Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective.

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological-psychiatric up to gastrointestinal and less commonly to gynecological-obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.

[Characteristics of gastric neuroendocrine tumors and the PDX-1 transcription factor expression]. / Kharakteristika neiroendokrinnykh opukholei zheludka i ekspressiya v nikh transkriptsionnogo faktora PDX-1.

OBJECTIVE: To study the features of gastric neuroendocrine tumors (NETs) and the diagnostic and prognostic significance of PDX-1 expression in them. MATERIAL AND METHODS: 207 NETs identified in 56 men and 115 women (59 had multiple NETs), and 94 cases of gastric cancer (comparison group) were studied morphologically and immunohistochemically. RESULTS: In more than half of the cases (54.93%), NETs were localized in the body of the stomach; the cardiac and antral parts of the stomach accounted for 8.64% and 11.73%, respectively. NETs of the cardiac region predominated in men, and of the body and antrum - in women. NETs of the cardiac region predominated in men, and of the body and antrum - in women. The vast majority of NETs were highly differentiated (89.20%), of which Grade 1, 2 and 3 were 55.41%, 40.76% and 3.82%, respectively. Neuroendocrine carcinomas (NEC) accounted for 10.80% of all NET cases. NECs were more often localized in the cardiac part of the stomach and accounted for 35.71% of all NETs in the cardiac part. The share of NEC among all NETs of the antrum was 15.79%, of the body of the stomach - only 3.37%. Metastases were found in 17.90% of NETs. Expression of PDX-1 was detected in 44.73% of NETs, 70% of NECs and 74.50% of gastric cancers. CONCLUSION: PDX-1 is involved in the mechanisms of precancerous and cancerous lesions of the stomach and its overexpression is detected in the majority of the most malignant NETs and gastric cancers.

Management of type 1 gastric neuroendocrine tumors: an 11-year retrospective single-center study.

BACKGROUND: Type 1 gastric neuroendocrine tumors (NETs) are relatively rare to the extent that some physicians have little experience in diagnosing and treating them. The purpose of this study was to increase the understanding of the disease by analyzing and summarizing the management and prognoses of patients with type 1 gastric NETs at our center. METHODS: The data of 229 patients (59.4% female) with type 1 gastric NETs who were treated at our center during 2011-2022 were retrospectively analyzed. RESULTS: The average patient age was 50.5 ± 10.8 years. Multiple tumors affected 72.5% of the patients; 66.4% of the tumors were < 1 cm, 69.4% were NET G1, and 2.2% were stage III-IV. A total of 76.9% of the patients had received endoscopic management, 60.7% had received traditional Chinese medicine treatment, 10.5% received somatostatin analogues treatment, and 6.6% underwent surgical resection. Seventy patients (41.2%) experienced the first recurrence after a median follow-up of 31 months (range: 2-122 months), and the median recurrence-free time was 43 months. The 1-, 2-, and 3-year cumulative recurrence-free survival rates were 71.8%, 56.8%, and 50.3%, respectively. During a median follow-up of 39 months (range: 2-132 months), one patient had bilateral pulmonary metastasis, and no disease-related deaths were observed. CONCLUSION: Type 1 gastric NETs have a high recurrence rate and a long disease course, underscoring the importance of long-term and comprehensive management.

Gastric lesions in patients with autoimmune metaplastic atrophic gastritis: a retrospective study in a single center.

OBJECTIVES: The presence of autoimmune metaplastic atrophic gastritis (AMAG) may lead to an increased risk of associated gastric neoplastic lesions. This study aims to investigate the prevalence of gastric neoplasia in AMAG patients and to explore the possibility of PGI/II ratio as a predictor for AMAG diagnosis. PATIENTS AND METHODS: Retrospective audit of 135 patients diagnosed with AMAG on endoscopic gastric biopsy between January 2017 and December 2020 at Beijing Friendship Hospital. The study was registered in Chinese Clinical Trial Registry (ChiCTR2000041163). RESULTS: A total of 135 patients (the mean age 61.9 ± 10.9 years,109 female) had histologically confirmed AMAG. 31.1% (42/135) had AMAG without neoplasia on the initial biopsy; 37% (50/135) had multiple type 1 gastric neuroendocrine tumors (g-NETs), 36 grade 1 and 14 grade 2, the median diameter was 5 mm (range 1-25); 31.9% (43/135) had multiple gastric hyperplastic polyps (GHPs), including 15 cases of GHPs with neoplastic transformation, the median diameter was 14.5 mm (range 3-50). 3.7% (5/135) had single gastric low-grade dysplasia/adenoma, the median diameter was 5 mm (range 3-15). 5.9% (8/135) had single or double gastric high-grade dysplasia or adenocarcinoma, the median diameter was 15 mm (range 8-43). 40.7% (55/135) had pepsinogen (PG) I< 10 ng/ml, 45.9% (62/135) had PG I/II ratio ≤1 and each group had a median of PG I/II ratio <1. CONCLUSIONS: Lower serum PG I level and PGI/II ratio may be a predictor to indicate the diagnosis of AMAG. It's necessary to perform regular endoscopic surveillance for AMAG patients to recognize associated gastric neoplasia timely.

Effects of tumor types on treatment strategy formulation and prognostic evaluation of gastric neuroendocrine tumors.

Aim: The effects of different types of gastric neuroendocrine tumors (G-NETs) on treatment strategy formulation and prognostic evaluation still remain controversial due to their rarity. Methods: 187 patients diagnosed with G-NETs were subdivided into four types based on the pathophysiology, etiology and presentation. Results: Type I, II G-NETs >1.0 cm and type III, IV G-NETs >2.0 cm are proved with aggressive behavior (p < 0.05). Type III G-NETs with higher Ki-67 index and tumor stage showed more invasive potential than type I and II G-NETs (p < 0.05). Endoscopic resection is the primary treatment for type I, II G-NETs, while surgical combined with chemotherapy is associated with favorable outcomes for type IV G-NETs. Conclusion: The clinical classifications of G-NETs are of great significance for the choice of treatment and the evaluation of prognosis.

[Gastric neuroendocrine tumors]. / Neiroéndokrinnye opukholi zheludka.

Gastrointestinal neuroendocrine tumors are rare neoplasms. Currently, incidence of gastric neuroendocrine tumors (gNETs) is being significantly increased. There are 3 groups of gNETs: types I, II and III. Each type has important features regarding clinical picture, prognosis and treatment strategy. Type I is the most common (70-80%) and associated with chronic atrophic gastritis including autoimmune gastritis and Helicobacter associated atrophic gastritis. Type II (5-6%) is associated with multiple endocrine neoplasia type I and Zollinger-Ellison syndrome (MEN I - ZES). Both types are characterized by hypergastrinemia and small tumor dimension. These neoplasms are multiple and mostly benign. On the contrary, NETs type III (10-15%) is not associated with hypergastrinemia and represented by single large neoplasms. Tumors are malignant as a rule. Therefore, surgical resection and chemotherapy are preferred for these tumors. Endoscopic surgery followed by observation is acceptable for almost all NETS type I and II. At the same time, this approach is advisable only for small and highly differentiated neoplasms type III.

Gastric Neuroendocrine Tumors (G-Nets): Incidence, Prognosis and Recent Trend Toward Improved Survival.

BACKGROUND/AIMS: Gastric neuroendocrine tumors (G-NETs) are uncommon neoplasms that can present with or without clinical symptoms. In this study, we evaluated the incidence, prognosis, and temporal trends of G-NETs. METHODS: We analyzed all cases of G-NETs registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2014. Incidence was estimated by age and joinpoint analyses. Survival rates were calculated and survival trends over time were evaluated. RESULTS: A total of 3740 eligible patients were enrolled in the study. G-NETs incidence increased from 0.31 per 1 000 000 patients in 1975 to 4.85 in 2014, with an annual percentage changes (APCs) of 8.9% (95% confidence interval [CI] = 7.7% to 10.21%, P < 0.001, t test (29) from 1975 to 2001 and 3.6% from 2002 to 2014 (95% CI= 2.3% to 4.9%, P < 0.001). For cases diagnosed between 1973 and 1982, five-year survival was 62.8% ± 7.0% (Standard error, SE) and increased to 86.7% ± 0.7% for cases diagnosed between 2003 and 2012 (P < 0.001). Years of diagnosis, gender, age at diagnosis, marital status, grade, tumor size, tumor stage, and surgery performed or not were the strongest predictors of worse survival in both univariate and multivariate analysis (P<0.05). CONCLUSION: G-NETs are uncommon neoplasms but the incidence is growing. Survival has improved in the past decades. Years of diagnosis, gender, age at diagnosis, marital status, grade, tumor size, tumor stage, and surgery status predict survival in patients with G-NETs.

Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?

OBJECTIVE: Reporting on three cases of gastric neuroendocrine tumors (g-NETs) in patients taking long-term proton pump inhibitors (PPIs). These tumors are not classifiable considering current criteria. g-NETs are currently grouped as: types 1 and 2, related to hypergastrinemia due to chronic atrophic gastritis and Zollinger-Ellison syndrome respectively, and type 3, normogastrinemic and more aggressive. Although the g-NETs onset in patients taking PPIs is biologically plausible, only a few cases have been reported so far. MATERIALS AND METHODS: From January 2005 to July 2014, 31 g-NETs were referred to our Unit: 24 (77%), one (3%) and three (10%) resulted types 1, 2 and 3, respectively. Three cases (10%) did not meet the current classification criteria. RESULTS: The three patients were administered long-term PPIs for gastro-esophageal reflux disease. Patient 1: a 78-year-old man, with a 4-mm well-differentiated g-NET (Ki-67<1%) and marked hypergastrinemia. Patient 2: a 58-year-old man affected by a 6-mm well-differentiated (Ki-67 = 4%) g-NET, with normal gastrin levels. Patients 3: a 67-year-old woman with an 18-mm well-differentiated g-NET (Ki-67 <2%), with mild hypergastrinemia. In the three patients, histology and pertinent blood tests excluded chronic atrophic gastritis, Helicobacter pylori infection or Zollinger-Ellison syndrome. The first two patients underwent endoscopic polypectomy; in the third case total gastrectomy was performed. Further clinical, endoscopic and imaging follow-up did not show any g-NET recurrence. CONCLUSIONS: The present data point to the existence and epidemiological relevance of g-NETs associated with PPIs intake. These neoplasms are not included in the current classification, thus their treatment and follow-up have not been established.

Predictors of Outcomes in Gastric Neuroendocrine Tumors: A Retrospective Cohort.

Introduction/Aim: Gastric neuroendocrine tumors (GNETs) frequently have an indolent clinical course, despite their metastatic potential. The aim of the study was to identify prognostic factors associated with overall survival and risk of metastases and to evaluate the impact of serial measurements of chromogranin A (CgA). Methods: The authors performed a retrospective cohort study including consecutive patients with GNET diagnosed between 2010 and 2019, with a minimum follow-up of 1 year. Univariate and multivariate analyses were performed. Results: We included 132 patients with GNET (type I, 113 patients; type II, 1 patient; type III, 14 patients; type IV, 2 patients; not classifiable, 2 patients), with 61% being female and a mean age at diagnosis of 66 years. During the follow-up period (median 66 months), 3 (2.3%) patients died due to metastatic disease (1 patient with type III and 2 patients with type IV). Male gender (p = 0.030), type III/IV (p < 0.001), Ki-67 index >20% (p < 0.001), grade 2/3 (p < 0.001), invasion beyond the submucosa (p < 0.001), and presence of metastases (p < 0.001) were identified as risk factors for mortality in the univariate analysis. Metastasis developed in 7 patients (5.3%). Multivariable analysis revealed that Ki-67 >20% (p = 0.016) was an independent risk factor for metastasis. Overall, CgA showed a sensitivity of 20% for detection of recurrence and a specificity of 79% (sensitivity of 8% and specificity of 71% in type I GNETs). Conclusion: Identification of risk factors for the presence of metastases and for mortality in these groups of patients can help in individualizing the therapeutic strategy. CgA seems to be a weak marker for monitoring patients with GNET.

Introdução/Objetivo: Os tumores neuroendócrinos gástricos (TNEs-G) têm frequentemente um curso indolente, apesar do seu potencial metastático. O objetivo deste trabalho foi identificar fatores de prognóstico associados à sobrevida global e à metastização nos doentes com TNEs-G e avaliar o impacto da análise seriada de cromogranina A (CgA). Methods: Estudo retrospectivo incluindo doentes consecutivos admitidos por TNE-G entre 2010 e 2019, com um follow-up mínimo de 1 ano. Foi realizada análise univariada e multivariada. Results: Foram incluídos 132 doentes com TNE-G (Tipo I, 113 doentes; Tipo II, 1 doente; Tipo III, 14 doentes; Tipo IV, 2 doentes; Não classificável, 2 doentes), sendo 61% mulheres, com idade média de 66 anos. Durante o periodo de follow-up (mediana 66 meses), 3 (2.3%) doentes faleceram por doença metastática (1 doente com Tipo III e 2 com Tipo IV). O sexo masculino (p = 0,030), tipo III/IV (p < 0,001), Ki-67 index >20% (p < 0,001), Grau 2/3 (p < 0,001), invasão além da submucosa (p < 0,001) e presença de metástases (p < 0,001) foram identificados como fatores de risco para mortalidade na análise univariada. Sete doentes desenvolveram metástases (5,3%). A análise multivariáda revelou que o Ki-67 >20% (p = 0,016) era um factor de risco independente para metastização.Globalmente, a CgA mostrou uma sensibilidade de detecção de recorrência de 20% e uma especificidade de 79% (sensibilidade de 8% e especificidade de 71% em em TNEs-G do Tipo I). Conclusão: A identificação dos fatores de risco para a presença de metástases e para a mortalidade neste grupo de pacientes pode ajudar a individualizar a estratégia terapêutica. A CgA parece ser um marcador fraco para a monitorização de doentes com TNEs-G.

Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis.

OBJECTIVE: This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g-NENs). METHODS: A retrospective enrollment of 142 patients diagnosed with g-NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (g-NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). RESULTS: The study comprised a total of 142 g-NENs cases, with a male-to-female ratio of approximately 2:1. The 5-year survival rates for g-NEC and g-MiNEN were 26.7% and 35.2%, respectively. Corresponding 5-year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g-NEC/MiNEN showed a significantly worse prognosis compared to g-NET (p < 0.001). g-NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g-NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g-NEC/MiNEN (p = 0.010). CONCLUSION: In short, the prognosis of g-NEC/MiNEN was worse than that of g-NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.

Gastric Neuroendocrine Tumor With Cystic Hepatic Metastases Mimicking Hepatic Echinococcosis: A Case Report.

Metastatic gastrointestinal neuroendocrine tumors classically appear as contrast-enhancing lesions on computed tomography. However, in a small percentage of patients, these lesions can be cystic in nature, leading to false diagnoses of benign or infectious lesions such as echinococcosis. Hence, every cystic lesion of the liver must be carefully investigated before making the treatment plan. We report a patient with hematemesis caused by a large gastric ulcer with multiple cystic lesions in the left lobe of the liver abutting the stomach. The liver lesions were misdiagnosed as hepatic echinococcosis, and the patient was started on medical therapy. However, when medical therapy failed, the patient underwent surgical excision and the histopathology showed cystic metastases of a gastric neuroendocrine tumor.

Chronic Treatment with Somatostatin Analogues in Recurrent Type 1 Gastric Neuroendocrine Tumors.

BACKGROUND: Type 1 gastric neuroendocrine tumors (GC-1) represent an uncommon subtype of neoplasms. Endoscopic resection has been proposed as the treatment of choice; active surveillance may be performed in those smaller than 1 cm, while gastric surgery may be performed for those with frequent recurrences. The antiproliferative effect of somatostatin analogues (SSA) is well known, and their action on GC-1s has been postulated as a chronic treatment to reduce recurrence. METHODS: A two-centered, retrospective, observational study that included nine patients (55.6% women) diagnosed with GC-1, receiving long-term treatment with SSA, with a median follow-up from baseline of 22 months, was undertaken. Endoscopic follow-up, extension study, and analytical values of chromogranin A (Cg A) and gastrin were collected. RESULTS: In total, 88.9% of patients presented partial or complete response. Treatment with SSA was the only independent factor with a trend to prevent tumor recurrence (Odds Ratio 0.054; p = 0.005). A nonsignificant tendency toward a decrease in CgA and gastrin was observed; lack of significance was probably related to concomitant treatment with proton pump inhibitors in some patients. CONCLUSIONS: Chronic treatment with SSA is a feasible option for recurrent GC-1s that are difficult to manage using endoscopy or gastrectomy. Randomized clinical trials to provide more scientific evidence are still needed.

Incidence and prevalence of gastric neuroendocrine tumors in patients with chronic atrophic autoimmune gastritis.

BACKGROUND: The incidence of type I gastric neuroendocrine neoplasms (gNENs) has increased significantly over the past 50 years. Although autoimmune gastritis (AIG) increases the likelihood of developing gNENs, the exact incidence and prevalence of this association remain unclear. AIM: To evaluate the incidence and prevalence of type I gNENs in a cohort of patients with a histological diagnosis of AIG. METHODS: Patients with a histological diagnosis of AIG were enrolled between October 2020 and May 2022. Circulating levels of CgA and gastrin were assessed at enrollment. Included patients underwent regular endoscopic follow-up to detect gastric neoplastic lesions, enterochromaffin-like (ECL) cell hyperplasia, and the development of gNEN. RESULTS: We included 176 patients [142 women (80.7%), median age 64 years, interquartile range (IQR) 53-71 years] diagnosed with AIG between January 1990 and June 2022. At enrollment. One hundred and sixteen patients (65.9%) had ECL hyperplasia, of whom, 29.5% had simple/linear, 30.7% had micronodular, and 5.7% had macronodular type. The median follow-up time was 5 (3-7.5) years. After 1032 person-years, 33 patients developed a total of 50 type I gNENs, with an incidence rate of 0.057 person-years, corresponding to an annual cumulative incidence of 5.7%. Circulating CgA levels did not significantly differ between AIG patients who developed gNENs and those who did not. Conversely, gastrin levels were significantly higher in AIG patients who developed gNENs [median 992 pg/mL IQR = 449-1500 vs 688 pg/mL IQR = 423-1200, P = 0.03]. Calculated gastrin sensitivity and specificity were 90.9% and 1.4%, respectively, with an overall diagnostic accuracy of 30% and a calculated area under the gastrin receiver operating characteristic curve (AUROC or AUC) of 0.53. CONCLUSION: Type I gNENs are a significant complication in AIG. Gastrin's low diagnostic accuracy prevents it from serving as a marker for early diagnosis. Effective strategies for early detection and treatment are needed.

Clinicopathologic features of non-type 1/2 gastric neuroendocrine tumors and their associated mucosal changes.

OBJECTIVES: The pathogenesis for non-type 1/2 gastric neuroendocrine tumors (G-NETs) remains unclear. The aim of this study was to examine the clinicopathologic features of G-NETs and associated mucosal changes. METHODS: The electronic health records of patients with non-type 1/2 G-NETs were reviewed. H&E slides were reviewed for pathologic features and mucosal changes. The t test and Fisher exact test were used for statistical analysis. RESULTS: In total, 33 patients were assigned to either group 1 (n = 23) or group 2 (n = 10). Group 1 included patients with a history of proton pump inhibitor (PPI) use, increased gastrin levels, or significant PPI effect (PPI/gastrin-associated). All other patients were assigned to group 2. There was no significant difference in age and sex between the 2 groups. Group 2 tumors were more likely to be larger, invade deeper, and develop metastases (P < .05). Tumors in patients with cirrhosis tended to be larger. Peritumoral mucosal changes included loss of oxyntic glands, foveolar hyperplasia, and intestinal metaplasia. Background mucosa in group 1 patients showed PPI effect and neuroendocrine hyperplasia or dysplasia. CONCLUSIONS: Although PPI/gastrin-associated non-type 1/2 G-NETs were smaller and more indolent than typical type 3 G-NETs, tumors in patients with cirrhosis tended to be larger. Additionally, peritumoral mucosal changes could mimic chronic atrophic gastritis.

Defining prognostic parameters of well-differentiated gastric neuroendocrine tumors based on metastatic potential: a two-center experience.

Background: Gastric neuroendocrine tumors [gNETs] are heterogeneous tumors and we are still unable to predict the behavior of these tumors. We aim to define the prognostic parameters of well-differentiated gNETs based on metastatic potential and to evaluate the current classification systems. Patients and methods: We retrospectively retrieved 44 well differentiated gNET cases who underwent radical surgery between 2000-2015 at two tertiary-care centers. Results: Among the 44 well-differentiated gNET patients, 17 (38%) patients had metastatic disease to lymph nodes and/or distant sites, while 27 (62%) were confined to the stomach. Higher risk of metastasis was observed with increasing tumor size, grade, depth of invasion and with type-3 and solitary tumors. 30 (68%) patients had type-1 gNET and 14 (32%) had type-3 gNET. Majority of the type-1 cases (76,6%) were Grade 1 [G1] and type-3 cases (78,5%) were Grade 3 [G3]. Type-1 subgroup had no G3 tumor, and type-3 had no G1. Grade 2 [G2] tumors were more controversial, with metastatic and non-metastatic cases. G2 cases with a >10% Ki67 expression or type-3, had a worse prognosis. Although most of the type-1 gNETs had an indolent course, 6 of 30 (20%) patients had metastatic disease. Metastasizing type-1 gNETs were >10 mm in diameter or extended to/beyond the submucosa. Conclusion: Regarding our results, tumor type, grade, size, focality and depth of invasion are the prognostic parameters for gNETs, based on metastatic potential. Besides these parameters, a two-tiered grading system with a 10% Ki-67 proliferation index cut-off value could be considered for right treatment choice.

Type-1 Grade 2 Multi-Focal Gastric Neuroendocrine Tumors Secondary to Chronic Autoimmune Gastritis.

Background: Chronic autoimmune gastritis (CAG) refers to chronic atrophic gastritis due to autoimmunity. Loss of gastric glands in CAG results in hypergastrinemia and achlorhydria leading to Vitamin B12 deficiency and hyperplasia of G cells and enterochromaffin-like (ECL) cells. Vitamin B12 deficiency could cause pernicious anemia and subacute combined degeneration, while G cells and ECL cells hyperplasia might develop gastric neuroendocrine tumor (G-NET). Case Presentation: A 35-year-old Chinese female presented with multi-focal type-1 Grade 2 (G2) NETs with a 14-year history of pernicious anemia and subacute combined degeneration. Conclusion: Here, we report a rare case of a Chinese patient presenting G-NET combined with pernicious anemia and subacute combined degeneration, which are secondary to chronic autoimmune gastritis. This case also illustrates the importance of routine gastroscopy in patients with Vitamin B12 deficiency.

Type I Gastric Neuroendocrine Tumor Presenting as Acute Upper Gastrointestinal Bleed.

Gastric neuroendocrine tumors (GNETs) are rare and subdivided into type I, type II, and type III. Types I and II are gastrin-dependent and are usually benign, whereas type III is gastrin-independent and more aggressive. Type I accounts for 70-80% of all GNETs. Most of them are asymptomatic and incidentally detected on endoscopy. It can sometimes present with iron and B12 deficiency, dyspepsia, and less commonly with an upper GI bleed. We present a case of type I GNET who came to the hospital with melena and esophagogastroduodenoscopy (EGD) showing a 3-cm bleeding polyp and histopathology revealing a well-differentiated neuroendocrine tumor with angioinvasion.

Gastric neuroendocrine neoplasms: A review.

Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.

Alterations in SLC4A2, SLC26A7 and SLC26A9 Drive Acid-Base Imbalance in Gastric Neuroendocrine Tumors and Uncover a Novel Mechanism for a Co-Occurring Polyautoimmune Scenario.

Autoimmune polyendocrine syndrome (APS) is assumed to involve an immune system malfunction and entails several autoimmune diseases co-occurring in different tissues of the same patient; however, they are orphans of its accurate diagnosis, as its genetic basis and pathogenic mechanism are not understood. Our previous studies uncovered alterations in the ATPase H+/K+ Transporting Subunit Alpha (ATP4A) proton pump that triggered an internal cell acid-base imbalance, offering an autoimmune scenario for atrophic gastritis and gastric neuroendocrine tumors with secondary autoimmune pathologies. Here, we propose the genetic exploration of APS involving gastric disease to understand the underlying pathogenic mechanism of the polyautoimmune scenario. The whole exome sequencing (WES) study of five autoimmune thyrogastric families uncovered different pathogenic variants in SLC4A2, SLC26A7 and SLC26A9, which cotransport together with ATP4A. Exploratory in vitro studies suggested that the uncovered genes were involved in a pathogenic mechanism based on the alteration of the acid-base balance. Thus, we built a custom gene panel with 12 genes based on the suggested mechanism to evaluate a new series of 69 APS patients. In total, 64 filtered putatively damaging variants in the 12 genes of the panel were found in 54.17% of the studied patients and none of the healthy controls. Our studies reveal a constellation of solute carriers that co-express in the tissues affected with different autoimmune diseases, proposing a unique genetic origin for co-occurring pathologies. These results settle a new-fangled genetics-based mechanism for polyautoimmunity that explains not only gastric disease, but also thyrogastric pathology and disease co-occurrence in APS that are different from clinical incidental findings. This opens a new window leading to the prediction and diagnosis of co-occurring autoimmune diseases and clinical management of patients.

Multiple Small Intestinal Neuroendocrine Tumors With Findings of Intestinal Obstruction.

Carcinoid tumors are one of the most common types of small intestinal neuroendocrine tumors (SI-NETs). However, SI-NETs that manifest as subacute intestinal obstruction are extremely rare. The annual occurrence rate of jejuno-ileal NETs is 0.28-0.8 per 100,000 people. In this report, we describe a case of subacute intestinal obstruction due to a mid-ileal stricture. The patient underwent laparotomy after evaluation and investigation. Mid-ileal growth was noted, and small bowel resection was performed with primary end-to-end anastomosis. Postoperative histopathology revealed the growth to be a well-differentiated NET.