviated acute myocardial ischaemia–reperfusion injury. We hypothesize that gastrin might protect against heart injury after MI by promoting angiogenesis. An MI model was simulated by ligating the anterior descending coronary artery in adult male C57BL/6J mice. Gastrin was administered twice daily by intraperitoneal injection for 2 weeks after MI. We found that gastrin reduced mortality, improved myocardial function with reduced infarct size and promoted angiogenesis. Gastrin increased HIF-1α and VEGF expression. Downregulation of HIF-1α expression by siRNA reduced the proliferation, migration and tube formation of human umbilical vein endothelial cells. These results indicate that gastrin restores cardiac function after MI by promoting angiogenesis via the HIF-1α/VEGF pathway.

Background It is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown. Methods Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 μg/Kg body weight/day, 100 μL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis. Results We found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCK2R) mediated the protective effect of gastrin since the CCK2R blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection. Conclusion Our data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate.

The clinical spectrum of autoimmune gastritis is silent in the early stages of the disease and no specific symptom is related to this entity. Although gastroscopic findings of this entity are well defined, data regarding colonoscopic findings are limited. The aims of this study were to determine the prevalence of colonoscopic findings and to explore factors that might affect these findings. This is a retrospective chart review of patients with autoimmune gastritis (n=240). Data regarding colonoscopic findings, serum gastrin and chromogranin A (CgA) levels and gastric histopathological results were extracted and compared with 550 patients positive for Helicobacter pylori and gastric atrophy. Control subjects had colonoscopy and gastroscopy with biopsies. Colorectal lesions were observed in 64 (26.6%) of patients with autoimmune gastritis and 36 (6.6%) patients had colorectal lesions in the control group (p

Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear.This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment.The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting.The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p 0.01).The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.

BACKGROUND Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterised by destruction of gastric oxyntic mucosa AIM: To explore gastric histopathological evolution in a cohort of AAG patients over a prolonged follow-up METHODS: Single centre prospective study enrolling consecutive patients with histologically confirmed AAG between 2000 and 2018. All AAG patients undergoing endoscopic follow-up every 1-3 years were classified as having stages 1, 2 or 3 according to atrophy severity (mild, moderate and severe). AAG patients with either glandular or neuroendocrine dysplasia/neoplasia were classified as having stage 4. Disease stage progression, and changes in serum anti-parietal cell antibody (PCA), chromogranin A and gastrin-17 were assessed. RESULTS In total, 282 AAG patients (mean age 60.3 years; F:M ratio 2.4:1; median follow-up 3 years, interquartile range 1-7) were enrolled. All patients with stages 1 or 2 progressed to stage 2 or 3 over time with a steady trend (P = .243) and regression from a severe to a milder stage was never noticed. Disease progression of patients with stages 1 or 2 occurred within the first 3 years. PCA positivity rate did not change over time. Stage 3 patients had higher gastrin-17 levels compared to patients with stages 1 and 2 (median 606 vs 295 pg/mL; P

Pancreatic cancer has been termed a 'recalcitrant cancer' due to its relative resistance to chemotherapy and immunotherapy. This resistance is thought to be due in part to the dense fibrotic tumor microenvironment and lack of tumor infiltrating CD8 + T cells. The gastrointestinal peptide, gastrin, has been shown to stimulate growth of pancreatic cancer by both a paracrine and autocrine mechanism. Interruption of gastrin at the CCK receptor may reduce tumor-associated fibrosis and alter tumor immune cells. Polyclonal Ab Stimulator (PAS) is a vaccine that targets gastrin and has been shown to prolong survival of patients with pancreatic cancer. Here, we report that PAS vaccination monotherapy elicits both a humoral and cellular immune response when used in immune competent mice-bearing pancreatic tumors and that PAS monotherapy produced a marked T-cell activation and influx of CD8 + lymphocytes into pancreatic tumors. Isolated peripheral lymphocytes elicited cytokine release upon re-stimulation with gastrin in vitro demonstrating specificity of immune activation for the target peptide. Combination therapy with PAS and PD-1 Ab activated CD4 -/CD8 - TEMRA cells important in T-cell-mediated tumor death and memory. Tumors of mice treated with PAS (250 μg) or PAS (100 and 250 μg) in combination with a PD-1 Ab were significantly smaller compared to tumors from PBS or PD-1 Ab-treated mice. When PAS was given in combination with PD-1 Ab, tumors had less fibrosis, fewer inhibitory Treg lymphocytes, and fewer tumor-associated macrophages. These findings reveal a novel approach to improve treatment strategies for pancreatic cancer.

Background The aim of our study was to assess clinico-pathological and biochemical parameters of Type 1 Gastric Neuroendocrine Neoplasms (GNEN1) with respect to tumours propensity for recurrence and metastasis. Methods Hospital charts of GNEN1 patients were reviewed at a single tertiary referral centre. Results We included 114 consecutive patients (74 women; age at baseline 54.5 ± 12.7 years [mean ± SD]) with GNEN1. All tumours (n = 114) were well differentiated; Grade 1 (G1) accounted for 56 patients (49%), whereas 46 (40%) were Grade 2 (G2) and 12 (11%) of unknown Grade. Overall follow-up encompassed 45.3 ± 46 (mean ± SD) months in 84 patients who were subjected to annual surveillance; 44 (52%) developed recurrence in the stomach during follow-up with 22 experiencing multiple recurrences; three (2.6%) presented with metastases in locoregional lymph nodes (n = 3) and/or the liver (n = 2); No metastasis or death was reported during follow-up. Median recurrence-free survival (RFS) was 31 months (95% CI: 7.6-54.4). Among clinico-pathological and biochemical parameters investigated, endoscopic intervention compared with surgery (P-value = .009) and higher serum-gastrin levels (s-gastrin) at baseline and first-year follow-up were associated with recurrence (P-value = .022 and .003 respectively) and also shorter RFS (log-rank P = .009 for type of intervention and .014 for s-gastrin, respectively). Receiver Operator Curve analysis of s-gastrin levels at first-year follow-up for recurrence demonstrated an area under the curve of 0.702. Conclusion Despite the relatively high prevalence of G2 tumours, endoscopically and/or surgically treated GNEN1 remains an indolent disease with a low metastatic propensity and no disease-specific mortality reported in our series. Many patients though will experience local recurrence, warranting long-term endoscopic surveillance with s-gastrin biomarker being a complementary tool in recurrence prediction.

To investigate the efficacy of long-term (52 weeks) maintenance therapy by 10-mg vonoprazan administration for proton pump inhibitor-resistant reflux esophagitis continued from the preceding study. Sixteen patients with proton pump inhibitor-resistant reflux esophagitis (mean age 70.9 years, eight males) in whom endoscopic healing was achieved by 20-mg vonoprazan administration for 4 weeks and maintenance of remission was maintained by 10-mg vonoprazan administration for 8 weeks were enrolled. Endoscopy was performed at 52 weeks after the initiation of maintenance therapy with 10-mg vonoprazan to evaluate whether there was any recurrence of reflux esophagitis. Changes in the gastric mucosa were investigated at 52 weeks. Symptoms were assessed using the frequency scale for the symptoms of gastroesophageal reflux disease and the fast gastrin level at 8 and 52 weeks following the maintenance therapy. Endoscopic remission was maintained at 52 weeks in 15 (93.8%) of the 16 patients with proton pump inhibitor-resistant reflux esophagitis. One patient relapsed with grade C of reflux esophagitis. There were no significant differences in the symptom score at 8 and 52 weeks, nor the gastrin level at 8 and 52 weeks. There was no change in the stomach on endoscopy at 52 weeks. Long-term maintenance therapy by 10-mg vonoprazan administration is very effective for proton pump inhibitor-resistant reflux esophagitis patients in whom endoscopic healing was maintained by 8 weeks maintenance therapy with 10-mg vonoprazan administration.

Aim To determine if a 4-week course of 14 mg weekly GLP-1 agonist LY2428757 combined with 3 mg or 2 mg daily gastrin analogue TT223 (LY+TT223) results in long-term glycaemic changes. Materials and methods Patients with in adequately-controlled type 2 diabetes mellitus ±metformin (N=151) were randomized to a 4-week course of LY+TT223 (3 mg), LY+TT223 (2 mg), LY+TT223 placebo (LY-only) or LY placebo+TT223 placebo (placebo). The primary objective was change in HbA1c from baseline to 5 month safter completion of therapy (i.e. at 6 months) and safety and tolerability with LY+TT223 versus LY-only. Results LY groups showed HbA1c reductions during the active treatment phase. These did not persist during follow-up phase. Combining TT223 with LY did not result in additional glycaemic effects during treatment or follow-up. At 6 months, LSM ± SE for change in HbA1c from baseline was: LY+TT223 (3 mg): -0.1 ± 0.2%; LY+TT223 (2 mg): 0.1 ± 0.2%; LY-only: -0.2 ± 0.2%; placebo: 0.04 ± 0.2%. Secondary analyses were consistent with primary results. LY+TT223 was not superior to LY for other time points or end points, including insulin secretory response to mixed meal tolerance tests. The most common adverse events (nausea and vomiting) were more frequent with LY+TT223 versus LY-only. The safety profile was consistent with previous findings. Conclusion GLP-1+gastrin combination therapy did not improve glycaemic control versus GLP-1 alone.

Purpose: Peptide receptor radionuclide therapy (PRRT) with the radiolabeled somatostatin analogue [Lutetium-177-DOTA0 -Tyr3 ]octreotate (177Lu-DOTATATE) is widely applied for inoperable metastatic small intestinal and nonfunctioning pancreatic neuroendocrine tumors (pNETs). The aim of this study is to describe the safety and efficacy of the treatment of functioning pNETs. Methods: Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gbq per cycle. Radiological (Response Evaluation Criteria in Solid Tumors 1.1), symptomatic, and biochemical response were analyzed retrospectively for all patients with a functioning pNET (insulinoma, gastrinoma, VIPoma, and glucagonoma) treated with 177Lu-DOTATATE. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core Module questionnaire. Results: Thirty-four patients with a metastatic functioning pNET (European Neuroendocrine Tumor Society grade 1 or 2) were included: 14 insulinomas, 5 VIPomas, 7 gastrinomas, and 8 glucagonomas. Subacute hematological toxicity, grade 3 or 4 occurred in 4 patients (12%) and a hormonal crisis in 3 patients (9%). PRRT resulted in partial or complete response in 59% of patients and the disease control rate was 78% in patients with baseline progression. 71% of patients with uncontrolled symptoms had a reduction of symptoms and a more than 80% decrease of circulating hormone levels was measured during follow-up. After PRRT, median progression-free survival was 18.1 months (interquartile range: 3.3 to 35.7) with a concurrent increase in QOL. Conclusion: Treatment with 177Lu-DOTATATE is a safe and effective therapy resulting in radiological, symptomatic and biochemical response in a high percentage of patients with metastatic functioning pNETs. Hormonal crises occur relatively frequent and preventive therapy should be considered before and/or during PRRT

To evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for non-erosive reflux disease. On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 8 weeks by 30 patients (11 men, mean age: 67.8) with non-erosive reflux disease who responded well to maintenance therapy using proton pump inhibitor and answered “very satisfied” or “satisfied” to an overall satisfaction survey (5-grade scale). The degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin levels before breakfast was examined before and after on-demand therapy. The number of vonoprazan tablets taken and the frequency (regular, temporary, rare) of its administration were also investigated. All patients completed 8-week on-demand therapy with 20-mg vonoprazan. Comparisons of patient satisfaction levels before and after therapy revealed no significant differences in the number of patients who were very satisfied and satisfied with the therapy. Furthermore, there were no significant differences in score of symptoms or gastrin levels before and after therapy. During 8-week on-demand therapy, patients took 11 tablets (median) (7.0–18.0 tablets: 25–75 percentiles), and 30.0% of patients (n = 9) took vonoprazan on a regular basis (at least 2 tablets a week). On-demand therapy with 20-mg vonoprazan exerted equivalent effects to continuous PPI maintenance therapy for patients with non-erosive reflux disease.

Postoperative ileus (POI) is a common complication after abdominal surgery. Invasive stimulation of the cervical vagus nerve is known to reduce inflammatory response and ameliorated POI after surgery in a mouse model. However, the transcutaneous vagus nerve stimulation (tVNS) is a possible non-invasive approach. In this clinical study, we aimed to investigate the effect of tVNS on the activation of the stomach muscle in humans. Patients requiring open laparotomy were screened for this prospective proof of concept clinical study. After open laparotomy, muscle activity of the stomach was measured by a free running electromyography (EMG) before and during tVNS on the ear. Frequency and amplitude of compound gastric action potentials were the electrophysiological parameters we assessed to reveal the changes in electro motor gastric activity. Gastrin levels as a surrogate marker for vagus nerve activation was analyzed before, 1 and 3 h after tVNS. Fourteen patients were included, no severe adverse events and no medical device related adverse events occurred. tVNS led to significant reduction of action potential frequency and significant elevation of action potential amplitude in the stomach compared to control. Gastrin levels were significantly elevated 3 h after tVNS compared to levels before tVNS. Application of tVNS is a safe and feasible procedure during surgical intervention. Our results provide evidence that tVNS activates efferent visceral vagal fibers. Therefore, this low risk and easy to perform method could be useful to prevent postoperative ileus. DRKS00013340.

Highlights • A peptidomic analysis of the human and mouse gastrointestinal tract was performed. • High fat feeding reduced the content of GCG, PYY and INSL5 in the distal colon. • Several interesting novel peptides were synthesised for in vivo characterisation. • A novel product of progastrin modestly improved glucose tolerance in lean mice., Objectives To analyse the peptidomics of mouse enteroendocrine cells (EECs) and human gastrointestinal (GI) tissue and identify novel gut derived peptides. Methods High resolution nano-flow liquid chromatography mass spectrometry (LC–MS/MS) was performed on (i) flow-cytometry purified NeuroD1 positive cells from mouse and homogenised human intestinal biopsies, (ii) supernatants from primary murine intestinal cultures, (iii) intestinal homogenates from mice fed high fat diet. Candidate bioactive peptides were selected on the basis of species conservation, high expression/biosynthesis in EECs and evidence of regulated secretionin vitro. Candidate novel gut-derived peptides were chronically administered to mice to assess effects on food intake and glucose tolerance. Results A large number of peptide fragments were identified from human and mouse, including known full-length gut hormones and enzymatic degradation products. EEC-specific peptides were largely from vesicular proteins, particularly prohormones, granins and processing enzymes, of which several exhibited regulated secretion in vitro. No regulated peptides were identified from previously unknown genes. High fat feeding particularly affected the distal colon, resulting in reduced peptide levels from GCG, PYY and INSL5. Of the two candidate novel peptides tested in vivo, a peptide from Chromogranin A (ChgA 435−462a) had no measurable effect, but a progastrin-derived peptide (Gast p59−79), modestly improved glucose tolerance in lean mice. Conclusion LC–MS/MS peptidomic analysis of murine EECs and human GI tissue identified the spectrum of peptides produced by EECs, including a potential novel gut hormone, Gast p59−79, with minor effects on glucose tolerance.

Background and Aims: In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms. Methods: We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD. Results: At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett’s esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p

Hypergastrinemia has been associated with high grade dysplasia and adenocarcinoma in patients with Barrett’s esophagus (BE), and experimental studies suggest pro-inflammatory and pro-neoplastic effects of gastrin on BE. This is of potential concern, as BE patients are treated with medications that suppress gastric acid production, resulting in increased physiologic levels of gastrin. We aimed to determine whether treatment with the novel gastrin/CCK(2) receptor antagonist netazepide reduces expression of markers associated with inflammation and neoplasia in BE. This was a randomized, double-blind, placebo-controlled trial of netazepide in patients with BE without dysplasia. Subjects were treated for 12 weeks, with endoscopic assessment at baseline and at end of treatment. The primary outcome was within-individual change in cellular proliferation as assessed by Ki67. Secondary analyses included changes in gene expression, assessed by RNA-sequencing, and safety and tolerability. A total of 20 subjects completed the study and were included in the analyses. There was no difference between arms in mean change in cellular proliferation (netazepide: +35.6 Ki67+ cells/ mm(2), SD 620.7; placebo: +307.8 Ki67+ cells/ mm(2), SD 640.3; p=0.35). Netazepide treatment resulted in increased expression of genes related to gastric phenotype (TFF2, MUC5B) and certain cancer-associated markers (REG3A, PAX9, MUC1), and decreased expression of intestinal markers MUC2, FABP1, FABP2, and CDX1. No serious adverse events related to study drug occurred. The gastrin/CCK(2) receptor antagonist netazepide did not reduce cellular proliferation in patients with non-dysplastic BE. Further research should focus on the biological effects of gastrin in Barrett’s esophagus.

Background and Aims: Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG. Methods: Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared. Results: Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit. Conclusions: Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated.

In order to explore the changes of intestinal flora and serum levels of relevant substances in patients with gastric cancer before and after surgery with carbon nanoparticle laparoscopy, a total of 180 patients with early distal gastric cancer who adopted laparoscopic radical gastrectomy for distal gastric cancer in the general surgery department of TCM Hospital of Shi Jia Zhuang City from January 2018 to January 2020 were selected and randomly divided into two groups: traditional laparoscopic operation (control group) and carbon nanoparticle laparoscopic operation (experimental group) were adopted for treatment for the two groups, respectively. Postoperative evaluation included the difference between the two groups in the operative time, the efficiency of intraoperative lymph node dissection, and the number of lymph node detection. The adverse reactions, changes of intestinal flora before and after surgery in the two groups, and the serum levels of epidermal growth factor receptor (EGFR), interleukin-32 (IL-32), and gastrin 17 were evaluated. In the experimental group, the success rate of carbon nanoparticle tracer black staining reached 100%, and the operation time of the experimental group was significantly shorter than that of the control group ( P < 0.05 ). The lymph node detection rate of the experimental group was higher than that of the control group ( P < 0.05 ), but there was no significant difference in the lymph node metastasis rate between the two groups ( P > 0.05 ). The sentinel lymph node sensitivity of the experimental group reached 92.3%, and the specificity, accuracy, and positive and negative prediction rates reached 100%; the experimental group patients were with an obviously higher incidence of level I-II gastrointestinal reaction ( P < 0.05 ). Postoperative increases in Bifidobacteria and Lactobacillus were observed in both groups, while decreases in Enterococcus and Escherichia coli were observed in both groups ( P < 0.05 ). Moreover, the degree of increase and decrease in the experimental group was greater than that in the control group ( P < 0.05 ). The serum levels of EGFR, IL-32, and gastrin 17 in the two groups were significantly lower than those in the control group on 3 d, 7 d, and 15 d after surgery ( P < 0.05 ). In the radical gastrectomy for distal gastric cancer, carbon nanoparticle laparoscopy was not only helpful for the localization of small tumors but also for the thorough dissection of lymph nodes after the surgery, and the postoperative adverse reactions of carbon nanoparticle laparoscopy were also less, which was of great significance for the improvement of intestinal flora and the reduction of serum levels of EGFR, IL-32, and gastrin 17 in gastric cancer patients.

Gastrin elevation secondary to proton pump inhibitor (PPI) therapy is well documented. Recent studies have demonstrated a sex-related difference where females on PPIs have significantly higher baseline gastrin levels than males. The aim of the study was to analyse the pharmacokinetics of esomeprazole and short-term effect on serum gastrin levels and evaluate potential sex-related difference. Healthy volunteers received 40 mg of esomeprazole daily for five days. After the 1st and 5th dose blood samples for fasting gastrin and pharmacokinetic analysis were collected at scheduled time-points for eight hours. Esomeprazole was analysed by liquid chromatography and gastrin concentrations were measured using radioimmunoassay. A total of 30 volunteers were enrolled. Females had higher median baseline gastrin (pM) than males 12 (IQR 10–15) vs. 7 (IQR 4–11) (p = .03). In the study cohort, median gastrin levels rose from 10 (IQR 6–14) to 15 (IQR 13–20) (p = .0002). The serum levels for esomeprazole increased by an average of 299.8 ng/mL (p p = .15). In healthy volunteers, serum gastrin increased significantly after a four-day PPI-therapy. There was also a significant increase in serum esomeprazole from day 1 to day 5. The increase in gastrin and esomeprazole concentration was not related to sex and no significant sex-related difference was found in terms of pharmacokinetic parameters. European Clinical Trial Database (2015-002230-41).

IntroductionIn the UK, the fasting plasma concentrations of a panel of gut hormones (comprising vasoactive intestinal peptide (VIP), gastrin, pancreatic polypeptide (PP), glucagon, somatostatin and chromogranin A) are measured to evaluate patients who have or who (due to unexplained and compatible symptoms) are suspected of having neuroendocrine tumors (NETs). False positive elevated hormone concentrations are sometimes found.ObjectiveTo evaluate the frequency and implications of false positive fasting gut hormone results.MethodsRetrospective audit of fasting gut hormone profile results at a large UK university teaching hospital over 12 months.ResultsFasting gut hormone concentrations were measured in 231 patients during 2017. No NETs were found in the 88 patients who had this test performed only to investigate symptoms. 31 false positive gastrin, 8 false positive chromogranin A, two false positive glucagon, three false positive somatostatin, one false positive PP, and one false positive VIP results were found. We extended the audit for glucagon and somatostatin for an additional two years and found seven probable false-positive raised glucagon concentrations and four probable false-positive elevated plasma somatostatin concentrations in total.ConclusionsFalse-positive elevations of plasma gastrin and chromogranin A were common and causes such as proton pump inhibitor use or inadequate fasting accounted for most cases. Elevated plasma concentrations of the other gut hormones were also detected in patients who had no other evidence of NET. Other diagnoses (e.g. cirrhosis and medullary thyroid carcinoma for hypersomatostatinemia and type 2 diabetes mellitus, pancreatitis, liver or renal impairment for hyperglucagonemia) may cause these false positive results.

To investigate the effect of Poria and effective constituents on gastrointestinal injury animals in the area of the side effects which caused by Rhubarb. Mice were administered i.g. with Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with high, medium and low doses of poria water extract and it's subfractions for 5 days. All indexes were determined to evaluate the action of poria in the pair treatment. The results showed that the higher dose of poria water decoction was discovered to be the most effective dose to treat gastrointestinal injury induced by rhubarb. Body weight, thymus and spleen indexes, the small intestinal propulsion rate and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference with the model group (P0.01). EAF (Ethyl Acetate Fraction), PEF (Petroleum Ether Fraction) and CPF (Crude Polysaccharide Fraction) not only increase the levels of AMS, GAS and VIP significantly but also ameliorate diarrhea and intestinal injury situation compared with the model group (P0.01). EAF, PEF and CPF were the most effective components to alleviate diarrhea and gastrointestinal injury induced by rhubarb.

We herein report a case of gastric hyperplastic polyps after argon plasma coagulation (APC) for gastric antral vascular ectasia (GAVE) in the antrum of a 65-year-old man with liver cirrhosis and hypergastrinemia induced by long-term proton pump inhibitor (PPI) use. Two years after APC therapy, endoscopy demonstrated multiple gastric polyps in the antrum and angle. A gastric polyp biopsy indicated foveolar epithelium hyperplasia, which was diagnosed as gastric hyperplastic polyps. One year after switching to an H2 blocker antagonist, endoscopy revealed that the polyps and GAVE had disappeared, with normal gastrin levels suggesting that PPI-induced hypergastrinemia had caused gastric hyperplastic polyps after APC therapy, and the polyps had disappeared after discontinuing PPIs.

Huntingtin-associated protein 1 (HAP1) is a neuronal cytoplasmic protein that is predominantly expressed in the brain and spinal cord. In addition to the central nervous system, HAP1 is also expressed in the peripheral organs including endocrine system. Different types of enteroendocrine cells (EEC) are present in the digestive organs. To date, the characterization of HAP1-immunoreactive (ir) cells remains unreported there. In the present study, the expression of HAP1 in pyloric stomach in adult male rats and its relationships with different chemical markers for EEC [gastrin, marker of gastrin (G) cells; somatostatin, marker of delta (D) cells; 5-HT, marker of enterochromaffin (EC) cells; histamine, marker of enterochromaffin-like (ECL) cells] were examined employing single- or double-labelled immunohistochemistry and with light-, fluorescence- or electron-microscopy. HAP1-ir cells were abundantly expressed in the glandular mucosa but were very few or none in the surface epithelium. Double-labelled immunofluorescence staining for HAP1 and markers for EECs showed that almost all the G-cells expressed HAP1. In contrast, HAP1 was completely lacking in D-cells, EC-cells or ECL-cells. Our current study is the first to clarify that HAP1 is selectively expressed in G-cells in rat pyloric stomach, which probably reflects HAP1's involvement in regulation of the secretion of gastrin.

Background Gastrin‐17 (G‐17) and Helicobacter pylori (H pylori) antibody are widely used in the screening of gastric diseases, especially in gastric cancer. In this study, we aimed to evaluate the value of G‐17 and H pylori antibody in gastric disease screening. Methods Healthy males and females (1368 and 1212, respectively) aged between 21‐80 years were recruited for the study. Serum G‐17 value was measured using ELISA, and H pylori antibodies were measured using Western blotting. Statistical analyses were performed using the chi‐square, Mann‐Whitney U, and Kruskal‐Wallis H tests. Results Serum G‐17 level was higher in the H pylori‐positive group than in the negative group. Serum G‐17 level was higher in the type 1 H pylori‐positive group than in the type 2 H pylori‐positive group. Further, serum G‐17 level was higher in females than in males and showed significant differences among different age‐groups, with changes in trend proportional to the age. The positive rate of H pylori infection in all the subjects was 58.29% and did not show a significant difference between males and females. However, it showed significant differences among different age‐groups, with the changing trend proportional to the age. Conclusion Analysis of serum G‐17 level and H pylori antibody typing is valuable in gastric disease screening. Every laboratory should establish its own reference interval for G‐17 level., Serum G‐17 level was higher in females than in males, and the changing trend of serum G‐17 level was proportional to age.

Human studies have demonstrated that physiologically relevant changes in circulating glucagon‐like peptide‐1 (GLP‐1) elicit a rapid increase in renal sodium excretion when combined with expansion of the extracellular fluid volume. Other studies support the involvement of various gastrointestinal hormones, e.g., gastrin and cholecystokinin (CCK) in a gut‐kidney axis, responsible for a rapid‐acting feed‐forward natriuretic mechanism. This study was designed to investigate the hypothesis that the postprandial GLP‐1 plasma concentration is sensitive to the sodium content in the meal. Under fixed sodium intake for 4 days prior to each experimental day, 10 lean healthy male participants were examined twice in random order after a 12‐hr fasting period. Arterial blood samples were collected at 10–20‐min intervals for 140 min after 75 grams of oral glucose + 6 grams of oral sodium chloride (NaCl) load versus 75 grams of glucose alone. Twenty‐four‐hour baseline urinary sodium excretions were similar between study days. Arterial GLP‐1 levels increased during both oral glucose loads and were significantly higher at the 40–80 min period during glucose + NaCl compared to glucose alone. The postprandial arterial responses of CCK, gastrin, and glucose‐dependent insulinotropic polypeptide as well as glucose, insulin, and C‐peptide did not differ between the two study days. Arterial renin, aldosterone, and natriuretic peptides levels did not change within subjects or between study days. Angiotensin II levels were significantly lower at the time GLP‐1 was higher (60–80 min) during glucose + NaCl. Sodium intake in addition to a glucose load selectively amplifies the postprandial GLP‐1 plasma concentration. Thus, GLP‐1 may be part of an acute feed‐forward mechanism for natriuresis., This study demonstrates that postprandial glucose‐driven glucagon‐like peptide‐1 (GLP‐1) secretion is sensitive to dietary sodium chloride intake and that this is associated with significantly lower angiotensin II (ANG II) but not aldosterone concentrations. In perspective, this feed‐forward Na+‐driven GLP‐1/ANGII response could have an impact on renal Na+‐handling.

Radiolabeled gastrin analogues have been proposed for theranostics of cholecystokinin subtype 2 receptor (CCK(2)R)-positive cancer. Peptide radioligands based on other receptor antagonists have displayed superior pharmacokinetics and higher biosafety than agonists. Here, we present DGA1, a derivative of the nonpeptidic CCK(2)R antagonist Z-360 carrying an acyclic tetraamine, for [(99m)Tc]Tc labeling. Preclinical comparison of [(99m)Tc]Tc-DGA1 with [(99m)Tc]Tc-DG2 (CCK(2)R-agonist reference) was conducted in HEK293-CCK(2)R/CCK(2i4sv)R cells and mice models, qualifying [(99m)Tc]Tc-DGA1 for further study in patients with CCK(2)R-positive tumors and single-photon emission computed tomography/CT.

Background Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children. Materials and methods We evaluated the presence of AIG and H pylori infection in fifty-three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded. Results The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min-max: 5.2-18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non-AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin-like cell hyperplasia. Conclusions Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia.

Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 × 109 CFU or 5 × 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.

Proton pump inhibitors (PPIs) are administered commonly to aged people, however, their effect on colorectal cancer (CRC) has still not been fully elucidated. Here, we examined the effect of PPIs and consequent alkalization on CRC cells. PPI administration alkalized the fecal pH and increased serum gastrin concentration. PPI and pH8 treatment (alkalization) of CMT93 mouse colon cancer cells inhibited cell growth and invasion, increased oxidative stress and apoptosis, and decreased mitochondrial volume and protein levels of cyclin D1 and phosphorylated extracellular signal-regulated kinase (pERK) 1/2. In contrast, gastrin treatment enhanced growth and invasion, decreased oxidative stress and apoptosis, and increased mitochondrial volume and cyclin D1 and pERK1/2 levels. Concurrent treatment with a PPI, pH8, and gastrin increased aldehyde dehydrogenase activity and also enhanced liver metastasis in the BALB/c strain of mice. PPI administration was associated with Clostridium perfringens enterotoxin (CPE) in CRC lesions. CPE treatment activated yes-associated protein (YAP) signals to enhance proliferation and stemness. The orthotopic colon cancer model of CMT93 cells with long-term PPI administration showed enhanced tumor growth and liver metastasis due to gastrin and YAP activation, as indicated by gastrin receptor knockdown and treatment with a YAP inhibitor. These findings suggest that PPI promotes CRC growth and metastasis by increasing gastrin concentration and YAP activation, resulting in gut flora alteration and fecal alkalization. These findings suggest that PPI use in colorectal cancer patients might create a risk of cancer promotion.

Objective Diagnosing gastric cancer (GC) at early stages is important for reducing its mortality. This study evaluated the diagnostic value of serum pepsinogen (PG) I, PGII, and gastrin-17 (G17) levels in screening for early-stage GC. Methods Serum levels of PGI, PGII, and G17 were measured in patients with upper digestive tract symptoms or GC family histories, and the PGI to PGII ratio (PGR) was calculated. Receiver operator characteristic curves were used to determine the thresholds of PGI, PGR, and G17 for GC diagnosis. Results Among the 949 patients examined by gastroscopy, 13 (1.37%) had GC, including five cases of early-stage GC and eight cases of progressive GC. PGI, PGR, and G17 showed good specificity and sensitivity for early-stage and progressive GC. The optimal thresholds of PGI, G17, and PGR were 71.85 μg/L, 15.65 pmol/L and 5.04 for the diagnosis of early-stage GC, respectively, and were 42.55 μg/L, 20.55 pmol/L, and 2.79 for the diagnosis of progressive GC, respectively. Conclusion Combining PG and G17 serum levels with gastroscopy could be a promising approach to screen for early-stage GC.

A hospital-based cross-sectional study in SIGES project was conducted during 2016.5–2017.5 in West China Hospital. It was aimed to observe the prevalence of atrophic gastritis (AG) in southwest China, and assess the diagnostic strength of serum gastrin-17 (G-17) in predicting AG in Chinese population. Asymptomatic healthy controls from health check-up, cancer-free patients with unspecific upper gastrointestinal symptoms, and histologically proven gastric cancer patients were eligible, if serum pepsinogen-I (PG-I), PG-II, and G-17 were detected. AG status was classified by the accredited cutoffs of PG-I (30 pmol/L, aOR = 314.41, 95% CI 166.10–595.12). Throughout the progression of stomach diseases, the diagnostic strength of serum G-17 for AG showed a downhill trend across more advanced situations. In despite of that, serum G-17 displayed a good performance in predicting AG in the entire cross-sectional population (AUC = 0.92, 95% CI 0.89–0.94; SEN = 85.5%; SPE = 93.2%; LR+ = 12.55; LR− = 0.11). Population in southwest China had intermediate prevalence of AG, while the prevalence was increased over age or disease progression. High level of serum G-17 might be a reliable non-invasive measurement to predict AG in southwest Chinese population.

Gastrin and cholecystokinin (CCK) are hormones released from endocrine cells in the antral stomach (gastrin), the duodenum, and the jejunum (CCK). Recent reports, based on secretion experiments in an enteroendocrine cell line (NCI‐H716) and gastrin receptor expression in proglucagon‐expressing cells from the rat colon, suggested that gastrin could be a regulator of glucagon‐like peptide‐1 (GLP‐1) secretion. To investigate these findings, we studied the acute effects of CCK‐8 (a CCK1/CCK2 (gastrin) receptor agonist) and gastrin‐17 (a CCK2(gastrin) receptor agonist) in robust ex vivo models: the isolated perfused rat small intestine and the isolated perfused rat colon. Small intestines from Wistar rats (n = 6), were perfused intraarterially over 80 min. During the perfusion, CCK (1 nmol/L) and gastrin (1 nmol/L) were infused over 10‐min periods separated by washout/baseline periods. Colons from Wistar rats (n = 6) were perfused intraarterially over 100 min. During the perfusion, CCK (1 nmol/L), vasoactive intestinal peptide (VIP) (10 nmol/L), and glucose‐dependent insulinotropic polypeptide (GIP) (1 nmol/L) were infused over 10‐min periods separated by washout/baseline periods. In the perfused rat small intestines neither CCK nor gastrin stimulated the release of GLP‐1 or neurotensin. In the perfused rat colon, neither CCK or VIP stimulated GLP‐1 or peptide YY (PYY) release, but GIP stimulated both GLP‐1 and PYY release. In both sets of experiments, bombesin, a gastrin‐releasing peptide analog, served as a positive control. Our findings do not support the suggestion that gastrin or CCK participate in the acute regulation of intestinal GLP‐1 secretion, but that GIP may play a role in the regulation of hormone secretion from the colon., Recent reports, based on secretion experiments in an enteroendocrine cell line (NCI‐H716) and gastrin receptor expression in proglucagon‐expressing cells from the rat colon, suggested that gastrin could be a regulator of glucagon‐like peptide‐1 (GLP‐1) secretion. To investigate these findings, we studied the acute effects of CCK‐8 (a CCK1/CCK2 (gastrin) receptor agonist) and gastrin‐17 (a CCK2(gastrin) receptor agonist) in the isolated perfused rat small intestine and the isolated perfused rat colon. Our findings do not support the suggestion that gastrin or CCK participate in the acute regulation of intestinal GLP‐1 secretion, but that GIP, unexpectedly, may play a role in the regulation of hormone secretion from the colon.

International audience; Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. Material and Methods: In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. Results: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P =.015] and corpus AG [61.0% (95% CI 49.2; 72.0), P =.004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P =.068). Conclusion: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.