Serum Gastrin Concentrations Research Articles

Evaluation of Two Commercial ELISA Kits for Measuring Equine Serum Gastrin Compared to Radioimmunoassay.

Gastrin is an important hormone involved in gastric acid secretion. Despite its importance, validated methods other than radioimmunoassay (RIA) to assess serum gastrin concentrations in horses are lacking. This study aims to determine the agreement between ELISA and RIA in quantifying equine serum gastrin concentrations. Serum gastrin concentrations were quantified using two ELISA kits and RIA. Samples (196) from 14 horses at different time points were analyzed using one ELISA kit and RIA, selected samples (7) were analyzed using a second ELISA kit, and the correlation between methods was calculated. The level of agreement was analyzed by Bland-Altman analysis and differences between ELISA and RIA were plotted against averages for each sample. The Pearson correlation between gastrin concentrations measured by ELISA and the RIA was 0.27 and -0.32 for ELISA kit 1 and kit 2, respectively. Mean bias (ELISA-RIA) was 198.40 pg/mL (95% CI: -142.95-539.76) and -17.90 pg/mL (95% CI: -89.98-54.19) for ELISA kit 1 and kit 2, respectively. Measurements of horse gastrin by both ELISA methods were highly variable, with an unacceptable correlation to the reference method, RIA. Using non-validated ELISA methods to quantify horse gastrin cannot be recommended.

Oriented immobilization of antibodies through peptide ligands for ultrasensitive detection of gastrin 17 in human serum via lateral flow immunoassay

Gastrin 17 (G-17) is a major biomarker for the diagnosis of gastric cancer. As the serum concentrations of gastrin are low, highly sensitive detection methods are needed. Previous studies have shown that oriented immobilization of detection antibodies can improve the sensitivity of lateral flow immunoassay (LFIA) methods. Herein, the antibody binding capacity of four Fc-specific peptides reported in different studies was evaluated, and two peptides with better binding potency were further modified with cysteine or the peptide GAC at their C-terminus. The peptide FYWHCLDEGAC exhibited the highest antibody binding capacity and was applied to directly immobilize the anti-G-17 antibody on microspheres with carboxyl-functionalized surfaces and europium-based time-resolved fluorescence. An LFIA method was developed to detect G-17 in human serum, and the limit of detection (LOD) of this method for G-17 was 0.08 pmol L-1, which was 10 times less than that of the nonoriented immobilization method. The working range of this method is 0.27 ∼ 600 pmol L-1, with a recovery rate of 85.2 % −106.7 % and a CV value less than 12.4 %. This method is easy to use, and the total detection process takes less than 20 min. The test results for the actual serum samples were consistent with the commercial kit results (R2 > 0.95), demonstrating that the method can be utilized for point-of-care testing of G-17. This approach to orientedly immobilize antibodies on nanomaterials can be used to develop sensitive LFIA methods for various molecules.

Beneficial Effect of Heat-Killed Lactic Acid Bacterium Lactobacillus johnsonii No. 1088 on Temporal Gastroesophageal Reflux-Related Symptoms in Healthy Volunteers: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study.

A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, Lactobacillus johnsonii No. 1088 (LJ88) on temporal gastroesophageal reflux-related symptoms in healthy volunteers. A total of 120 healthy Japanese volunteers of both sexes, aged between 21 and 63 years, whose Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) total score was 8 or greater, but who were not diagnosed with functional dyspepsia according to the Rome IV classification, were enrolled. They were randomly assigned to either the LJ88 or placebo group and instructed to ingest the test food (1 billion heat-killed LJ88 or placebo) once a day for six weeks. Gastroesophageal reflux-related symptoms were evaluated using FSSG scores as a primary endpoint. The Gastrointestinal Symptoms Rating Scale (GSRS), stomach state questionnaire, and serum gastrin concentration were used as secondary endpoints. In the FSSG evaluation, the heartburn score was significantly improved at 6 weeks in the LJ88 group compared to the placebo group. No severe adverse events related to the test food were observed. In conclusion, daily ingestion of heat-killed LJ88 improved temporal heartburn symptoms in non-diseased individuals.

The effects of Massa Medicata Fermentata on the digestive function and intestinal flora of mice with functional dyspepsia.

Introduction: The purpose of this study was to identify the chemical components of Massa Medicata Fermentata (MMF) in different fermentation methods, analyze its regulatory effects on gastrointestinal propulsion and intestinal flora in mice with food accumulation, and further explore its mechanism of action in the treatment of dyspepsia. Methods: The chemical compositions of three kinds of MMF were identified using the UPLC-Q- Exactive Orbitrap mass spectrometer. A model of spleen deficiency and food accumulation in mice was established. The gastric emptying rate and intestinal propulsion rate were calculated, serum gastrin concentration and cholinesterase activity were measured, and 16S rRNA microbial detection was performed in different groups of mouse feces. Results: The results showed that a total of 95 chemical components were identified from the three MMF extracts, 62 of which were the same, but there were differences in flavonoids and their glycosides, organic acids, and esters. MMF, PFMMF, and commercial MMF could all significantly improve the gastric emptying rate, intestinal propulsion rate, and GAS concentration in the serum of model mice; PFMMF has a better effect, while there was no significant difference in cholinesterase activity among the groups (p > 0.05). The 16S rRNA sequencing results showed that the MMF and PFMMF could increase the content of beneficial bacteria Bacteroidetes and decrease the pathogenic bacteria Verrucomicrobia in the intestines of model mice, while the commercial MMF could not. Discussion: Studies suggest that MMF has a variety of possible mechanisms for improving food accumulation and treating gastrointestinal dyspepsia, which provides reference value for the quality evaluation and clinical application of MMF.

The mechanism of folic acid on N-methyl-N’-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis through the PI3K/Akt pathway.

Chronic atrophic gastritis (CAG) is a precancerous atrophic gastritis of the stomach, which generates an urge to develop novel therapeu-tic schedules. This study aimed to investigate the effect of experimental folic acid administration on N-methyl-N’-nitro-N-nitrosoguanidine (MNNG)-induced CAG through the PI3K/Akt pathway in rats. The rats were divided into a Model Group, a Folic Acid Group and a Blank Group. Rats in the Model Group were induced by MNNG and given 10 mL/kg/d distilled water by gavage, while rats in the Folic Acid Group were induced by MNNG and given 5 mg/kg/d folic acid suspension by gavage. As a control, rats in the Blank Group were given the same amount of distilled water as MNNG and 10 mL/kg/d distilled water by gavage. The levels of gastrin (GAS) and motilin (MTL) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein ex-pressions were detected by quantitative polymerase chain reaction (q-PCR) and Western blot. According to hematoxylin and eosin (H&E) pathological analysis, there were inflammatory factors infiltration and derangement of mucosal epi-thelial cells in the model group, while the gastric tissue injury in the folic acid group was improved. Folic acid could decrease the content of GAS, increase the content of MTL in the serum of the rats, and regulate the expression of PI3K and AKT signal pathways. Folic acid can have a therapeutic effect on CAG by reducing the concentration of GAS in serum and increasing the concentration of MLT in serum. Our study would lay a theoretical foundation for using folic acid to investigate new therapies for CAG in humans.

Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes.

PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice. Healthy adult male BALB/c mice were randomly divided into three equal groups (n = 10 in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 μl saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of Sirt1, Pparg, Nfκb1 (p105), Nfe2l2, Cxcl5, Smad3, H2a.z, and H3f3b were measured by RT-PCR. The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in Sirt1, Pparg, and Cxcl5 mRNA expression. There were no differences in β-cell numbers between groups. Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of Sirt1, Pparg, and Cxcl5 in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced Cxcl5 mRNA expression and its association with pancreatic cancer risk should be investigated.

Serum gastrin concentrations in dogs with primary hyperparathyroidism.

Hypercalcemia has been associated with hypergastrinemia in humans. Hypergastrinemia could be responsible for gastrointestinal (GI) signs in dogs with primary hyperparathyroidism (PHPT). (a) Determine whether hypergastrinemia occurs in dogs with PHPT, (b) assess for potential correlations among ionized calcium (iCa), parathyroid hormone (PTH), and serum gastrin concentrations, and (c) determine whether gastrin concentrations decrease after management of PHPT. Phase 1: 151 client-owned dogs at the time of PHPT diagnosis, Phase 2: 24 dogs that underwent treatment for PHPT. Dogs with azotemia, concurrent disease, or those receiving acid suppressants were excluded. Twenty-four treated dogs had baseline and repeat quantification of serum gastrin, PTH, and iCa concentrations 4 weeks after treatment. The effect of treatment on gastrin, iCa, and PTH concentrations was assessed using Wilcoxon signed rank sum tests. Fisher exact testing was used to compare the proportion of dogs with hypergastrinemia in dogs with and without GI signs. Twenty-seven of 151 PHPT dogs (17.9%) had increased pre-treatment serum gastrin concentrations (median, 45.0 ng/L; interquartile range [IQR], 20.0 ng/L). Gastrin concentrations were not correlated with iCa (P = .92) or PTH (P = .60). Treatment of PHPT decreased PTH (P < .001) and iCa concentrations (P < .001), but not gastrin concentrations (P = .15). The proportion of dogs with hypergastrinemia with and without GI signs did not differ (P = 1.00). Mild increases in serum gastrin concentrations may be seen in dogs with PHPT, but this finding is independent of the presence of GI signs.

Elevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells

Micro-environmental factors, including stromal and immune cells, cytokines, and circulating hormones are well recognized to determine cancer progression. Melanoma cell growth was recently shown to be suppressed by cholecystokinin/gastrin (CCK) receptor antagonists, and our preliminary data suggested that melanoma patients with Helicobacter gastritis (which is associated with elevated serum gastrin) might have an increased risk of cancer progression. Therefore, in the present study, we examined how gastrin may act on melanoma cells. In 89 melanoma patients, we found a statistically significant association between circulating gastrin concentrations and melanoma thickness and metastasis, which are known risk factors of melanoma progression and prognosis. Immunocytochemistry using a validated antibody confirmed weak to moderate CCK2R expression in both primary malignant melanoma cells and the melanoma cell lines SK-MEL-2 and G361. Furthermore, among the 219 tumors in the Skin Cutaneous Melanoma TCGA Pan-Cancer dataset showing gastrin receptor (CCKBR) expression, significantly higher CCKBR mRNA levels were linked to stage III–IV than stage I–II melanomas. In both cell lines, gastrin increased intracellular calcium levels and stimulated cell migration and invasion through mechanisms inhibited by a CCK2 receptor antagonist. Proteomic studies identified increased MMP-2 and reduced TIMP-3 levels in response to gastrin that were likely to contribute to the increased migration of both cell lines. However, the effects of gastrin on tumor cell invasion were relatively weak in the presence of the extracellular matrix. Nevertheless, dermal fibroblasts/myofibroblasts, known also to express CCK2R, increased gastrin-induced cancer cell invasion. Our data suggest that in a subset of melanoma patients, an elevated serum gastrin concentration is a risk factor for melanoma tumor progression, and that gastrin may act on both melanoma and adjacent stromal cells through CCK2 receptors to promote mechanisms of tumor migration and invasion.

Gastric pH and serum gastrin concentration in age-matched healthy dogs and dogs with chronic kidney disease.

Gastric hyperacidity and hypergastrinemia are purported to cause gastric ulceration in dogs with chronic kidney disease (CKD); however, no published studies have evaluated gastric pH with serum gastrin concentrations in dogs with CKD. To compare mean intragastric pH, mean percent pH distribution, and serum gastrin concentrations in dogs with CKD to age-matched, healthy dogs. We hypothesized there would be no difference in mean gastric pH or serum gastrin between groups. Thirteen dogs with CKD; 10 aged-matched healthy dogs. Prospective, case-control study. Serum chemistry, complete blood count, urinalysis, and serum gastrin concentrations were evaluated in all dogs before radiographic-assisted gastric placement of a pH capsule. Forty-eight-hour continuous gastric pH monitoring was performed in all dogs. Serum gastrin concentration, mean pH, and mean percentage time that gastric pH was strongly acidic (pH <1 and pH <2) were compared between groups using a repeated measures mixed-model ANOVA. No significant differences were observed between groups for any pH measurements, including mean ± SD gastric pH (CKD, 2.37 ± 0.87; healthy, 2.39 ± 0.99; P > .05). Serum gastrin concentrations were not significantly different between groups (median [range]: CKD, 10.5 ng/dL [<10-17.1]; healthy, 10.9 ng/dL [<10-15]; P > .05). Our client-owned dogs with CKD did not have lower gastric pH or higher serum gastrin concentrations compared to healthy dogs. Our results suggest that prophylactic gastric acid suppression in dogs with CKD is not warranted unless other clinical indications for use are present.

Establishment of a reference interval for 12-hour fasted serum gastrin concentration in adult dogs.

Adherence to traditional 24-h fasting periods for serum gastrin concentration in dogs can be challenging and may delay the institution of therapies for suspected hypergastrinemia. Peer-reviewed publications regarding serum gastrin reference intervals (RI) are lacking. Hypercalcemia is associated with hypergastrinemia in people; limited data exist in dogs. The objective of the study was to generate a RI for a 12-h fasted serum gastrin concentration in dogs and to investigate whether correlations exist with age, weight, sex, and total calcium concentration. Fifty-five healthy adult dogs (>1 year of age). The screening included: medical history, physical examination, CBC (15 dogs), and serum chemistry (55 dogs). Gastrin was measured via a commercial radioimmunoassay. The RI for 12-h fasted serum gastrin concentration was calculated according to the recommendations of the American Society for Veterinary Clinical Pathology. Additionally, data were evaluated for correlation with selected variables. The RI for serum gastrin following a 12-h fasting period was 15.1-78.9 ng/L with 90% confidence intervals for the lower and upper limits of 14.0-22.9 and 68.3-83.0 ng/L, respectively. A generalized linear model did not detect significant relationships between gastrin and age (P = 0.48), sex (P = 0.30), weight (P = 0.93), or total calcium concentration (P = 0.84). A 12-h fasted serum gastrin concentration RI has been established. Given the limited range of serum calcium concentrations in our healthy study population, additional investigations are needed to determine the effects of hypercalcemia on serum gastrin concentrations in dogs and for any potential clinical consequences thereof.

Evaluation of the effects of medium-term (57-day) omeprazole administration and of omeprazole discontinuation on serum gastrin and serum chromogranin A concentrations in the horse.

Rebound gastric hyperacidity (RGH) secondary to hypergastrinemia has been suggested to contribute to the rapid recurrence of equine squamous gastric disease (ESGD) in horses after discontinuation of omeprazole. To evaluate changes in serum gastrin and chromogranin A (CgA) concentrations in response to medium-term (57-day) omeprazole treatment and after omeprazole discontinuation. Fourteen mature Thoroughbred racehorses in simulated race training. Horses received 2.28 g of oral omeprazole PO q24h for 57 days within a 61-day period, excluding a withholding period applied mid-protocol during which treatment was stopped as part of a concurrent study. Serum samples were collected on day 0 before omeprazole treatment, on day 1 of each week of the treatment period, and for an additional 5 weeks after discontinuation of treatment. Serum gastrin and CgA concentrations were analyzed using radioimmunoassay (RIA) and ELISA, respectively. Median serum gastrin concentrations increased 2.5-fold from baseline to day 7 (P < .001) but did not increase further during the omeprazole treatment period. Median serum gastrin concentrations returned to baseline within 2 to 4 days after administration of the last dose of omeprazole. No effect of treatment or discontinuation was seen in serum CgA concentrations. Serum gastrin concentrations increased in response to omeprazole treatment but returned to baseline within 2 to 4 days after the last dose of omeprazole. No effect of treatment or discontinuation was seen in serum CgA concentrations. Our results do not support the use of tapering protocols in horses.

Diagnostic performance of the normal range of gastrin calculated using strict criteria based on a combination of serum markers and pathological evaluation for detecting gastritis: a retrospective study

BackgroundThe ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate “patients without gastritis” (defined as true A patients) from those “with gastritis.” A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis.MethodsPatients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the “pathologically-evaluated group” and “endoscopically-evaluated group,” according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group.ResultsThe 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12–126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80.ConclusionThe gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future.

MELOXICAM-INDUCED GASTROPATHY IN DOGS: CLINICAL, BIOCHEMICAL, ENDOSCOPIC FEATURES AND TRIALS FOR PREVENTION

This study was conducted to evaluate and to compare the clinical, hemato-biochemical and endoscopic aspects of gastropathy in dogs treated with meloxicam alone or incombination with esomeprazole and misoprostol. Twenty baladi healthy dogs were included in the experimental study. Dogs were divided into four groups each group consisting of five animals; Group I (control group), the group that does not receive any medication. Meloxicam treated groups divided into: Group II which received meloxicam at a dose of 0.2 mg/kg BWT per OS /24 hr. Group III animals received the same previous dose of meloxicam and esomeprazole at a dose of 1mg/kg BWT per OS /24 hr. Group IV animals received the same dose of meloxicam and misoprostol 3μg /kg BWT per OS tid. Upon drug administration, dogs were kept under observation for 14 consecutive days. Clinical and hemato-biochemical analysis were evaluated across time (T0, T3, T7, T10 and T14). The image analysis of the gastroscopic examination was evaluated across time (T0, T7 and T14), endoscopic examinations were applied to all animals in four groups at three time points (T0, T7, and T14), endoscopic lesions were scored by use of a 5-point scale. Clinically, the most common clinical sings in dogs with Meloxicam induced- gastropathy were inappetence to anorexia, hematemesis, melena, abdominal pain and weakness, the specific endoscopic lesions of gastropathy were gastric erosion, hemorrhage and ulcers. Serum gastrin concentration is a biochemically sensitive indicator of gastropathy. The overall results concluded that meloxicam-induced gastropathy was more severe in group II compared to groups III and group IV. The proton pump inhibitor (esomeprazole) was more effective and better tolerated than misoprostol.

Effects of Proton Pump Inhibitor Therapy, H. pylori Infection and Gastric Preneoplastic Pathology on Fasting Serum Gastrin Concentrations.

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, p<0.0001), patients with active H. pylori infection (27pM, p<0.0001), and patients with antral (25pM, p<0.01) or corpus (48pM, p<0.0001) gastric preneoplasia. PPI use resulted in further significant increases in fasting serum gastrin concentrations in patients who were infected with H. 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.

A comparative time-dependent study of hematology, serum gastrin concentrations, and gastroscopic assessment of meloxicam-induced gastric ulceration in dogs.

BackgroundDiagnosis of gastric ulcers by methods other than gastroscopy in dogs has been problematic for many years and biomarkers such as serum gastrin (SG) concentrations have been introduced as a noninvasive way to evaluate gastric diseases.ObjectivesTo determine the time course changes in hematology, SG concentrations, and gastroscopic images of meloxicam‐induced gastric ulceration in dogs and identify a relationship between SG and gastroscopic image analysis in a clinical setting.AnimalsFifteen crossbreed dogs.MethodsTwo groups: control (n = 5) and meloxicam‐treated (n = 10). The meloxicam‐treated group received meloxicam 0.2 mg/kg PO for 15 days. Clinical signs, hematology, SG, and image analysis (PI, pixel intensity; ID, integrated density; RA, relative area; and UI, ulcer index) of the gastroscopic examination were evaluated across time (T5, time 5 day; T10, time 10 day; and T15, time 15 day).ResultsSignificant changes were observed among 3 time points and between the 2 groups in terms of SG, hematology, and gastroscopic image analysis. In the meloxicam‐treated group, decreases in hemoglobin concentration, red blood cell count and packed cell volume at T10 and T15 (P = .0001) were observed, whereas SG, ID, and UI increased over time (P < .0001). The PI decreased significantly (P = .0001) in the meloxicam‐treated group compared to controls. Significant correlations were found between SG and PI, and ID and ulcer area (r = −0.89, 0.81, 0.64), respectively.Conclusion and Clinical ImportanceGastroscopy is the gold standard for early descriptive diagnosis of gastric ulcerations in dogs, and SG is a good indicator for meloxicam‐induced gastric ulcers in dogs and can predict the gastroscopic score of the lesion.

White Spot, a Novel Endoscopic Finding, May Be Associated with Acid-Suppressing Agents and Hypergastrinemia.

White globe appearance (WGA) is defined as a microendoscopic white lesion with a globular shape underlying the gastric epithelium and is considered a marker of gastric cancer. We recently reported that endoscopically visualized white spot (WS) corresponding to WGA appeared on the nonatrophic mucosa of patients with acid-suppressing agents (A-SA) use. We evaluated patients undergoing routine esophagogastroduodenoscopy and divided the patients into an A-SA group (n = 112) and a control group (n = 158). We compared the presence of WS in both groups. We also compared WS-positive- (n = 31) and -negative (n = 43) groups within the A-SA group regarding these patients’ backgrounds and serum gastrin concentrations. Comparing the A-SA group with controls, the prevalence of WS was significantly higher (31/112 vs. 2/158; p < 0.001). The number of patients with high serum gastrin concentrations was significantly higher in the WS-positive group (18/31) vs. the WS-negative group (5/43) (p < 0.001). Within the A-SA group, the prevalence of WS was also significantly higher in patients taking potassium-competitive acid blockers vs. proton-pump inhibitors (21/31 vs. 10/31, p < 0.001). The WS-positive group had a significantly greater percentage of patients, with a high serum gastrin level (p < 0.001). WS may be associated with hypergastrinemia and potassium-competitive acid blockers.

Metastatic Non-Functional Pancreatic Neuroendocrine Tumor in a Patient With a Pathogenic TSC1 Mutation

Abstract Introduction: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder caused by mutations in two tumor suppressor genes (TSC1 and TSC2) encoding proteins critical in cell growth and proliferation and is associated with an increased risk for benign and malignant tumors. Pancreatic neuroendocrine tumors (PNET) occur in 1.5-1.8% of patients with TSC. They have been primarily reported in TSC2, with only a few cases in the context of TSC1. We describe a non-functional metastatic PNET in a patient with a known pathogenic TSC1 mutation. Case Description: A 49-year old female with a past medical history of bipolar disease, a family history of TSC1 in a daughter, a known pathologic TSC1 mutation (c.2356C&amp;gt;T), and previous history of renal cell carcinoma (RCC) was evaluated for a pancreatic lesion with likely liver metastases. Two years prior to the presentation, a 10 mm pancreatic lesion was initially noted on the CT scan during a renal mass evaluation. Nephrectomy confirmed the RCC. Two years later, surveillance imaging revealed two new lesions in the liver, and the pancreatic lesion had enlarged to 1.3 cm. She denied symptoms suggestive of a functional PNET, and her physical exam was unremarkable. Gallium-68 dotatate (GA-68) PET/CT scan demonstrated avid lesions of both the pancreatic tail and left hepatic lobe. Biopsy of the 3 cm liver mass revealed a metastatic high-grade neuroendocrine carcinoma (mib-1 proliferation index of 15%) favoring a primary PNET. Immunohistochemical stains were positive for chromogranin A, synaptophysin, EMA, PAX 8, CK 20, and villin. Stains for CA 19-9 and CK 7 were negative. Biochemical testing suggested that the PNET was non-functional. Specifically, serum concentrations of gastrin, somatostatin, glucagon, glucose, C-peptide, proinsulin, pancreatic polypeptide, chromogranin A, and vascular endothelial growth factor were within normal limits. The patient underwent distal pancreatectomy and resection of the liver mass. Pathological specimens confirmed the diagnosis of a PNET. The patient remained asymptomatic and was monitored regularly with MRI and GA-68 PET/CT scans without further evidence of the disease for 1.5 years. Conclusions: We conclude that this patient harboring a c.2356C&amp;gt;T TSC1 mutation developed a non-functional metastatic PNET. PNET is a likely component of TSC1.

Primary hepatic gastrinoma being diagnosed preoperatively: a case report and literature review

BackgroundA majority of gastrinomas causing Zollinger–Ellison syndrome are located in the duodenum or pancreas. Primary hepatic gastrinomas are rare and difficult to diagnose. We report a rare case of primary hepatic gastrinoma, which could be diagnosed preoperatively.Case presentationA 29-year-old man with a 55-mm tumor in segments 5 and 6 (S 5/6) of the liver was admitted to our hospital. After thorough investigations, he was treated for a suspected inflammatory pseudotumor and advised to undergo routine follow-up. Two years later, he revisited our hospital with a complaint of abdominal pain, vomiting, and diarrhea. Upper gastrointestinal endoscopy revealed multiple duodenal ulcers. His serum gastrin level was 2350 pg/mL (normal: 37–172 pg/mL), suggesting Zollinger–Ellison syndrome. Abdominal computed tomography showed a 78-mm hypervascular tumor with cystic degeneration in the S 5/6 region of the liver, with a potential to increase over time. The tumor showed hypointensity on T2-weighted and hyperintensity on diffusion-weighted abdominal contrast-enhanced magnetic resonance imaging. Somatostatin receptor scintigraphy (SRS) only detected a hepatic tumor. No tumors in the gastrinoma triangle were detected by endoscopic ultrasonography. Hence, selective arterial calcium injection (SACI) test was performed to determine the location of the gastrinoma. The serum gastrin concentration increased from 4620 pg/mL to 23,600 pg/mL at 20 s after calcium gluconate injection into the proper hepatic artery. Conversely, no effect on serum gastrin level was observed after the injection into any other arteries. Extended right hepatic lobectomy and cholecystectomy were performed after percutaneous transhepatic portal vein embolization. A histopathological examination of the liver tumor revealed a gastrinoma. The patient’s serum gastrin concentration on postoperative day 1 decreased to 65 pg/mL.ConclusionWe report a surgical case of primary hepatic gastrinoma correctly diagnosed preoperatively. The patient underwent extended right hepatic lobectomy, resulting in a histological definitive diagnosis of primary hepatic gastrinoma.

The effect of porcine hydrolysed collagen on gastric ulcer scores, gastric juice pH, gastrin and amino acid concentrations in horses

SummaryGastric ulcers are common in horses. The purpose of this study was to test the effect of porcine hydrolysed collagen (PHC) on gastric ulcer scores and gastric juice pH in horses. We hypothesise that PHC‐administration will result in improved gastric lesion scores and act synergistically with omeprazole to improve treatment efficacy. Thoroughbred horses (n = 10) were studied in a 2‐period, 2‐treatment crossover design, where the PHC (45 g) was administered twice daily. Horses were treated for 56 days. Gastroscopy was performed and gastric juice pH measured on Days 0, 14, 28, 42, 49 and 56. Nonglandular gastric ulcer number (NGN) and severity (NGS) and glandular ulcer number (GN) and glandular severity (GS) scores were assigned by an investigator masked to treatment and serum gastrin and amino acid concentrations. By Day 42, 2 weeks after discontinuing omeprazole treatment, NGN and NGS scores returned to pretreatment values and serum gastrin was higher when compared to values measured on Day 28. By Day 49, after the feed‐deprivation period, NGN and NGS were similar to pretreatment values. By Day 56, mean NGN score was significantly lower in PHC‐treated horses, compared to controls. Mean gastric juice pH significantly increased in both groups on Day 28 and the pH was significantly (P = 0.0127) higher in the PHC‐treated horses. Serum amino acid concentrations were not significantly different 2 h after feeding PHC and hydroxyproline was not detected. Serum gastrin concentration did not increase 2 h after feeding in the PHC‐fed horses. The PHC fed to horses enhanced the effects of omeprazole on increased gastric juice pH, inhibited gastrin secretion after feeding and resulted in fewer nonglandular ulcers after long‐term feeding (56 days) in stall‐confined horses undergoing intermittent feeding.

Serum pepsinogen and gastrin concentrations in South American camelids with and without gastrointestinal nematode infection

Abstract Endoparasitosis is one of the major health problems in South American camelids (SACs) often leading to massive damage of the gastric or intestinal mucosa. In ruminants this damage results in increased gastrin and pepsinogen concentrations in the peripheral blood. These values have been used as diagnostic parameters for subclinical gastrointestinal nematode infections in ruminants but have not been systemically studied in SACs. Serum pepsinogen and gastrin concentrations of 183 clinically healthy SACs with and without detectable parasitic egg excretion and the occurrence of occult blood in the faeces were determined. The median (1st/3rd quartile) of serum pepsinogen and gastrin were 1899.4 (1483.1/2749.4) ng/ml and 184.8 (121.8/340.5) pg/ml for alpacas; 1642.0 (1182.3/2608.7) ng/ml and 191.8 (142.2/287.6) pg/ml for llamas respectively. A sensitivity of 80.1 % and a specificity of 11.1 % for gastrin (cut off 402 pg/ml) and a sensitivity of 64.1 % and specificity of 88.9 % for pepsinogen with endoparasitosis (cut off 1996 ng/ml) were calculated. Based on our results, albeit on quite small numbers, determination of serum gastrin concentration does not seem to be a useful test for the detection of endoparasitic infection in SACs. In contrast, for pepsinogen a correlation was found between serum concentration and animals with and without endoparasitosis. Nevertheless further studies are necessary in order to investigate the diagnostic potential of pepsinogen serum concentration in relation to subclinical endoparasitosis.