Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

Calcitonin levels in autoimmune atrophic gastritis-related hypergastrinemia.

PURPOSE: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels. METHODS: Three groups of patients were consecutively enrolled in this  multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females). RESULTS: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785). CONCLUSIONS: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG.

Gastrin and the Moderate Hypergastrinemias.

The antral hormone gastrin potently regulates gastric acid secretion and fundic mucosal growth. Consequently, appropriate gastrin secretion and plasma concentrations are important for the early phases of digestion. This review describes as the first premise the normal biogenesis of gastrin in the antral mucosa, but also mentions the extraantral expression. Subsequently, the molecular nature and concentration levels of gastrin in serum or plasma are overviewed. Third, assays for accurate measurements of plasma or serum concentrations are commented. Finally, the problem of moderate hypergastrinemia due to Helicobacter pylori infections and/or treatment with proton-pump inhibitors (PPI) is discussed. The review concludes that accurate measurement of the true concentrations of bioactive gastrins in plasma is important. Moreover, it suggests that moderate hypergastrinemias are also essential health issues that require serious attention.

Gastric Neuroendocrine Tumors (Carcinoids).

PURPOSE OF REVIEW: The diagnosis of gastric neuroendocrine tumors (NETs) is being made with increased frequency likely as a result of more upper endoscopies being done for unrelated reasons. It is therefore vital that gastroenterologists become familiar with the basic work-up and management of patients found to have these tumors. This review describes the classification, pathophysiology, clinical characteristics, and treatment options of the different gastric NETs. RECENT FINDINGS: In addition to the three traditional subtypes of gastric NETs, additional cases associated with achlorhydria and appropriate hypergastrinemia may exist. The management of gastric NETs between 1 and 2 cm in size remains controversial and needs to be individualized. Gastric NETs are uncommon but are now diagnosed more frequently. This review highlights the role of hypergastrinemia in their development and the controversies around their management.

Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome.

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

Strategies for Effective Discontinuation of Proton Pump Inhibitors.

PURPOSE OF REVIEW: Proton pump inhibitors (PPIs) are effective for many conditions but are often overprescribed. Recent concerns about long-term risks have made patients re-evaluate their need to take PPIs chronically, though these population-based studies have methodological weaknesses. The goal of this review is to provide evidenced-based strategies for discontinuation of PPI therapy. RECENT FINDINGS: Given that some patients experience rebound symptoms when abruptly stopping continuous PPI therapy due to its effect on hypergastrinemia, strategies focus on avoiding rebound. Tapering the PPI and then initiating a "step-down" approach with the use of alternative medications may be effective. "On-demand therapy" provides patients with the option to take intermittent PPI courses, reducing overall use and cost while preserving patient satisfaction. It is important for providers to consider ambulatory pH or pH/impedance testing to rule out diagnoses that may require alternative medications like neuromodulators. A number of studies reviewed here can provide guidance in counseling patients on PPI discontinuation. It is important for the provider to obtain a baseline needs assessment for PPI therapy and to elucidate predictors of difficulty in discontinuation prior to initiating a strategy.

Does the Novel Potassium-Competitive Acid Blocker Vonoprazan Cause More Hypergastrinemia than Conventional Proton Pump Inhibitors? A Multicenter Prospective Cross-Sectional Study.

BACKGROUND/AIM: The long-term administration of proton pump inhibitors (PPIs) is useful for preventing recurrent reflux esophagitis. On the other hand, several adverse reactions, such as an increase in the blood gastrin level, have been reported. The aim of the present study was to examine the increase in the blood gastrin level due to the long-term administration of conventional PPIs compared with vonoprazan. METHODS: A prospective cross-sectional study was conducted. We examined the blood gastrin levels of patients taking vonoprazan or conventional PPIs in whom the grade of atrophic gastritis had been endoscopically evaluated in the last year. RESULTS: The blood gastrin level was significantly higher in the vonoprazan group than that in the PPI group in patients with milder or no atrophic gastritis, irrespective of the administration periods. However, no significant difference was observed between the groups in patients with severe atrophic gastritis. CONCLUSION: Vonoprazan more markedly increased the blood gastrin level compared with conventional PPIs in patients with milder or no atrophic gastritis. This indicates that vonoprazan may have stronger acid-suppressing effects in such patients than conventional PPIs. Key Message: We should be aware of the potential development of hypergastrinemia during the long-term administration of vonoprazan, especially in patients with mild or no atrophic gastritis.

Old and New Gut Hormone, Gastrin and Acid Suppressive Therapy.

Gastrin acts physiologically as a gut hormone to stimulate acid secretion after meal and as a cell-growth factor of oxyntic mucosa. Increase in serum gastrin level happens under various conditions including Zollinger-Ellison syndrome, antral G cell hyperplasia, autoimmune gastritis, atrophic gastritis, renal failure, vagotomy, Helicobacter pylori infection and acid suppressive therapy. As acid suppressive therapy causes hypergastrinemia, the association between acid suppressive therapy and gastric neuroendocrine cell tumor (NET) has been discussed during the past 30 years. In this review article, the definition of hypergastrinemia and the related disorders including acid suppressive therapy and gastric NET are discussed.

A case of type 1 multiple endocrine neoplasia with esophageal stricture successfully treated with endoscopic balloon dilation and local steroid injection combined with surgical resection of gastrinomas.

BACKGROUND: In type 1 multiple endocrine neoplasia (MEN1), esophageal diseases association with excessive gastrin secretion in Zollinger-Ellison syndrome (ZES) sometimes develop. Here, we reported a case of MEN1/ZES, who developed dysphagia due to reflux esophagitis with severe esophageal stricture. Treatment for his esophageal stricture and ZES was discussed. CASE PRESENTATION: A 43-year-old man with progressive dysphagia and diarrhea was referred to the teaching hospital. He had a history of recurrent duodenojejunal perforations despite the anti-secretory medication. Blood examinations revealed elevated serum gastrin, calcium, and parathyroid hormone. Upper gastrointestinal endoscopy demonstrated a severe esophageal stricture, multiple gastroduodenal ulcer scars, and a duodenal submucosal tumor. Enhanced computed tomography showed multiple hypervascular tumors within the pancreas and duodenum, suggestive of MEN1. Genetic examination demonstrated a pathogenic MEN1 mutation. Repetitive endoscopic esophageal dilatation with intralesional corticosteroid injection, coupled with pancreatoduodenectomy were performed to improve the patient's symptoms and to treat pancreatic tumors. The histology of multiple tumors in the duodenum and pancreas were all consistent with neuroendocrine tumors. His hypergastrinemia subsided and he remained asymptomatic in his gastrointestinal tract after these treatments. CONCLUSION: For esophageal stenosis in case of MEN1/ZES, anti-secretory therapy and endoscopic dilatation with corticosteroid injection could be recommended. However, in refractory cases with repetitive and/or severe complications due to high acid secretion, surgical treatment could be considered as an option.

Catching the Zebra: Clinical Pearls and Pitfalls for the Successful Diagnosis of Zollinger-Ellison Syndrome.

Zollinger-Ellison syndrome (ZES) results from an ectopic gastrin-secreting tumor leading to peptic ulcer disease, reflux, and chronic diarrhea. While early recognition portends an excellent prognosis with >80% survival at 15 years, symptoms are often nonspecific making the diagnosis difficult to establish. Diagnosis involves a series of tests, including fasting gastrin, gastric pH, chromogranin A, and secretin stimulation. Performing these tests in the correct sequence and at the proper time is essential to avoid inaccurate results. Tumor localization is equally nuanced. Although providers have classically used 111indium-radiolabeled octreotide with somatostatin receptor scintigraphy to evaluate tumor size and metastases, recent studies have shown superior results with newer imaging modalities. In particular, 68gallium (68Ga)-labeled somatostatin radiotracers (i.e., 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE) used with positron emission tomography/computed tomography can provide excellent results. Endoscopic ultrasound is another useful modality, particularly in patients with ZES in the setting of multiple endocrine neoplasia type 1. This review aims to provide clinicians with an overview of ZES with a focus on both clinical presentation and the proper utilization of the various biochemical and imaging tests available.

Effect of gastric acid-suppressive therapy and biological variation of serum gastrin concentrations in dogs with chronic enteropathies.

BACKGROUND: Serum gastrin concentration can help diagnose gastrinomas in dogs if >3-10× the upper reference limit (URL), but antisecretory therapy and other conditions can also cause hypergastrinemia. Effects of antisecretory therapy (famotidine or ranitidine, omeprazole) on serum gastrin concentration in dogs with chronic enteropathy (CE) and its biological variation (BV) are unknown. Aim of the study was to evaluate serum gastrin in acid-suppressant-treated or -naïve CE dogs; test the association between serum gastrin and histopathologic findings in acid-suppressant-naïve CE dogs; and evaluate the BV of serum gastrin in dogs not receiving any gastric acid suppressive therapy. Samples from 231 dogs were used and serum gastrin was measured by chemiluminescence assay. Gastric and duodenal histologic lesions were evaluated and graded. BV of serum gastrin was evaluated in serial samples. RESULTS: Serum gastrin concentrations were significantly higher in acid-suppressant-treated than acid-suppressant-naïve dogs (P = 0.0245), with significantly higher concentrations in proton pump inhibitor (PPI)- than H2-antihistamine-treated patients (P = 0.0053). More PPI- than H2-antihistamine-treated dogs had gastrin concentrations above URL (P = 0.0205), but not >3× nor >10× the URL. Serum gastrin concentrations correlated with the severity of gastric antral epithelial injury (P = 0.0069) but not with any other lesions or the presence/numbers of spiral bacteria in gastric biopsies. Intra- and inter-individual BV were 43.4 and 21.6%, respectively, in acid-suppressant-naïve dogs, with a reciprocal individuality index of 0.49 and a critical difference of ≥29.5 ng/L. CONCLUSIONS: Antisecretory (particularly PPI) treatment leads to hypergastrinemia in CE dogs, but the concentrations seen in this study are unlikely to compromise a diagnosis of gastrinoma. Use of a population-based URL for canine serum gastrin and a URL of ≤27.8 ng/L are appropriate.

Assessment of Gastric Emptying in Patients with Autoimmune Gastritis.

BACKGROUND AND AIM: Symptoms of patients with autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any delay in gastric emptying of solid food exists in patients with autoimmune gastritis and, if so, to identify the factors that might affect delayed gastric emptying. METHODS: A total of 165 patients (106 women) diagnosed as having autoimmune gastritis were analyzed by means of a gastric emptying test. All patients underwent a standardized scintigraphic gastric emptying study. Patients with delayed gastric emptying and normal gastric emptying tests were then compared by means of factors that might affect gastric emptying. Also 65 patients with functional dyspepsia who had a gastric emptying study constituted the control group. RESULTS: The median gastric emptying T ½ time was 127.43 min (min-max 50-953) for patients with AIG and 81 min (min-max 21-121.6) for functional dyspepsia patients (p < 0.001), and median percent retention at 2 h was 63.8 versus 20.2 (p < 0.001). In multivariate analysis, parameters that affected gastric emptying T ½ time were found as serum gastrin level (OR 1.002, 95 % CI 1.001-1.004, p < 0.001, chronic inflammation (OR 3.689, 95 % CI 1.44-9.39, p < 0.001), and increase in the degree of the atrophy of the gastric mucosa (OR 8.96, 95 % CI 2.98-26.93, p < 0.001). CONCLUSIONS: In patients with autoimmune gastritis, gastric emptying is generally delayed. Autoimmune gastritis is an important etiology to explain the finding of delayed gastric emptying on a radionuclide test. This new finding is likely to be relevant to clinicians when evaluating and initiating appropriate medical treatment for patients with autoimmune gastritis manifesting upper gastrointestinal symptoms.

Relationships between autonomic nerve function and gastric emptying in patients with autoimmune gastritis.

PURPOSE: Autonomic nervous system dysfunction exists in autoimmune diseases. Symptoms of autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any autonomic dysfunction exists in autoimmune gastritis patients, and if so, to clarify the relationship between the autonomic nervous dysfunction, delayed gastric emptying, and gastrointestinal symptoms. METHODS: 75 patients (50 women, mean age 56.73 ± 11.77) diagnosed with autoimmune gastritis were investigated by means of autonomic nervous system and gastric emptying tests. All patients underwent a standardized scintigraphic gastric emptying study and five tests evaluating autonomic nervous system. Patients with autonomic nervous system dysfunction were then analyzed and compared by means of existence of delayed gastric emptying and gastrointestinal symptoms. RESULTS: 62 patients had autonomic nervous system dysfunction (14 mild, 40 moderate, and 8 severe autonomic dysfunction). The mean total score of autonomic tests was 3.85 ± 2.35. Total autonomic score of patients (n = 60) with delayed gastric emptying was significantly higher than patients (n = 15) with normal gastric emptying (4.68 ± 1.7 vs. 1.53 ± 0.58, p < 0.001). Mean gastroparesis cardinal symptom index was significantly higher in patients (n = 60) with delayed gastric emptying half-time compared to patients (n = 15) with normal gastric emptying half-time (1.89 ± 1.16 vs 0.4 ± 0.3, p < 0.001). CONCLUSIONS: Most of patients with autoimmune gastritis also have autonomic nerve dysfunction. There is a close relationship between autonomic nervous system dysfunction and delayed gastric emptying. Gastroparesis cardinal symptom index has a high sensitivity and specificity in predicting both autonomic nerve function and delay in gastric emptying.

Gastric neuroendocrine tumors: prevalence in Europe, USA, and Japan, and rationale for treatment with a gastrin/CCK2 receptor antagonist.

OBJECTIVE: Gastric carcinoids (neuroendocrine tumors) arise from enterochromaffin-like cells in the gastric mucosa. Most are caused by hypergastrinemia. The objectives were to determine if their prevalence in Europe, USA and Japan meets the criteria for an orphan disease and to justify treatment with a gastrin/CCK2 receptor antagonist. METHODS: We obtained data from European and USA cancer registries, and searched PubMed. RESULTS: Prevalence per 10,000 population obtained from cancer registries was: median 0.32 (range 0.09-0.92) for Europe; and 0.17 for the USA, equivalent to 4812 for the whole population. A PubMed search for gastric carcinoids yielded prevalence for Japan only, which was 0.05 per 10,000 population, equivalent to 665 for the entire population. A further search for gastric carcinoids in patients with pernicious anemia (PA) or autoimmune chronic atrophic gastritis (CAG), two presentations of about 80% of gastric carcinoids, produced prevalence rates of 5.2-11%. Prevalence of PA itself was 0.12-1.9%. Data on CAG epidemiology were sparse. CONCLUSION: Prevalence of gastric carcinoids varied widely. All sources probably underestimate prevalence. However, prevalence was below the limits required for recognition by drug regulatory authorities as an orphan disease: 5 per 10,000 population of Europe; 200,000 for the whole population of the USA; and 50,000 for the whole population of Japan. Because gastric carcinoids are an orphan disease, and nonclinical and healthy volunteer studies support treatment with netazepide, a gastrin/CCK2 antagonist, netazepide has been designated an orphan medicinal product in Europe and the USA for development as targeted treatment for gastric carcinoids.

G-cell hyperplasia of the stomach induces ECL-cell proliferation in the pyloric glands in a paracrinal manner.

An inhibitory mechanism toward gastrin hypersecretion is significantly different between G-cell hyperplasia and gastrinoma despite the common clinical manifestations; hypergastrinemia and its related persistent gastric ulcers. We recenlty studied the G-cell, d-cell and ECL-cell density in a case of G-cell hyperplasia. The 70-year-old patient has been treated for persistent gastric ulcers with a markedly increased plasma gastrin (5600 pg/mL). The stomach was surgically resected because of the obstruction associated with ulcer scars. The number of G-cells in the pyloric glands was quantified on the surgical specimens and G-cell hyperplasia was histolopathologically identified. Immunostainig of histidine decarboxylate revealed the presence of ECL-cell hyperplasia in the pyloric glands and its density was significantly and positively correlated with G-cell density. Somatostatin immunoreactive cells (D-cells) increased in their number in the oxyntic glands. These results all indicated that hypersecretion of gastrin in G-cell hyperplasia could induce ECL-cell proliferation in a paracrinal manner. In addition, relatively non-prominent endocrinological features in the G-cell hyperplasia compared to gastrinoma could be also related to the paracrinal somatostatin inhibitory effects upon ECL-cells in the pyloric glands.

Consensus diagnoses and mode of action for the formation of gastric tumors in rats treated with the chloroacetanilide herbicides alachlor and butachlor.

A panel of pathologists (Panel) was formed to evaluate the pathogenesis and human relevance of tumors that developed in the fundic region of rat stomachs in carcinogenicity and mechanistic studies with alachlor and butachlor. The Panel evaluated stomach sections stained with hematoxylin and eosin, neuron-specific enolase, and chromogranin A to determine the presence and relative proportion of enterochromaffin-like (ECL) cells in the tumors and concluded all tumors were derived from ECL cells. Biochemical and pathological data demonstrated the tumor formation involved a nongenotoxic threshold mode of action (MOA) initially characterized by profound atrophy of the glandular fundic mucosa that affected gastric glands, but not surface epithelium. This resulted in a substantial loss of parietal cells and a compensatory mucosal cell proliferation. The loss of parietal cells caused a marked increase in gastric pH (hypochlorhydria), leading to sustained and profound hypergastrinemia. The mucosal atrophy, together with the increased gastrin, stimulated cell growth in one or more ECL cell populations, resulting in neoplasia. ECL cell autocrine and paracrine effects led to dedifferentiation of ECL cell tumors. The Panel concluded the tumors develop via a threshold-dependent nongenotoxic MOA, under conditions not relevant to humans.

Serum gastrin concentrations in dogs with primary hyperparathyroidism.

BACKGROUND: Hypercalcemia has been associated with hypergastrinemia in humans. Hypergastrinemia could be responsible for gastrointestinal (GI) signs in dogs with primary hyperparathyroidism (PHPT). HYPOTHESIS/OBJECTIVES: (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. ANIMALS: Phase 1: 151 client-owned dogs at the time of PHPT diagnosis, Phase 2: 24 dogs that underwent treatment for PHPT. METHODS: 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. RESULTS: 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). CONCLUSIONS AND CLINICAL IMPORTANCE: Mild increases in serum gastrin concentrations may be seen in dogs with PHPT, but this finding is independent of the presence of GI signs.

A Case of Brunner's Gland Hyperplasia Accompanied by an Increase in Endocrine Cells and Endocrine Cell Micronests.

Endocrine cell micronests (ECMs) are aggregates of endocrine cells known as enterochromaffin-like cells, typically measuring approximately 50 µm and usually observed in the mucosal layer of atrophic gastric fundic glands associated with hypergastrinemia. Although there are numerous reports on gastric ECMs, reports on duodenal ECMs are exceedingly rare. We report a rare case of Brunner's gland hyperplasia with increased endocrine cells and ECMs. An approximately 40 mm polyp was found in the duodenal bulb of a 57-year-old Japanese male patient during an upper gastrointestinal endoscopy, and a polypectomy was performed. Microscopic examination revealed hyperplasia of Brunner's glands in the duodenal polyp. Compared to normal Brunner's glands, hyperplastic Brunner's glands exhibited more endocrine cells. Additionally, many ECMs were observed in the fibromuscular connective tissue, comprising smooth muscle cells and myofibroblasts, adjacent to the hyperplastic Brunner's glands. The patient presented with hypergastrinemia (2,500 pg/mL; normal range: 30-140 pg/mL), and the ECMs were considered related to this condition. This case represents the first instance of a benign duodenal lesion with an increase in endocrine cells and the presence of ECMs.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Effect of Proton Pump Inhibitor Use on Survival of Patients With Colorectal Cancer: A Study of a Racially Diverse Population.

Introduction Proton pump inhibitor (PPI) use is increasing in the general population. Chronic PPI use can lead to hypergastrinemia, which has been purported to increase the risk of developing colorectal cancer (CRC). Several studies have failed to report any association between PPI use and the risk of CRC. However, little is known about the effect of PPI use on CRC survival. In this retrospective analysis, we studied the effect of PPI use on CRC survival in a racially diverse population. Methods Data were abstracted for 1050 consecutive patients diagnosed with CRC from January 2007 to December 2020. The Kaplan-Meier curve was created to study the effect of PPI exposure compared to no exposure on overall survival (OS). Univariate and multivariate analyses were performed to investigate predictors of survival. Results Complete data were available for 750 patients with CRC, 52.5% were males, 22.7% were Whites, 60.1% were Asians, and 17.2% were Pacific Islanders. A total of 25.6% of patients had a history of PPI use. Moreover, 79.2% had hypertension, 68.8% had hyperlipidemia, 38.0% had diabetes mellitus, and 30.2% had kidney disease. There was no difference in median OS among PPI users compared to non-users, p value=0.4. Age, grade, and stage were predictors of inferior OS. No significant association was noticed with gender, race, comorbidities, or treatment with chemotherapy. Conclusion In this retrospective analysis of a racially diverse population of CRC patients, we found that PPI use was not associated with worse OS. Until high-quality prospective data are available, physicians should not stop PPIs that are clinically indicated.