Gastric Acid Hypersecretion Research Articles

The effect of mebeverine in extended-release capsules on intestinal motor function in patients with functional gastrointestinal pathology

Purpose of the study. Evaluation of the clinical effectiveness of combination therapy for FGID with overlap syndrome – gastroesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) using the PPI omeprazole and the myotropic antispasmodic mebeverine hydrochloride in extended-release capsules (Meberin ML, Micro Labs Limited, India) on clinical manifestations and motor-evacuation function of the gastrointestinal tract in patients with FGID with overlap syndrome – GERD, FD with gastric hypersecretion and IBS.Materials and methods. We examined 27 patients with FGID with overlap syndrome of GERD, FD with gastric hypersecretion of hydrochloric acid and IBS.Results and conclusion. It has been established that combination therapy with these drugs for two weeks in 97 % of cases eliminates the clinical symptoms of the syndromes, improves the quality of life of patients, normalizes intestinal motility and myoelectric activity of the gastrointestinal tract.

Sporadic gastrinoma with refractory benign esophageal stricture: A case report

BACKGROUND Gastrinoma is characterized by an excessive release of gastrin, leading to hypersecretion of gastric acid, subsequently resulting in recurrent peptic ulcers, chronic diarrhea, and even esophageal strictures. This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture (RBES). Additionally, it highlights the persistent challenges that gastroenterologists encounter in managing RBES. CASE SUMMARY This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy, multiple endoscopic bougie dilations and endoscopic incisional therapy (EIT). CONCLUSION It is essential to diagnose gastrinoma as early as possible, as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures. In patients with esophageal strictures causing complete luminal obstruction, blind reopening EIT presents challenges and carries a high risk of perforation.

Clinical Dilemma Involving Treatments for Very Low-Birth-Weight Infants and the Potential Risk of Necrotizing Enterocolitis: A Narrative Literature Review.

Necrotizing enterocolitis (NEC) is a critical gastrointestinal emergency with substantial morbidity and mortality risks, especially for very low-birth-weight (VLBW) infants, and unclear multifactorial pathophysiology. Whether common treatments for VLBW infants increase the NEC risk remains controversial. Indomethacin (utilized for patent ductus arteriosus) offers benefits but is concerning because of its vasoconstrictive impact on NEC susceptibility. Similarly, corticosteroids used to treat bronchopulmonary dysplasia may increase vulnerability to NEC by compromising immunity and altering the mesenteric blood flow. Histamine-2 receptor blockers (used to treat gastric bleeding) may inadvertently promote NEC by affecting bacterial colonization and translocation. Doxapram (used to treat apnea) poses a risk of gastrointestinal disturbance via gastric acid hypersecretion and circulatory changes. Glycerin enemas aid meconium evacuation but disrupt microbial equilibrium and trigger stress-related effects associated with the NEC risk. Prolonged antibiotic use may unintentionally increase the NEC risk. Blood transfusions for anemia can promote NEC via interactions between the immune response and ischemia-reperfusion injury. Probiotics for NEC prevention are associated with concerns regarding sepsis and bacteremia. Amid conflicting evidence, this review unveils NEC risk factors related to treatments for VLBW infants, offers a comprehensive overview of the current research, and guides personalized management strategies, thereby elucidating this clinical dilemma.

Evaluation of the acid-neutralizing and cytotoxicity properties of novel plant mucilage used as an alternative treatment for peptic ulcers and as antacids in Namibia

Hypersecretion of gastric acid damages the stomach lining, causing the formation of peptic ulcers. Mucilage from medicinal plants offers a relaxing and soothing effect to the endodermal lining of the gut and has antacid properties, which can protect the mucosal lining from gastric acidity. This is the first report aimed to evaluate the physicochemical characteristics, acid-neutralizing, and cytotoxicity properties of traditionally used aqueous mucilage from Asparagus exuvialis and Sesamum capense. The physicochemical properties were determined by biochemical methods. Acid neutralizing and buffering capacities were determined by titration methods. Normal mouse embryonic fibroblast cells were used for cytotoxicity evaluation by MTT assay. The physicochemical characterization confirmed the presence of carbohydrates, alkaloids, saponins, proteins, tannins, flavonoids, and glycosides. Sesamum capense mucilage exhibited the most potent artificial gastric juice neutralizing capacity pH of 4.62±0.01, 8.0±0.00 acid neutralization capacity per gram of acid, and 30 minutes duration of acid neutralization. The aqueous mucilage from S. capense did not cause any significant cytotoxicity to 3T3 cell lines showing an IC50 value of 91.5 ± 0.06 μg mL-1, confirming the safe nature of the mucilage. These findings revealed that S. capense has the potential to neutralize gastric acid responsible for ulceration and can be safely consumed.

Evaluation of Hydro-alcoholic extract of Corchorus capsularis seeds for its Anti-ulcer activity on Albino Wistar Rat

The objective of present study was to evaluate the anti-ulcer activity of hydro-alcoholic extract of Corchorus capsularis seeds. Mainly hyper secretion of gastric acid and pepsin causes ulcer in patients. Plant extracts and polyherbal formulations are two of the most appealing sources of new drug. This type of extract formulations are showing good results in the treatment of gastric ulcers. In this study anti-ulcer activity was investigated by pyloric ligation, aspirin and stress induced gastric ulcer in albino wistar rats. The extract was given at the dose of 250mg/kg (CCLD- Corchorus capsularis low dose) and 500mg/kg (CCHD- Corchorus capsularis high dose) in all the experimental models. Ranitidine (150mg/kg) was used as standard drug. CCLD and CCHD showed 37.49% and 63.14% ulcer inhibition respectively, whereas ranitidine 69.69% against pylorus ligation induced ulcer. In aspirin induced ulcer model the extract showed ulcer inhibition 48.64% and 64.00% in CCLD and CCHD respectively whereas the standard drug ranitidine exhibited 84.64% ulcer inhibition. In stress induced ulcer model CCLD, CCHD and ranitidine exhibited 48.64%, 64.00% and 84.64% ulcer inhibition respectively. In all the models ethanolic extract of Corchorus capsularis seeds has shown significant anti-ulcer activity in dose dependent manner.

Roles of Human Liver Cytochrome P450 Enzymes in Tenatoprazole Metabolism.

Tenatoprazole, a newly developed proton pump inhibitor candidate, was developed as an acid inhibitor for gastric acid hypersecretion disorders such as gastric ulcer and reflux esophagitis. It is known that tenatoprazole is metabolized to three major metabolites of 5'-hydroxy tenatoprazole, tenatoprazole sulfide, and tenatoprazole sulfone in human liver, primarily catalyzed by CYPs 2C19 and 3A4. While CYP2C19 prefers the hydroxylation of tenatoprazole at C-5' position, CYP3A4 is mainly involved in sulfoxidation reaction to make tenatoprazole sulfone. Tenatoprazole sulfide is a major human metabolite of tenatoprazole and is formed spontaneously and non-enzymatically from tenatoprazole. However, its metabolic fate in the human liver is not fully known. Furthermore, no systematic metabolic study has been performed to study tenatoprazole or tenatoprazole sulfide. Here, we studied the functions of human cytochromes P450 in the metabolic pathway of tenatoprazole and tenatoprazole sulfide by using recombinant human P450s and human liver microsomes. Both CYP 2C19 and CYP3A4 showed distinct regioselective and stereospecific monooxygenation activities toward tenatoprazole and tenatoprazole sulfide. Furthermore, a new major metabolite of tenatoprazole sulfide was found, 1'-N-oxy-5'-hydroxytenatoprzole sulfide, which has never been reported. In conclusion, the metabolic fates of tenatoprazole and tenatoprazole sulfide should be considered in the clinical use of tenatoprazole.

Painting a Complete Picture of the Pathogenesis of Peptic Ulcers

Peptic ulcers, including duodenal and gastric ulcers, were currently considered an infectious disease caused by Helicobacter pylori. However, this etiology cannot explain the major characteristics and observations/phenomena of the disease. To address the challenge, a Complex Causal Relationship with its accompanying methodologies was applied to analyze the existing data. Peptic ulcers were identified as a psychosomatic disease triggered by psychological stress, whereas Helicobacter pylori plays a secondary role in the late phase of peptic ulceration. This etiology addresses all the characteristics, observations/phenomena, controversies, and mysteries of peptic ulcers in a series of 6 articles. This third article discusses the etiology in-depth, painting a complete picture of the pathogenesis of peptic ulcers. The early phase is a long-term abstract psychopathological process, starting from early life when the impacts of multiple psychosomatic factors are transformed into hyperplasia and hypertrophy of gastrin and parietal cells and/or negative life-views via superposition mechanism. These pre-existing abnormalities potentiate the individual’s response to current psychological stress in the intermediate phase, resulting in hypersecretion of gastric acid and/or pre-ulcer lesions. The late phase is a corrosion process caused by gastric acid, Helicobacter pylori, and/or NSAIDs, resulting in duodenal and/or gastric ulcers. This complete picture highlights the importance of past life experience in peptic ulcers and visualizes the non-causal roles of gastric acid, Helicobacter pylori, and NSAIDs. Significantly, the holistic view provided by the complete picture suggests that life phenomena and diseases are highly complex, and an advanced way of thinking is indispensable for life science and medical studies.

S2290 Complete Esophageal Obstruction: A Rare Complication of Zollinger-Ellison Syndrome (ZES)

Introduction: Patients diagnosed with ZES typically have minimal esophageal morbidity given advancements in anti-secretory medications. This case presents a rarely documented sequala of modern-day patients with ZES. Case Description/Methods: A 73-year-old man with history of HIV on HAART and ZES presented with worsening dysphagia to both solids and liquids. In the 2 year interval since his original presentation, his medical therapy was quickly maximized to omeprazole 180 mg/day and famotidine 80 mg/day. He also underwent tumor resection with distal gastrectomy, resection of D1, roux-en-Y hepaticojejunostomy, and truncal vagotomy. During that time his gastrin levels normalized from 1941 to 87. Despite these measures, he had undergone 21 EGDs and 7 esophageal stents for dysphagia secondary to refractory esophageal strictures. He lost 48 lbs over 2 years despite extensive attempts at both enteral and total parental nutrition. In January 2022, he presented with inability to swallow his own secretions and profound weakness from malnutrition. An esophagram was performed (figure 1a) revealing complete esophageal obstruction. An EGD with esophageal lumen restoration was attempted using combined retrograde and anterograde recanalization with 2 operators, 2 EGD scopes, and an EUS needle (figure 1c). Unfortunately, the 2 blind loops appeared to be approximately 6 cm apart in different alignments making lumen restoration unfeasible. The patient was most recently evaluated for esophageal reconstruction by jejunal interposition but was not a candidate due to poor nutritional status. Discussion: ZES is characterized by severe ulcerative disease due to gastric acid hypersecretion via neuroendocrine tumors. Our case is unique because this patient developed complete esophageal obstruction (CEO) despite management with maximal acid suppressive therapy, surgical resection, multiple EGDs with dilations, and numerous esophageal stents. CEO is a rare occurrence characterized by lumen obliteration leading to the inability to tolerate own secretions and most recorded cases are due to radiation-therapy for treatment of head and neck cancers. Given the low incidence, there is no single established method for endoscopic lumen restoration. However recombined retrograde and anterograde recanalization and dilation (CARD) has been shown to be successful for strictures less than 3 cm.Figure 1.: (A) Barium swallow study revealing a high-grade stricture in mid thoracic esophagus followed by another high-grade stricture with complete lumen obstruction. (B) EGD showing blind pouch approximately 35 cm from incisors. (C) Fluoroscopic imaging displaying attempt at combined anterograde and retrograde decannulation and dilation.

Evidence for Metabolic Activation of Omeprazole In Vitro and In Vivo.

Omeprazole (OPZ) is a proton pump inhibitor commonly used for the treatment of gastric acid hypersecretion. Studies have revealed that use of OPZ can induce hepatotoxicity, but the mechanisms by which it induces liver injury are unclear. This study aimed to identify reactive metabolites of OPZ, determine the pathways of the metabolic activation, and define the correlation of the bioactivation with OPZ cytotoxicity. Quinone imine-derived glutathione (GSH), N-acetylcysteine (NAC), and cysteine (Cys) conjugates were detected in OPZ-fortified rat and human liver microsomal incubations captured with GSH, NAC, or Cys. The same GSH conjugates were detected in bile of rats and cultured liver primary cells after exposure to OPZ. Similarly, the same NAC conjugates were detected in urine of OPZ-treated rats. The resulting quinone imine was found to react with Cys residues of hepatic protein. CYP3A4 dominated the metabolic activation of OPZ. Exposure to OPZ resulted in decreased cell survival in cultured primary hepatocytes. Pretreatment with ketoconazole attenuated the susceptibility of hepatocytes to the cytotoxicity of OPZ.

The Hyperplasia and Hypertrophy of Gastrin and Parietal Cells Induced by Chronic Stress Explain the Pathogenesis of Duodenal Ulcers

Peptic ulcers, including duodenal and gastric ulcers, are currently studied as an infectious disease caused by Helicobacter pylori. However, this etiology cannot elucidate the major characteristics and observations/phenomena of the disease, as well as the roles of gastric acid and NSAIDs. Additionally, many patients with severe ulcer symptoms have no infection, suggesting bacterial eradication cannot prevent relapses in all ulcer patients. To address these challenges, a recently published Complex Causal Relationship with its accompanying methodologies was applied to analyze the existing data. Peptic ulcers were identified as a psychosomatic disease triggered by psychological stress, where Helicobacter pylori plays a secondary role in only the late phase of ulceration. An integration of five major etiological theories in history illustrated the entire pathogenesis of peptic ulcers, which addressed all the characteristics, observations/phenomena, controversies, and mysteries of the disease in a series of 6 articles. This first article focuses on the pathogenesis of duodenal ulcers. The hyperplasia and hypertrophy of gastrin and parietal cells induced by chronic stress potentiate the individual’s response to immediate stress, resulting in the hypersecretion of gastric acid and eventually, duodenal ulceration. This psychopathological mechanism resolved all the controversies associated with Helicobacter pylori and explicitly elucidated 7 characteristics of duodenal ulcers, as well as 42 observations/phenomena. The roles of gastric acid, Helicobacter pylori, and NSAIDs in duodenal ulcers were also identified. The effectiveness validated the etiology of duodenal ulcers identified by the Complex Causal Relationship, indicating stress management is essential for a complete cure of the disease without relapse.

LUKOIL lets contracts for Perm refinery's proposed FCC complex

Pancreatic neuroendocrine tumors (PNETs) were formerly termed pancreatic islet tumors. These are rare tumors, comprising 2%–3% of all pancreatic tumors. They derive from pluripotent pancreatic stem cells. PNETs can be classified as functional and nonfunctional. Functional tumors secrete hormones that result in a specific clinical presentation. Insulinomas are the most common PNETs. They are usually benign. Glucagonomas and VIPoma are most commonly malignant. Surgical resection, surgical debulking ± systemic treatment may be used. The Zollinger-Ellison syndrome (ZES) is characterized by gastric acid hypersecretion leading to severe acid-related peptic ulcer disease with diarrhea, caused by a gastrinoma, also a neuroendocrine tumor. The gastrinoma triangle (sweep of duodenum/head of pancreas) is the location of 80% of these tumors. The majority of gastrinomas are located in the duodenum. Gastrinomas may be associated with MEN1 (hyperparathyroidism, pituitary tumors, and gastrinoma) in 20% of cases. Surgical resection is the primary treatment of choice for sporadic gastrinoma. Enucleation of small pancreatic tumors, duodenotomy, and enucleation of small duodenal tumors are the most common procedures performed. Liver resection, hepatic artery embolization and/or chemoembolization, microsphere embolization, radiofrequency or cryoablation, and liver transplantation all have been utilized for metastatic disease.

Antihistaminergic and Anticholinergic Properties of the Root Bark Aqueous Extract of Diospyros mespiliformis (Ebenaceae) on Hypersecretion of Gastric Acid Induced in Wistar Rats.

Objective The objective of this study was to elucidate the antisecretory mechanism of the root bark aqueous extract of Diospyros mespiliformis (RBAEDM) in Wistar rats. Materials and methods. RBAEDM was tested on three experimental animal models of gastric acid hypersecretion including pyloric ligation (PL), PL with histamine, and carbachol pretreatments. The ulcerated surface, mucus mass, pH, gastric acidity, and pepsin activity were determined. Some bioactive compounds revealed by qualitative phytochemistry were quantified. Some markers of oxidative stress in vivo such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and in vitro antioxidant tests (ABTS: 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid, DPPH: 2,2-diphenyl-2-picrylhydrazyl, and FRAP: ferric reducing antioxidant power) were determined. Results In the three models studied, RBAEDM resulted in increases in the percentages of inhibition ranging from 9.50 to 59.52% of gastric ulcer and mucus mass. This increase was accompanied by the reduction in acidity and pepsin activity. The administration of RBAEDM resulted in a significant decrease (p < 0.05, p < 0.01) in MDA levels correlated with a significant increase (p < 0.05, p < 0.01) in CAT and nitrite levels compared with the negative control. RBAEDM has the ability to scavenge ABTS and DPPH radicals and to reduce FRAP, and the inhibitory concentration of 50% (IC50) of the ABTS radical was 220 μg/mL compared with the butylhydroxytoluene (BHT) control (175 μg/mL). Quantitative phytochemistry revealed abundant polyphenols, flavonoids, tannins, saponins, and anthocyanin. Conclusion RBAEDM protected gastric mucous membrane for gastric acid by mechanisms that would involve both anticholinergic and antihistaminergic pathways.

Efficacy of acotiamide on postprandial distress syndrome and epigastric pain syndrome depending on the estimated gastric acid secretion level.

Background/AimsGastric acid secretion is suspected to be a pivotal contributor to the pathogenesis of functional dyspepsia. The present study investigates the potential association of the gastric acid secretion estimated by measuring serum pepsinogen with therapeutic responsiveness to the prokinetic drug acotiamide.MethodsDyspeptic patients consulting participating clinics from October 2017 to March 2019 were prospectively enrolled in the study. The dyspeptic symptoms were classified into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Gastric acid secretion levels were estimated by the Helicobacter pylori infection status and serum pepsinogen using established criteria and classified into hypo-, normo-, and hyper-secretion. Each patient was then administered 100 mg acotiamide thrice daily for 4 weeks, and the response rate to the treatment was evaluated using the overall treatment efficacy scale.ResultsOf the 86 enrolled patients, 56 (65.1%) and 26 (30.2%) were classified into PDS and EPS, respectively. The estimated gastric acid secretion was not significantly different between PDS and EPS. The response rates were 66.0% for PDS and 73.1% for EPS, showing no significant difference. While the response rates were stable, ranging from 61.0% to 75.0% regardless of the estimated gastric acid secretion level among subjects with PDF, the rates were significantly lower in hyper-secretors than in non-hyper-secretors among subjects with EPS (42.0% vs 83.0%, P = 0.046).ConclusionAlthough acotiamide is effective for treating EPS as well as PDS overall, the efficacy is somewhat limited in EPS with gastric acid hyper-secretion, with gastric acid suppressants, such as proton pump inhibitors, being more suitable.

Preliminary Study of Gastroprotective Effect of Aloe perryi and Date Palm Extracts on Pyloric Ligation-Induced Gastric Ulcer in Experimental Rats.

Objective The present study was aimed at investigating the possible antiulcer activities of some natural phytochemicals Aloe perryi leaf extract (APLE) and flower extract (APFE) in addition to the date palm seed extract (DPSE) and the oily samples of DPSE in a pylorus ligation-induced ulcer model using ranitidine as a standard antiulcer drug. Background Peptic ulcer is a prevalent gastrointestinal disorder due to hypersecretion of gastric acid. It affects four million people worldwide, and 2-10% of these ulcers are perforated and cause bleeding. This increases the risk of morbidity and mortality. So we aimed to introduce a primary study alternatively safe method for treating peptic ulcer. Materials and Methods Forty-two Wistar Albino rats of either sex were randomly divided into seven groups (6/each). The pylorus ligation was done to induce ulcer in pretreated albino rats. The antiulcer activities of extracts were estimated at different dose levels (250 and 500 mg/kg) using ranitidine as a standard drug (50 mg/kg). Gastric volume, pH, and total and free acidity as well as ulcer index and percentage of ulcer inhibition were measured to elucidate the antiulcerogenic effects. Histological examination of gastric ulcer was also performed. Statistical analysis for the results was done where P < 0.05 was considered statistically significant. Results Pylorus ligation for 6 h in control rats resulted in gastric ulcer which was indicated by the accumulation of gastric secretion and increased total acidity and decreased pH. The pretreatment of rats with APLE, APFE, and DPSE in addition to the oily samples of DPSE significantly inhibited the ulcers induced by pylorus ligation. These effects were attributed to significant reductions in total and free acidity, ulcer index, and gastric volume while there is a marked decrease in gastric pH (the antisecretory) as well as mucosal strengthening properties of these phytochemicals. Conclusion These findings give these extracts the potential to be a promising tool for the management of gastric ulcer after performing further clinical and experimental studies. Our study demonstrated the promising antiulcer activity of extracts and oils in pyloric ligation-induced gastric ulcer. To the best of our knowledge, this is the first study to explore the antiulcer activity of these extracts; however, further investigations may be recommended for full details about this antiulcerogenic capacity.

Serum gastrin-17 concentration for prediction of upper gastrointestinal tract bleeding risk among peptic ulcer patients.

BACKGROUNDSerum gastrin-17 (G-17), pepsinogen I (PGI), and pepsinogen II (PGII) concentrations regulate gastric acid secretion, and hypersecretion of gastric acid increases the risks of peptic ulcer and upper gastrointestinal bleeding. These associations suggest that serum G-17, PGI, and (or) PGII may predict gastrointestinal bleeding risk among peptic ulcer patients. AIMTo evaluate the efficacies of serum G-17, PGI, PGII, and PGI/PGII ratio (PGR) for predicting upper gastrointestinal bleeding among peptic ulcer patients.METHODSA total of 199 patients diagnosed with peptic ulcer confirmed by gastroscopy and positivity for Helicobacter pylori by the 14C-urea breath test were recruited, including 107 patients with simple peptic ulcer and 92 cases complicated by upper gastrointestinal bleeding. Serum PGI, PGII, G-17, and PGR were measured by immune methods and compared between bleeding and non-bleeding groups by univariate analysis. The specificity and sensitivity of PGs and G-17 for evaluating upper gastrointestinal bleeding risk were then assessed by constructing receiver operating characteristic (ROC) curves.RESULTSSerum G-17 was significantly higher among peptic ulcer patients with upper gastrointestinal bleeding compared to simple peptic ulcer patients (25.34 ± 14.29 vs 8.84 ± 8.03 pmol/L, t = 9.822, P < 0.01), whereas serum PGI, PGII, and PGR did not differ significantly between bleeding and non-bleeding groups (all P > 0.05). The risk of bleeding was significantly higher among peptic ulcer patients with elevated serum G-17 (> 15 pmol/L) compared to patients with normal or low serum G-17 (73.2% vs 27.4%, χ2 = 40.72, P < 0.01). The area under the ROC curve for serum G-17 was 0.866 ± 0.024, and a cut-off of 9.86 pmol/L yielded 90.2% sensitivity and 68.2% specificity for distinguishing peptic ulcer with and without upper gastrointestinal bleeding.CONCLUSIONSerum G-17 is significantly upregulated in peptic ulcer patients and higher levels are predictive of upper gastrointestinal bleeding. Conversely, serum PGI, PGII, and PGR have no predictive value. Further prospective studies are warranted to examine if high G-17 can be used to assess risk of bleeding prior to onset.

S2556 A Case of Pancreatic Gastrinoma Diagnosed by Endoscopic Ultrasound

Introduction: Gastrinomas are a rare neuroendocrine tumor that predominantly secretes gastrin and leads to peptic ulcer disease, acid reflux, and malabsorption. Diagnosis is usually made by gastrin levels and secretin stimulation test (SST). Here, we present a case of gastrinoma diagnosed by endoscopic ultrasound (EUS). Case Description/Methods: 49 year old female with chronic pancreatitis secondary to alcohol presented for syncopal episode. She noted melena for the last 4 days, with a similar episode 2 years ago found to have “bad stomach ulcers”, but with no follow-up. She was transfused blood and started on PPI upon arrival. Upper endoscopy showed thickened gastric folds and extensive ulceration from duodenum to jejunum suggestive of gastric acid hypersecretion. Further work up showed gastrin 436 and gastric acid pH 1-2. Due to concern for outpatient follow-up, octreotide scan was done which was negative. We proceeded to EUS with the patient’s consent, which showed atrophic pancreas with calcification throughout, and a 2-3 cm focal parenchyma devoid of calcification suspicious for mass from which fine needle aspiration (FNA) was performed. Pathology confirmed a well-differentiated neuroendocrine tumor. Patient was continued on PPI and referred outpatient for surgical resection. Discussion: The screening criteria of gastrinoma is fasting gastrin level > 1000 pg/mL and gastric pH < 2. SST can confirm diagnosis for those without active severe manifestations due to risks of stopping PPI in these patients. For localization, Ga-68 dotatate PET CT is the most sensitive test while octreotide scan has lower sensitivity and specificity. If these are unsuccessful, EUS and exploratory laparotomy may be considered. In this case, our patient was difficult to diagnose. Her clinical and endoscopic findings were highly suggestive of gastrinoma, however her initial tests were inconclusive and an SST was unable to be performed due to her acute presentation. With our endoscopy team, a suggestive pancreatic lesion was biopsied and confirmed the diagnosis. EUS is a relatively low risk procedure that allows for FNA as an alternative to diagnose gastrinomas. Studies have found that EUS has high sensitivity for detection and localization, particularly for pancreatic tumors, and can detect even small tumors. Therefore, EUS can be an effective and safe method to diagnosis that can lead to definitive treatment.Figure 1.: (a) Numerous large, circumferential duodenal ulcers on EGD. (b) Ulcer extension to the jejunum on EGD. (c) Atrophic calcified pancreas with focal area devoid of calcifications between pancreatic neck and body on EUS. (d) H&E showing polygonal cells with round, regular nuclei. (e) Synaptophysin positivity for neuroendocrine differentiation supporting gastinoma.

Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies.

Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.

How did the ancient bacterium, Helicobacter pylori, cause an epidemic of chronic duodenal ulceration?

The association of Helicobacter pylori with chronic duodenal ulceration was a seminal observation in the short history of gastroenterology. However, H. pylori is now known to be an ancient bacterium, whereas there is persuasive evidence that the epidemic of duodenal ulceration began in the second half of the 19th century and continued into the second half of the 20th century. Possible explanations for the epidemic include genomic changes in the organism and environmental or other influences on the human host. While genomic changes resulted in the appearance of virulence factors, these seem likely to have appeared thousands of years ago with minimal effects on gastritis because of coexisting suppression of gastric immunity. In contrast, the emergence of duodenal ulceration is best explained by a change in the pattern of gastritis from inflammation involving the antrum and body in most individuals to a significant minority (10–20%) with antral gastritis but with relative sparing of the body of the stomach. In the latter group, the increase in serum gastrin (particularly G17) associated with antral gastritis had trophic effects on gastric parietal cells with an increase in the parietal cell mass and hypersecretion of gastric acid. Hypersecretion of acid is seen as the major risk factor for duodenal ulceration with significant contributions from environmental factors including smoking and use of nonsteroidal, anti‐inflammatory drugs. Host factors favoring changes in the pattern of gastritis include delayed acquisition of infection and improved nutrition; both with enhancing effects on mucosal immunity.

Total gastrectomy for severe proton pump inhibitor-induced hypomagnesemia in a MEN1/Zollinger Ellison syndrome patient

We report here the first case of life-threatening hypomagnesemia in a Zollinger-Ellison syndrome patient with multiple endocrine neoplasia type 1 (MEN1) syndrome. The severe symptomatic hypomagnesemia proved to be due to proton pump inhibitors (PPIs), but withdrawal of PPIs led to early severe peptic complications despite a substitution by histamine H2-receptor antagonist therapy. Simultaneous management of life-threatening hypomagnesemia, severe gastric acid hypersecretion and MEN1-associated gastrinomas was complex. A total gastrectomy was performed in order to definitely preclude the use of PPIs in this frail patient who was not eligible for curative pancreatoduodenal resection.

Physiology of the distal convoluted tubule and collecting duct

Antacids are usually alkaline substances that are used to neutralise excess acid in the stomach. Antacids were developed based on the hydroxides and carbonates of the group II and III metals, as well as the bicarbonates of the alkali metals. Antacids can be classified into two main classes being non-absorbable or absorbable antacids. Non-absorbable antacids have fewer side effects and further advantageous properties. Each antacid has a specific active ingredient which has a different effect on the gastric acid. Antacids act similar to when an acid reacts with a hydroxide; a salt and water are produced. Antacids are more effective in the form of suspension. The average therapeutic dose of an antacid is 10–15 ml of liquid or one to two tablets three to four times a day. These drugs have small volumes of distribution, undergo minimal hepatic metabolism and are excreted in faeces. Antacids that contain calcium, magnesium and aluminium ions are chelators. To avoid undesirable interactions, antacids are usually used two hours before or after taking any medication. Stress ulcerations are common in intensive care unit (ICU) patients. The pathophysiology of the ulceration probably results from an imbalance between mucosal protection and gastric acid hypersecretion. Whilst prophylaxis was provided to every patient previously, it is wise to individualise the decision and to only provide it to high risk patients. For critically ill patients who are able to receive enteral medications and in whom prophylaxis is indicated, an oral proton pump inhibitor (PPI) is preferred rather than an alternative prophylactic agent. For critically ill patients who cannot receive enteral medications, an intravenous (IV) histamine 2 (H2) receptor blocker or IV PPI can be administered. Where PPIs or H2 blockers cannot be administered, sucralfate is a suitable oral alternative.