Zollinger-Ellison Research Articles

Formulation development and evaluation of omeprazole buccal tablets

Omeprazole is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome. It is also used to prevent upper gastrointestinal bleeding in people who are at high risk. The Mucoadhesive buccal tablets were prepared by direct compression method using Sodium Alginate, HPMC K4M and SCMC as mucoadhesive polymer. The compatibility studies of drug and excipients were performed by FT-IR spectroscopy. After examining the flow properties of the powder blends the results are found to be within prescribed limits and indicated good flowing property, hence it was subjected to tablet compression. The tablets were evaluated for post compression parameters like weight variation, hardness, thickness, friability, drug content uniformity, Surface pH, in-vitro studies like drug release. Formulation (F4) containing HPMC K4M in the ratio of (1:1) showed maximum drug release of 99.54% in 8 hrs. The drug content of shown highest of 99.61 %, Surface pH was found to be 6.05. All the evaluation parameters given the positive results and comply with the standards. The results indicate that the mucoadhesive buccal tablets of Omeprazole may be good choice to bypass the extensive hepatic first pass metabolism with an improvement in the bioavailability of Omeprazole through buccal mucosa.

All you need to know about gastrinoma today | Gastrinoma and Zollinger-Ellison syndrome: A thorough update.

Zollinger-Ellison syndrome (ZES) is a distinct syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea. It is the result of a gastrin-excess state caused by a duodenal or pancreatic neuroendocrine tumor referred to as gastrinoma. This gastrin-secreting neuroendocrine tumor is usually sporadic in nature, or part of multiple endocrine neoplasia type 1 syndrome. The high rate of malignancy associated with gastrinomas substantiates the need for early diagnosis. In order to diagnose ZES with laboratory tests, patients under antacid medication are required to stay off proton pump inhibitors for at least one week and H2 receptor antagonists for 48 h. Fasting serum gastrin level measurement serves as an initial and fundamental diagnostic test, boasting a sensitivity of 99%. Gastrinoma patients will present with a gastrin level greater than 100 pg/mL, while a serum gastrin level higher than 1000 pg/mL, in the presence of gastric pH <2, is considered diagnostic. Since more common causes of hypergastrinemia exist in the setting of hypochlorhydria, ruling those out should precede ZES consideration. Such causes include atrophic gastritis, Helicobacter pylori (H. pylori)-associated pangastritis, renal failure, vagotomy, gastric outlet obstruction and retained antrum syndrome. The secretin stimulation test and the calcium gluconate injection test represent classic adjuvant diagnostic techniques, while alternative approaches are currently being introduced and evaluated. Specifically, the secretin stimulation test aids in differentiating ZES cases from other hypergastrinemic states. Its principle is based on secretin stimulation of gastrinoma cells to secrete gastrin, while inhibiting normal G cells. The rapid intravenous infusion of 4 μg/kg secretin over 1 min is followed by gastrin level evaluation at specific intervals post-infusion. Localization of the primary tumor and its metastases is the next diagnostic step when gastrinoma-associated ZES is either suspected or biochemically confirmed. Endoscopic ultrasound has showcased sensitivity as high as 83% for pancreatic gastrinomas and is considered the primary modality in such cases, although its tumor detection rates are substantially lower in duodenal lesions. Gallium-68 radiotracers, especially DOTATOC with positron emission tomography, are currently setting the standard in tumor localization, enhancing traditional imaging techniques and showcasing high sensitivity and specificity. Although gastrinomas have been reported in various anatomic locations, the vast majority arise in a specific site named the "gastrinoma triangle", involving parts of the duodenum, pancreas and extra-hepatic biliary system. Proton pump inhibitors serve as the cornerstone of symptomatic ZES treatment. Surgery is routinely performed in localized sporadic ZES, irrespective of imaging results. ZES in multiple endocrine neoplasia type 1 requires work-up for evaluation and treatment of hyperparathyroidism, while surgery might be an option for selected cases. In cases of advanced and metastatic disease, there is a variety of potential treatments, ranging for somatostatin analogs to chemotherapeutic drugs, liver-directed therapies and liver transplantation, while neither hepatic metastases, nor locally invasive disease necessarily preclude surgical management. This article thoroughly and critically reviews available literature and provides an extensive and multidimensional overview of ZES, along with current controversies regarding management of this disease.

Successful Lifetime/Long-Term Medical Treatment of Acid Hypersecretion in Zollinger-Ellison Syndrome (ZES): Myth or Fact? Insights from an Analysis of Results of NIH Long-Term Prospective Studies of ZES.

Analysis of the efficacy/pharmacology of long-term/lifetime medical treatment of acid hypersecretion in a large cohort of ZES patients in a prospective study. This study includes the results from all 303 patients with established ZES who were prospectively followed and received acid antisecretory treatment with either H2Rs or PPIs, with antisecretory doses individually titrated by the results of regular gastric acid testing. The study includes patients treated for short-term periods (<5 yrs), patients treated long-term (>5 yrs), and patients with lifetime treatment (30%) followed for up to 48 years (mean 14 yrs). Long-term/lifelong acid antisecretory treatment with H2Rs/PPIs can be successfully carried out in all patients with both uncomplicated and complicated ZES (i.e., with MEN1/ZES, previous Billroth 2, severe GERD). This is only possible if drug doses are individually set by assessing acid secretory control to establish proven criteria, with regular reassessments and readjustments. Frequent dose changes both upward and downward are needed, as well as regulation of the dosing frequency, and there is a primary reliance on the use of PPIs. Prognostic factors predicting patients with PPI dose changes are identified, which need to be studied prospectively to develop a useful predictive algorithm that could be clinically useful for tailored long-term/lifetime therapy in these patients.

Рабепразол в лечении кислотозависимых заболеваний

Proton-pump inhibitors (PPIs) are widely used to treat acid-related disorders (ARD). Rabeprazole is a potent inhibitor of gastric H+/K+-ATPase, and it is indicated for the treatment of gastroesophageal reflux disease, Zollinger-Ellison syndrome, gastric and duodenal ulcers and for Helicobacter pylori eradication (in combination with antibiotics), as well as for the treatment of ARD described in this article. Pharmacokinetic and pharmacodynamic data show that rabeprazole provides a marked acid inhibition from the first administration, which persists with repeated use. Due to the predominantly non-enzymatic metabolism, rabeprazole has a lower interaction potential between drugs. Besides, rabeprazole maintains a high intragastric pH and achieves maximum acid inhibition in 24 hours. Rabeprazole is characterized by linearity of pharmacokinetics, which remains unchanged in renal and hepatic insufficiency. Rabeprazole is available in the dosage form of enteric capsules due to the PPIs instability in an acidic environment. Rabeprazole is generally well-tolerated by patients. Besides several minor side effects, rabeprazole is safe to be widely used in the treatment of ARD. KEYWORDS: proton pump inhibitors, antisecretory drugs, rabeprazole, efficacy, safety, expediency, acid-related disorders, gastroesophageal reflux disease, peptic ulcer, gastropathy, dyspepsia. FOR CITATION: Tsukanov V.V. Rabeprazole in the treatment of acid-related disorders. Russian Medical Inquiry. 2023;7(5):264–273 (in Russ.). DOI: 10.32364/2587-6821-2023-7-5-4.

Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors.

Proton Pump Inhibitors are used widely to manage many gastric acid-related conditions such as gastroesophageal disease, gastritis, esophagitis, Barrett's esophagus, Zollinger-Ellison syndrome, peptic ulcer disease, nonsteroidal anti-inflammatory drug-associated ulcers, and Helicobacter pylori eradication, around the globe. This review article focuses on adverse effects associated with the long-term use of proton pump inhibitors. Various observational studies, clinical trials, and meta-analyses have established the adverse effects associated with the long-term use of proton pump inhibitors including renal disorders (acute interstitial nephritis, acute kidney injury, chronic kidney disease, and end-stage renal disease), cardiovascular risks (major adverse cardiovascular events, myocardial infarction, stent thrombosis, and stroke), fractures, infections (Clostridium difficile infection, community-acquired pneumonia, and Coronavirus disease 2019), micronutrient deficiencies (hypomagnesemia, anemia, vitamin B12 deficiency, hypocalcemia, hypokalemia), hypergastrinemia, cancers (gastric cancer, pancreatic cancer, colorectal cancer, hepatic cancer), hepatic encephalopathy, and dementia. Clinicians including prescribers and pharmacists should be aware of the adverse effects of taking proton pump inhibitors for an extended period of time. In addition, the patients taking proton pump inhibitors for long-term should be monitored for the listed adverse effects. The American Gastroenterological association recommends a few non-pharmacological measures and the use of histamine 2 blockers to lessen gastrointestinal symptoms of gastroesophageal reflex disease and the utilization of proton pump inhibitors treatment if there is a definitive indication. Additionally, the American Gastroenterological association's Best Practice Advice statements emphasize deprescribing when there is no clear indication for proton pump inhibitors therapy.

Formulation Development and Evaluation of Oro-Dispersible Tablets Based On Solid Dispersion of Cimetidine

The most common problem about conventional dosage form is dysphagia (difficulty in swallowing). So, we design a new approach in a conventional dosage form which is oral dispersible tablet. Oral dispersible tablet is also called as mouth dissolving tablet, fast dissolving tablet, or oral disintegrating tablet. Oral dispersible tablet has advantage as it quickly disintegrates into saliva when it is put on the tongue. The faster the drug disintegrates or is dissolved, the faster the absorption and the quicker the therapeutic effect of drug will be attained. The objective of present study was to formulate directly compressible orodispersible tablets of cimetidine with improved solubility and bioavailability by using solid dispersion technique. Cimetidine is a histamine H2-receptor antagonist. It is widely prescribed in active duodenal ulcers, gastric ulcers, Zollinger-Ellison syndrome, gastroesophageal reflux disease and erosive esophagitis. Solid dispersion of cimetidine was prepared by anti-solvent addition method and physical mixture using novel polymer eudragit E 100. Saturation solubility of drug was determined in physical mixture and solid dispersion formulation. The prepared solid dispersion formulations were further characterized by drug contents, HPLC, and encapsulation efficiency. Orodispersible tablets of cimetidine were prepared by direct compression method and blend was evaluated for the pre-compression parameters such as bulk density, compressibility, angle of repose etc. The tablets were prepared by using selected solid dispersion formulation and excipients with sodium starch glycolate as a superdisintegrant and evaluated for hardness, friability, weight variation, content uniformity, wetting time, dispersion time and in-vitro drug release. Orodispersible tablet shows wetting time 27±1 seconds and in-vitro drug release 93.20±3.181%, which is better as compare to tablet containing pure drug (82.36±1.986) within 20min. Thus formulation of orodispersible tablet of cimetidine solid dispersion showed increased solubility and bioavailability with patient complies and convenience.&#x0D; Keywords: Cimetidine, Orodispersible tablets, Solid dispersion, Anti solvent addition method, Superdisintegrant

Clinical and Surgical Management of Zollinger-Ellison Syndrome: A Literature Review

Zollinger-Ellison Syndrome is a rare disease caused by tumors called "Gastrinomas", causing high levels of gastrin that produces acid hypersecretion and even gastric ulcers. We present a 20-year-old patient with a 2-month history of pain in the epigastrium accompanied by nausea, vomiting, and weight loss with a history of upper gastrointestinal bleeding from a duodenal ulcer, which on physical examination revealed a tumor in the epigastrium. Contrast-enhanced abdominal CT showed a tumor mass in the tail of the pancreas. She underwent surgery, performing a corporocaudal pancreatectomy and splenectomy, with favorable post-surgical evolution. The anatomopathological study reports pancreatic gastrinoma.

Clinical and Surgical Management of Zollinger-Ellison Syndrome: A Literature Review

Clinical and Surgical Management of Zollinger-Ellison Syndrome: A Literature Review

Sporadic and MEN1-related gastrinoma and Zollinger–Ellison syndrome: differences in clinical characteristics and survival outcomes

PurposeGastrinoma with Zollinger–Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features.MethodsConsecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort.ResultsOf 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively.ConclusionMEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.

RF27 | LBSUN361 Understanding The Genetics Of Multiple Endocrine Neoplasia Type 1: The Road Ahead

Abstract Background About 10-30% patients have genotype-negative (GN)-MEN1. Here, we compare our cohort of comprehensively phenotyped GN-MEN1 and genotype-positive (GP)-MEN1 patients. We also investigate somatic mosaicism as a cause of GN-MEN1. Methods GN-MEN1 patients showed no mutations in MEN1 or other primary hyperparathyroidism (PHPT) genes (CASR, RET, CDKN1B, CDC73, AIP, GNA11, AP2S1, GCM2) performed per clinical indication. Index patients (first patient in kindred to be diagnosed with MEN1) or probands (first patient in kindred to be evaluated at our center) from kindreds with GP-MEN1 were identified. All patients underwent testing for tumor biomarkers, imaging and evaluation for Zollinger-Ellison syndrome (ZES). Whole exome sequencing was performed on multiple tumors from 13 GN-MEN1 patients. GP-MEN1 patients were also categorized into high-impact (nonsense, frameshift, splice site, whole or partial gene deletion) or low-impact (missense or in-frame indels) mutation-bearing groups. Results We identified 43 (31 females, 12 males) patients with GN-MEN1 and 160 (102 index, 58 probands) patients with GP-MEN1 (98 females, 62 males). Among GP-MEN1, 97 had high impact and 34 had low-impact mutations. Mean age at last follow-up was 56 (±14) years for GN-MEN1 and 52 (±16) years for GP-MEN1 patients. Among the GN-MEN1 patients, 38/42 developed PHPT - 3/38 (8%) had recurrent disease. In GP-MEN1, 144/149 developed PHPT - 83/144 (58%) with recurrent disease. Median age of index presentation with PHPT significantly differed between the groups (27.5 years in GP-MEN1 vs 53 years in GN-MEN1 (χ2 (1)=5.5: p &amp;lt;0.05)). 33/42 GN-MEN1 patients had a pituitary adenoma (22/33 functioning - 9/22 prolactinomas; 8/22 GH-secreting). In comparison, 94/145 GP-MEN1 patients developed a pituitary adenoma (51 functioning - 37/51 prolactinomas, no GH-secreting tumors). In the GN-MEN1 group, 12/42 (29%) patients developed a gastro-entero-pancreatic (GEP)-NET. In comparison, 86/130 (66%) patients with GP-MEN1 had a GEP-NET. Somatic variants in MEN1, CDC73 or CDKI were observed in six tumors. However, these mutations were not seen in another tumor/s or germline DNA from the patient. All patients with high-impact mutations had PHPT (63% had recurrent disease), 70% had pituitary tumors (35% with macro-adenomas) and 61% developed GEP-NETs (29% with distant metastases). In comparison, 91% patients with low-impact mutations developed PHPT (41% with recurrent disease), 69% developed pituitary tumors (23% with macro-adenomas) and 65% developed GEP-NETs (35% with distant metastases). Conclusion Patients with GP-MEN1 generally experience younger age of onset, greater likelihood of recurrent PHPT and co-occurrence of GEP-NETs in comparison to GN-MEN1. Our findings do not support somatic mosaicism as a cause of GN-MEN1. No apparent correlation in phenotype between high-impact vs. low-impact mutations is noted. Presentation: Monday, June 13, 2022 12:51 p.m. - 12:56 p.m.

S3363 A Case of Progressive Refractory Diarrhea due to Zollinger-Ellison Syndrome

Introduction: A 64-year-old female with a history of diabetes mellitus presents with acute on chronic diarrhea and refractory acid reflux is found to have Zollinger-Ellison syndrome. Case Description/Methods: The patient had a two-year history of non-bloody diarrhea which worsened (7 bowel movements/day) in the two months prior to presentation. She described associated nausea, reflux, and abdominal pain. Notably, her mother had similar symptoms, requiring small bowel resection (records not available). Previous workup included a colonoscopy and an esophagoduodenoscopy (EGD) showing duodenal ulcerations with negative biopsies for celiac disease. She was started on a proton-pump inhibitor (PPI), colestipol, and loperamide without improvement. Medication review, stool infectious studies, and cross-sectional imaging had been unrevealing. On presentation, she had stable vitals and physical exam significant for diffuse abdominal tenderness. Labs were notable for a hemoglobin of 10.2 gm/dL (grams per deciliter) and an acute kidney injury (AKI). Abdominal Computed Tomography (CT) suggested multiple, small duodenal ulcers with a polypoid lesion in the gastric antrum (Figure). EGD revealed esophagitis, multiple small duodenal ulcerations (D1, D2), and gastric mucosal atrophy. Repeat colonoscopy was unremarkable. The fasting gastrin level was 211 pg/mL (picogram per milliliter). The secretin stimulation test showed serum gastrin blood levels of 121, 258, and 483 pg/mL at 2, 5, and 10 minutes respectively consistent with Zollinger-Ellison Syndrome. The Dotatate PET/CT scan showed metastatic somatostatin receptor expressing portocaval adenopathy without a tracer-avid primary neuroendocrine tumor. She was started on lanreotide and is now referred to oncology. Discussion: This case represents an instructive example of Zollinger Ellison Syndrome (ZES), often discussed, but rarely diagnosed. In this case, the patient presented with progressive diarrhea, a subtle family history, and with several prior evaluations. ZES is a rare gastrin-secreting neuroendocrine tumor (NET) associated with multiple endocrine neoplasia (MEN-1), which leads to refractory acid reflux and chronic diarrhea, as seen in our patient. Non-specific gastrointestinal symptoms and empiric PPI use can delay the diagnosis. The gastric pH, gastric level, secretin stimulation, and Dotatate PET/CT are used to evaluate and localize the tumor.Figure 1.: A, B: Computed Tomography (CT) abdomen showed multiple, small duodenal ulcers and 4 millimeter (mm) enhancing polyp at the gastric antrum (red arrows).

S3640 Myoclonic Jerks and Chronic Diarrhea; The Challenges of Zollinger-Ellison Syndrome

Introduction: Zollinger-Ellison Syndrome (ZES) is a rare disorder caused by hypersecretion of gastrin, causing peptic ulcer disease (PUD) and diarrhea. In most cases, inappropriate gastrin secretion is from duodenal or pancreatic neuroendocrine tumors (gastrinoma). Diagnosis of gastrinoma can be delayed as symptoms are nonspecific and can be misdiagnosed as other GI disorders. Case Description/Methods: A 79yo female with DM, HTN, and peptic ulcer disease presented with myoclonic jerks and watery diarrhea. She was found to have severe hypomagnesemia and acute kidney injury (AKI). Notably she had diarrhea for months with several admissions with similar symptoms. Prior workup including celiac serology, vasoactive intestinal peptide level, fecal calprotectin, and colonoscopy were inconclusive. Lomotil was started for possible irritable bowel syndrome (IBS) with partial response. On this admission, stool osmolar gap was < 50, chromogranin A 8224 ng/mL and gastrin 596 pg/mL. MRI of the abdomen showed a 2.5cm mass-like thickening in the distal gastric antrum. Endoscopy showed gastritis and duodenal ulcers. EUS with FNA of the mass was inconclusive. Octreoscan revealed a somatostatin receptor-bearing neuroendocrine tumor (NET) in the distal stomach. She underwent distal gastrectomy and peri-pancreatic LN resection after hospitalization. Histopathology confirmed a well-differentiated NET with metastasis. Her diarrhea resolved and chromogranin A and gastrin normalized, 90 ng/mL and 43 pg/mL respectively. (Figure) Discussion: Chronic diarrhea is a main symptom of gastrinomas. Diagnosis can be challenging due to the rarity of ZES and as many disorders cause diarrhea. Many patients are diagnosed with more common conditions such as IBS and GERD. Initial evaluation in suspected cases includes Gastrin levels which can be falsely elevated in patients on chronic PPI. Most gastrin-producing tumors arise in the duodenum (75%) and pancreas (20%). Less than 5% of patients have a tumor in the stomach, peri-pancreatic lymph nodes, liver, bile ducts, or ovary. EGD can show prominent gastric folds and pathology can be nonspecific. In patients with suspected ZES, chest and abdominal imaging can identify intra or extra-abdominal lesions. Octreoscan can localize the tumor’s primary location and any metastasis. Consideration of ZES in patients with chronic diarrhea with timely evaluation and treatment can prevent the complications such as electrolyte abnormality, PUD, and decreases risk of metastasis.Figure 1.: a,b. Duodenal Ulcers. Image c. 2.5 cm mass-like thickening with restricted diffusion in the distal gastric antrum suspicious for neoplasm with an adjacent 1.5 cm lymphadenopathy.

S3615 Gastric Neuroendocrine Tumor of Indeterminate Type

Introduction: Gastric neuroendocrine tumors (GNETs) are rare tumors making up less than 2% of gastric polyps. Type I GNETs are most common (70-80%) and are associated with atrophic gastritis, pernicious anemia, iron deficiency, elevated gastrin, and high gastric pH. These are typically small, low-grade, and may be multifocal. Type II tumors are also associated with elevated gastrin levels but a low pH, as seen in Zollinger-Ellison syndrome. Type III tumors are larger and more aggressive and occur sporadically in the setting of normal gastric mucosa, normal gastrin levels, and normal pH. Here we discuss an unusual case of GNET which does not fit into either category. Case Description/Methods: A 70-year-old white male with history of gastroesophageal reflux disease (GERD) on chronic proton pump inhibitor (PPI) presented for esophagogastroduodenoscopy (EGD) for worsening GERD symptoms. EGD revealed 2 polyps in the body – each was 4-5 mm and was removed with hot snare. A few smaller polyps were removed with biopsy forceps. The gastric mucosa was grossly normal. Sydney protocol biopsies were obtained. The 2 larger polyps returned as well-differentiated GNETs, grade 1 (Ki-67 index 2.5%). The smaller polyps returned as areas of intestinal metaplasia (IM), but Sydney protocol biopsies did not reveal H. pylori, atrophic gastritis, or IM. EGD was repeated off PPI for 1 week and fasting labs were obtained. Gastric pH was 1, serum gastrin was 78 pg/mL (normal), vitamin B12 and ferritin were normal, and intrinsic factor and parietal cell antibodies were negative. (Figure) Discussion: This case highlights a scenario in which a GNET is difficult to categorize based on classic criteria. As type III lesions are very aggressive with high risk of metastasis, distinguishing between type I and type III lesions is paramount. While grossly and histologically resembling a type I GNET (multifocal, small, low-grade), the GNETs in this case were present in the absence of atrophic gastritis, and the patient had a normal gastrin and low gastric pH off PPI. The lack of atrophic gastritis and normal gastrin levels are more suggestive of a type III tumor, but one would expect a single, large, high-grade GNET in that case. As PPI use has increased in the past 30 years, so has incidence of GNETs; it is possible that a chronic, PPI-induced “hyper-gastrin” state was responsible for this patient’s GNETs and that gastrin normalized once PPI was discontinued. More studies are needed to further categorize GNETs with indeterminate features.Figure 1.: Gastric Polyp.

To deprescribe or not to deprescribe, that is the question

To deprescribe or not to deprescribe, that is the question

Radiological Features of Zollinger-Ellison Syndrome: A Report of Two Cases.

Hypersecretion of gastrin from duodenal or pancreatic gastrinomas results in a rare clinical entity called Zollinger–Ellison syndrome (ZES). It mostly presents with abdominal pain and diarrhea. ZES may be sporadic or occur in association with multiple endocrine neoplasia type 1. Usually, ZES manifests between 20 and 50 years.We report two cases of patients who presented with abdominal pain, vomiting, watery diarrhea, and significant weight loss.

Zollinger-Ellison Syndrome - review

Introduction and purpose&#x0D; Zollinger-Ellison syndrome (ZES) is a constellation of symptoms that includes gastric ulcer, gastroesophageal reflux disease (GERD), and chronic diarrhea. They are caused by the presence of gastrinoma, which is a neuroendocrine tumor that secretes gastrin. Gastrinoma is most often found in the duodenum and pancreas. ZES occurs sporadically in about 80% of cases, while in 20-25% it is a component of multiple endocrine neoplasms (MEN1). It is malignant in 60-90% of cases. The aim of the study is to present the typical clinical course of ZES, the diagnostic path and current therapeutic recommendations.&#x0D; Description of the state of knowledge &#x0D; ZES is present in about 0.1% -1% of patients with peptic ulcer disease. The direct cause of symptoms in patients with ZES is excessive gastric secretion stimulated by ectopic gastrin. Excess gastric acid damages the gastric mucosa and small intestine and disrupts the transport of fats, leading to the development of diarrhea. Other common symptoms include abdominal pain, nausea, or more rarely severe complications of GERD or peptic ulcer disease. Diagnostics include measurement of fasting serum gastrin, measurement of gastric pH, and assessment of basal gastric acid production.&#x0D; Summary &#x0D; In pharmacological treatment, proton pump inhibitors (PPIs) are the first-line drugs to control excessive gastric acid secretion in patients with ZES. Other therapeutic options include histamine receptor antagonists or somatostatin analogues. Surgical intervention remains the only possible causal treatment. In the case of sporadic ZES routine exploratory laparotomy with curative intent is recommended. In the group of patients with coexisting MEN-1 syndrome, surgical intervention is reserved for patients with tumors&gt; 2 cm.

Cross-sectional Imaging of the Duodenum: Spectrum of Disease.

Cross-sectional Imaging of the Duodenum: Spectrum of Disease.

Peptic ulcer: the current state of the problem

Peptic ulcer disease (PUD) is a chronic polyetiological recurrent disease of gastroduodenal region. In most cases, the pathogenesis of PU is caused by imbalance between the aggressive factors and protective factors of the gastric or duodenal mucosa. Helicobacter pylori (H. pylori) infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, are the major causative factors leading to PUD development. 65% of gastric ulcers and 80% of duodenal ulcers were found to be associated with H. pylori infection. In turn, NSAIDs account for 30% of gastric ulcers and 15% of duodenal ulcers. About 0.1–1% of all PUs are caused by Zollinger-Ellison syndrome. Abdominal pain is the leading symptom in the clinical findings of patients with exacerbation of PUD. Dyspeptic syndrome (vomiting, nausea, belching, abnormal bowel pattern) is much less common in patients with PUD. Endoscopic examination of the upper gastrointestinal tract is currently the gold standard test used in the diagnosis of PUD and is recommended for all patients suspected of having this disease (unless contraindicated). Antisecretory therapy including proton pump inhibitors is the main approach to the treatment of PUD, as well as the prevention of its complications. Integral to the treatment of patients with H. pylori-associated PU is the eradication therapy of the infection. It is reasonable to use a cytoprotector rebamipide, which accelerates ulcer healing and improves the resulting scar quality, as part of the pharmacotherapy of PUD. In addition, the use of rebamipide in H. pylori eradication therapy regimens contributes to increased efficiency of elimination of the microorganisms.

Gastric neuroendocrine neoplasms: a primer for radiologists.

Gastric neuroendocrine neoplasms are uncommon tumors with variable differentiation and malignant potential. Three main subtypes are recognized: type 1, related to autoimmune atrophic gastritis; type 2, associated with Zollinger-Ellison and MEN1 syndrome; and type 3, sporadic. Although endoscopy alone is often sufficient for diagnosis and management of small, indolent, multifocal type 1 tumors, imaging is essential for evaluation of larger, high-grade, and type 2 and 3 neoplasms. Hypervascular intraluminal gastric masses are typically seen on CT/MRI, with associated perigastric lymphadenopathy and liver metastases in advanced cases. Somatostatin receptor nuclear imaging (such as Ga-68-DOTATATE PET/CT) may also be used for staging and assessing candidacy for peptide receptor radionuclide therapy. Radiotracer uptake is more likely in well-differentiated, lower-grade tumors, and less likely in poorly differentiated tumors, for which F-18-FDG-PET/CT may have additional value. Understanding disease pathophysiology and evolving histologic classifications is particularly useful for radiologists, as these influence tumor behavior, preferred imaging, therapy options, and patient prognosis.

Pancreaticoduodenectomy Is the Best Surgical Procedure for Zollinger-Ellison Syndrome Associated with Multiple Endocrine Neoplasia Type 1.

Simple SummaryApproximately 30% of patients with multiple endocrine neoplasia type 1 (MEN1) develop the Zollinger–Ellison syndrome (ZES), caused by solitary or multiple duodenal gastrinomas. Its management, especially regarding indication, timing, and type of surgery, is highly controversial. Therefore, the present study evaluated the long-term outcomes of pancreaticoduodenectomy (PD) versus non-PD resections in MEN1-ZES with regard to biochemical cure and quality of life. We found in a series of 35 patients that initial PD is the superior surgical procedure for MEN1-ZES, leading to long-term cure in about 80% of patients, fewer duodenopancreatic reoperations and an acceptable quality of life. Based on the results of this study, MEN1-ZES should be considered a surgically curable disease.Aim: The aim of this research was to evaluate the long-term outcome of pancreaticoduodenectomy (PD) versus other duodenopancreatic resections (non-PD) for the surgical treatment of the Zollinger–Ellison syndrome (ZES) in patients with multiple endocrine neoplasia type 1 (MEN1). Methods: Prospectively recorded patients with biochemically confirmed MEN1-ZES who underwent duodenopancreatic surgery were retrospectively analyzed in terms of clinical characteristics, complications, cure rate, and long-term morbidity, including quality of life assessment (EORTC QLQ-C30). Results: 35 patients (16 female, 19 male) with MEN1-ZES due to duodenopancreatic gastrinomas with a median age of 42 (range 30–74) years were included. At the time of diagnosis, 28 (80%) gastrinomas were malignant, but distant metastases were only present in one (3%) patient. Eleven patients (31.4%) underwent pancreatoduodenectomy (PD) as the initial procedure, whereas 24 patients underwent non-PD resections involving duodenotomy with gastrinoma excision, enucleation of the pNEN from the head of the pancreas, and peripancreatic lymphadenectomy, either with or without distal pancreatectomy (i.e., either Thompson procedure, n = 12, or DUODX, n = 12). There was no significant difference in perioperative morbidity and mortality between the two groups (p ≥ 0.05). One (9%) patient of the PD group required reoperation for recurrent or metastatic ZES compared to eight (22.8%) patients of the non-PD resection groups. After a median follow-up time of 134 months (range 6–480) nine of 11 (82%) patients in the PD group, two of 12 (16%) patients in the Thompson procedure group, and three of 12 (25%) patients in the DUODX group had normal serum gastrin levels. In addition, the global health QoLScore was better in the PD group (76.9) compared to the Thompson procedure (57.4) and DUODX (59.5) groups. Conclusions: Initial PD seems to be the superior surgical procedure for MEN1-ZES, resulting in a long-term cure rate of about 80%, fewer duodenopancreatic reoperations, and an acceptable quality of life.