Histologic features in an autoimmune gastritis patient with hypergastrinemia: Call for a grading system for G cell hyperplasia

Introduction/Objective Autoimmune gastritis (AG) is characterized by oxyntic glands destruction, metaplasia, enterochromaffin-like endocrine cell abnormality and G-cell hyperplasia with hypergastrinemia. The gastrin level can be extraordinarily high in certain cases to justify suspicion of Zollinger-Ellison syndrome. We herein report one such case and discuss clinical implication of a grading system for G-cell hyperplasia to correlate histology with gastrin levels. Methods/Case Report The patient was a symptomatic 65 year-old female with hypergastrinemia (2,068 pg/mL), negative abdomen/pelvis CT scan, positive anti-intrinsic factor and anti-parietal cell antibodies. Under esophagogastroduodenoscopy, biopsies were obtained from gastric cardia, fundus, corpus, incisura angularis, and antrum. Morphology and immunostains confirmed autoimmune gastritis. Diffuse linear pattern G-cell hyperplasia was evident in antrum and incisura angularis, counting up to 200 G-cells per linear millimeter. One study defined G-cell hyperplasia as >140 gastrin-positive cells per linear millimeter while another proposed a 2-tier stratification, i.e., simple hyperplasia (4-5 cells for each gland) and linear hyperplasia (continuous chain-like distribution of G-cells). Such scoring, however, was largely qualitative and fell short in delineating the extent of G-cell hyperplasia and correlation with gastrinemia. Results (if a Case Study enter NA) NA Conclusion Lack of G-cell grading system hindered our unequivocal determination of the G-cell hyperplasia as underlying or contributing cause of hypergastrenemia. The unique features of our case highlighted the necessity for installing a practical grading system that incorporates G-cell density, pattern (linear vs. nodular), extent of involved areas, other features of AG to correspond to gastrin level. With accumulation of clinical information, one such grading system is feasible and will improve our knowledge and patient care.

GASTRIN IN SERUM AND MORPHOLOGICAL STATE OF GASTRIN-SECRETING CELLS IN PATIENTS WITH GASTRIC POLYPOSIS

Objective. Numerous studies regarding gastric hormones and their regulation have been performed until now. However, the effect of the hormones on the formation and malignisation of gastric polyps still remains not clear. Our aim was to identify the relation between the level of gastrin in the blood, gastric mucosa, polyp tissue, gastric juice and pathogenesis of gastric polyposis. Materials and methods. A thorough investigation of gastrointestinal hormones in serum and gastric juice, in polyp’s tissue and mucosa, gastrin-secreting cells and proteolytic activity of gastric juice was carried out in 40 patients with gastric polyps. These patients were divided into groups, depending on the location, number, and malignancy of the polyps. As a control group, 10 healthy individuals were used to determine the normal values of the studied indicators. Results: A significant increase (more than two times) in the gastrinemia level before the surgery was noted in patients with polyp recurrence, and gastrin level increased to more significant digits of 227.0+37.4 pg/ml (p<0.05) in one year after polypectomy. Conclusion. Gastrin is apparently involved in the process of polyp formation since polyp’s growth is accompanied by elevation of serum gastrin. This is confirmed by a response of gastrin in the blood to a test meal in individuals with different duration of the disease: a marked increase in gastrinemia appears in patients suffering from gastric polyposis for more than three years. Therefore, evaluation of gastrin level in the patients’ blood can be used to predict a recurrence potential of polyps. This is evidenced by more pronounced hypergastrinemia before polypectomy in patients who had a further recurrence of the disease within one year after the surgery

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

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

Zollinger ellison syndrome due to primary nodal gastrinoma located outside the limits of the conventional gastrinoma triangle: report of a case

Primary nodal gastrinoma is a rare entity and the diagnosis is often contemplative when no other non - nodal primary site can be identified despite thorough investigations and operative exploration. Here we report one such case wherein a primary nodal gastrinoma was diagnosed as an entity of exclusion. Additionally, the location of the disease outside the confines of the conventional gastrinoma triangle further contributes to the rarity of the presentation. A young male patient had presented to us with history of multiple operations in the past for recurrent upper abdominal pain presumably consequential to peptic ulcer disease viz a trucal vagotomy and gastrojejunostomy, duodenal ulcer perforation surgery and a cholecystectomy. CT scan and endoscopic USG showed a preaortic calcified node located outside the limits of the gastrinoma triangle. A raised serum gastrin level and an endoscopic guided FNAC confirmed the diagnosis of a gastrinoma. A 68 Ga-DOTANOC PET CT revealed an exclusive nodal uptake with no discenable primary lesion. Normalization of gastrin levels after removal of the involved pre-aortic node further pointed to the diagnosis of primary nodal gastrinoma. A high index of clinical suspicion is warranted especially in a history of multiple surgeries for recurrent upper abdominal pain and location of the lesion outside the confines of the ‘Gastrinoma Triangle’ should not be deterrent for the diagnosis.

A case of early autoimmune gastritis with characteristic endoscopic findings

Significant atrophic gastritis in the fundic gland region is a well-known endoscopic finding observed in autoimmune gastritis (AIG). The endoscopic features of early AIG have not been reported. Iron deficiency, vitamin B12 deficiency, anemia, or neurological symptoms may not be observed in the early stages of AIG, and it may thus be difficult to diagnose early AIG based on clinical findings. We treated a 50-year-old Japanese female whose condition was suspected to be early AIG. The endoscopic findings showed normal gastric pyloric gland mucosa, and diffuse reddened and edematous gastric fundic gland mucosa. Pathologically, local infiltration of lymphocytes and decrease of parietal cells was present in a deep part of the gastric fundic gland mucosa. Blood tests showed that the titer of parietal cell antibody (PCA) was 1:320 and the gastrin level was 820 pg/ml. We determined that the patient had AIG because she also had Hashimoto’s disease, the PCA titer was high, the serum gastrin level was slightly increased, and inflammation was observed only in the gastric body on the endoscopic images. To the best of our knowledge, this is the first case report of endoscopic findings that suggest early AIG, before atrophic changes were observed.

Ultrastructural study of mucous cells of rat colon in long-term hypergastrinemia

Gastrin is considered one of the most important hormones regulating physiological processes. Trophic and proliferative effects of high gastrin levels on gastric mucosa are well known. Butinformation about gastrin effects on the colon is rather fragmentary and contradictory. In this study, ultrastructural changes in the proximal part of the colon induced in rats by chronic hypergastrinemia were analyzed by transmission electron microscopy. Experimental omeprazole-induced hypergastrinemia was reproduced using daily injections of proton pump inhibitor omeprazole in rats, resulted in hypersecrestion of gastrin by G-cells of stomach. Growth of gastrin level in the blood plasma was checked using radioimmunoassay method. Prolonged hypergastrinemia has been shown to be associated with increased cell proliferation and appearance of cellular atypia in the large intestine mucosa. The number of undifferentiated cells increased prominently. Intercellular contacts between such cells are altered, the space between them is unevenly expanded. Their organelles were observed significantly reduced, mitochondria contained destroyed crysts and signs of edema. Endocrinocytes did not contain their typical secretory granules. Cell nuclei were small, electron-dense, with invagination. In addition, numerous microorganisms were revealed in the intestinal lumen, as well as their invasion into the mucosa. Those ultrastructural changes were indicate increased hyperplastic processes and impaired cell differentiation in the epitheliocytes of large intestine. Therefore, long-term experimental hypergastrinaemia causes dysplastic changes in the large intestine mucosa of rats.

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

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

Proton Pump Inhibitors and Radiofrequency Ablation for Treatment of Barrett's Esophagus

Gastroesophageal Reflux Disease (GERD) is characterized by acid and bile reflux in the distal oesophagus, and this may cause the development of reflux esophagitis and Barrett’s oesophagus (BE). The natural histological course of untreated BE is non-dysplastic or benign BE (ND), then lowgrade (LGD) and High-Grade Dysplastic (HGD) BE, with the expected increase in malignancy transfer to oesophagal adenocarcinoma (EAC). The gold standard for BE diagnostics involves high-resolution white-light endoscopy, followed by uniform endoscopy findings description (Prague classification) with biopsy performance according to Seattle protocol. The medical treatment of GERD and BE includes the use of proton pump inhibitors (PPIs) regarding symptoms control. It is noteworthy that long-term use of PPIs increases gastrin level, which can contribute to transfer from BE to EAC, as a result of its effects on the proliferation of BE epithelium. Endoscopy treatment includes a wide range of resection and ablative techniques, such as radio-frequency ablation (RFA), often concomitantly used in everyday endoscopy practice (multimodal therapy). RFA promotes mucosal necrosis of treated oesophagal region via high-frequency energy. Laparoscopic surgery, partial or total fundoplication, is reserved for PPIs and endoscopy indolent patients or in those with progressive disease. This review aims to explain distinct effects of PPIs and RFA modalities, illuminate certain aspects of molecular mechanisms involved, as well as the effects of their concomitant use regarding the treatment of BE and prevention of its transfer to EAC.

A Comparison of Baseline Clinical Characteristics of Autoimmune Gastritis Patients with and without Type-1 Gastric Carcinoid Tumor

Objectives : Autoimmune gastritis (AIG) is an antibody-mediated autoimmune disease and characterized by gastric parietal cell loss. Type-1 gastric carcinoid tumor (GCT) is a disease that mostly develops on the basis of AIG. The aim of this study is to determine similarities and differences of baseline clinical parameters between these two disorders. Methods: Patients diagnosed as AIG both without gastric carcinoid tumor (n:197) and with GCT (n:40) between 2004 and 2015 at Ankara University Faculty of Medicine, Department of Gastroenterology, were included in this analysis. Data of initial signs and symptoms, basal blood count-anemia parameters, laboratory investigations, serum gastrin levels, anti parietal cell antibody (APCA) status, serological helicobacter pylori (Hp) markers and serum chromogranine A (CgA) levels of patients were obtained, and baseline parameters of these disorders were compared Results: Patient groups were similar in age and gender. Hemoglobin, iron, total iron binding capacity (TIBC), ferritin, vitamin B12 levels, APCA and HpIgG positivity rates and concomitant autoimmune thyroid disease prevalence were also similar. Median gastrin level in AIG+GCT patients was significantly higher compared to the AIG without GCT (807 vs. 1307 pg/ml; p:0.006). ROC analysis revealed that a 1000 pg/ml threshold value for serum gastrin level is able to distinguish these two disorders with 65% sensitivity and 65% specificity rates (area under the curve: 0.65;p:0.006). The serum CgA level did not significantly differ between patient groups. Conclusion: High serum gastrin but not CgA levels may be useful in deciding which patients should be followed closely in AIG.