Comprehensive clinicopathologic features in autoimmune atrophic gastritis: Insights from a European cohort of 57 patients.

CONTEXT: Autoimmune atrophic gastritis (AAG) is a frequently underdiagnosed disease due to its broad-spectrum clinical presentation. The diagnosis is based on histological confirmation of corpus-restricted metaplastic chronic atrophic gastritis. OBJECTIVE: To thoroughly describe the histological features of a European cohort of AAG patients. DESIGN: Clinical and pathological data of 57 out of 676 patients diagnosed with AAG were reviewed. RESULTS: Thirty-nine patients were female and eighteen were male. The mean age was 62 years. Antibodies were identified in 32/42 patients (76 %). Vitamin B12 levels were low (< 200 pg/mL) in 37/54 patients (69 %). Serum gastrin levels was elevated (> 115 pg/mL) in all cases tested. Associated autoimmune/inflammatory conditions were identified in 20/57 patients (35 %). Histologically, deep chronic inflammation was present in 46/57 (81 %) patients. Complete destruction of oxyntic glands was observed in 45/57 (79 %) patients. Pyloric metaplasia was present in 54/57 (95 %) patients, intestinal metaplasia in 51/57 (89 %) patients, and pancreatic metaplasia in 20/57 (35 %) patients. Among ECL cell proliferation, linear hyperplasia was present in all 57/57 patients, micronodular hyperplasia in 55/57 patients, and adenomatoid hyperplasia in 10/57 patients. ECL cell dysplasia was identified in 5/57 patients, and neuroendocrine microtumor in 4/57 patients. CONCLUSIONS: The diagnosing of AAG remains challenging due to the greater variability in symptoms than previously recognized. It is important to consider chronic AAG, especially with other concurrent autoimmune conditions. The importance of accurate diagnosis and surveillance is based on the potential development of type 1 gastric neuroendocrine tumor and increased risk of gastric adenocarcinoma.

Unveiling Cancer-Related Metaplastic Cells in Both Helicobacter pylori Infection and Autoimmune Gastritis.

BACKGROUND & AIMS: Gastric metaplasia may arise as a consequence of chronic inflammation and is associated with an increased risk of gastric cancer development. Although Helicobacter pylori (Hp) infection and autoimmune gastritis (AIG) both induce gastric metaplasia, possible distinctions in resulting metaplastic cells and their respective cancer risks requires further investigation. METHODS: Using both mouse models and human participants, we scrutinized the metaplasia originating from Hp infection and AIG. Gastric pathology and metaplasia were examined through histopathologic assessment. Molecular features of metaplastic cells were defined using single-cell transcriptomics in murine models of Hp infection and AIG, as well as in human biopsy specimens from patients with Hp infection and AIG. Expression of a newly defined cancer-related metaplastic biomarker was confirmed through immunofluorescence. RESULTS: Metaplasia in Hp infection and AIG displayed comparable histopathologic and transcriptional features. Diverse metaplastic subtypes were identified across both disease settings, with subtle differences in the prevalence of certain subtypes between inflammatory contexts. Notably, Hp infection did not drive a unique metaplastic cell phenotype. One metaplastic subtype, which resembled incomplete intestinal metaplasia and shared transcriptional features with gastric cancer, was identified in both diseases. This cancer-like metaplastic subtype was characterized by expression of the cancer-associated biomarker alanyl aminopeptidase N/CD13. CONCLUSION: Both Hp infection and AIG trigger a diverse array of metaplastic cell types. Identification of a cancer-related metaplastic cell uniquely expressing alanyl aminopeptidase N/CD13, present in both Hp- and AIG-induced gastritis, indicates the carcinogenic capacity of both diseases. This discovery can guide early detection and risk stratification for patients with chronic gastritis.

Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion.

A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.

Occurrence and characteristics of endoscopic gastric polyps in patients with autoimmune gastritis (AGAPE study): A multicentric cross-sectional study.

BACKGROUND: Autoimmune gastritis (AIG) leads to increased gastrin (G) levels due to hypo-achlorhydria, providing proliferative stimuli on the gastric mucosa. AIMS: To evaluate the incidence and characteristics of gastric polyps in AIG patients across six tertiary centers in Italy. METHODS: A multicentric, cross-sectional study enrolled patients with AIG diagnosed from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, and endoscopic and histopathological findings were systematically collected. RESULTS: Among 612 AIG patients followed for a median of 4 years, 222 (36.3 %) developed at least one gastric polyp. Of these, 214 were non-endocrine lesions detected in 162 patients, including 151 inflammatory (70.5 %), 29 adenomatous (13.6 %), 18 fundic gland polyps (8.4 %), 13 adenocarcinomas (6.1 %), and one MALT lymphoma. Additionally, 108 patients had gastric neuroendocrine neoplasms (gNENs), with 48 also having non-endocrine polyps. Older age and higher gastrin and chromogranin A levels were associated with polyp occurrence. No differences in OLGA/OLGIM stages or Helicobacter pylori status were noted among patients with and without lesions. CONCLUSION: This large multicentric study underscores the substantial occurrence of gastric polyps in AIG patients, including notable rates of gNENs and adenocarcinomas, emphasizing the importance of proactive endoscopic surveillance and histopathological examination for effective management.

Improving the Diagnosis of Autoimmune Gastritis: From Parietal Cell Antibodies to H+/K+ ATPase Antibodies.

Parietal cell autoantibodies (PCAs), which recognize the enzyme H+/K+-ATPase as a target, are considered to be a diagnostic marker of autoimmune gastritis and pernicious anemia; these conditions are characterized by the presence of corpus atrophic gastritis. Circulating PCAs can be detected using several analytical methods that are commonly available in the clinical laboratory. Traditionally, indirect immunofluorescence (IIF) on rodent or primate stomach tissue is used as a screening test for the detection of PCAs. However, IIF suffers from a high inter-observer variability and lacks standardization. In addition, like immunoblotting, results are expressed only in a qualitative or semi-quantitative manner. Based on the few available studies that are reviewed herein, quantitative enzyme-linked immunosorbent assays (ELISAs) and fluorescence enzyme immunoassays (FEIAs) using purified H+/K+-ATPase perform better than IIF in the detection of PCAs, displaying higher sensitivity and utility in monitoring the disease. In light of their higher diagnostic accuracy, these solid-phase methods should be preferred to IIF in the screening of autoimmune atrophic gastritis. The use of methods to detect antibodies versus a specific subunit of H+/K+-ATPase (α or ß) is currently confined to the world of research. Further investigation is required to define the clinical utility of H+/K+-ATPase subunit detection.

Gastric Adenocarcinoma in Helicobacter pylori-Negative Autoimmune Gastritis: A Case Report and Literature Review.

Recent studies have suggested that gastric cancer does not occur in patients with Helicobacter pylori-negative autoimmune gastritis (AIG); however, this notion is controversial. We encountered a case of gastric cancer associated with AIG in which H. pylori infection was excluded. A woman in her 70s was referred to our hospital for endoscopic resection of an antral adenoma. An H. pylori antibodies test, stool antigens test, H. pylori culture, and histological analysis using Giemsa staining yielded negative results. AIG was suspected because the antrum was endoscopically normal but the body was severely atrophic, which are typical findings of AIG. Anti-parietal cell antibodies were 40-fold positive, the gastrin level was 2950 pg/ml, and the pepsinogen I level, pepsinogen II level, and pepsinogen I/II ratio were 6.3 ng/ml, 5.7 ng/ml, and 1.1, respectively. A pathological examination of the gastric body revealed severe oxyntic atrophy with hyperplasia of enterochromaffin-like cells, whereas the antrum showed no pyloric gland atrophy or inflammation. These findings indicated that the patient had H. pylori-negative AIG. Four years later, a depressed lesion in the lower body and a flat lesion at the angle were observed; the former was a poorly cohesive carcinoma, and the latter was a differentiated adenocarcinoma. Surgical resection revealed that the lesion in the lower body was a poorly cohesive carcinoma invading the submucosa with vascular involvement, whereas the lesion in the angle was an intramucosal differentiated adenocarcinoma. A review of previous studies of gastric cancer with H. pylori-negative AIG suggested that patients with histologically and serologically advanced gastritis are at high risk for carcinogenesis. Even in H. pylori-negative cases, severe gastric mucosal atrophy in AIG cases may indicate a carcinogenic risk; therefore, surveillance for gastric cancer is especially recommended for these cases. Large cohort studies on the association between H. pylori-negative AIG and gastric cancer are warranted.

A Case of Pernicious Anemia with Concurrent Beta-Thalassemia Minor.

Vitamin B12 is essential for various bodily functions, and its deficiency may cause hematological manifestations. We report a case of a previously healthy 65-year-old female who was admitted to our hospital with reduced sense of taste and painful tongue. The serum level of vitamin B12 was decreased. However, her complete blood count did not show any evidence of macrocytosis, instead, her mean corpuscular volume was low. Gene sequencing indicated an ß-thalassemia minor and that probably masked the megaloblastic features of vitamin B12 deficiency.

Unveiling early stage autoimmune gastritis: novel endoscopic insights from two case reports.

The predominant characteristic of autoimmune gastritis (AIG) is corpus-dominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are needed on the endoscopic features of the early stage. In this report, we present two cases of early-stage AIG in which endoscopic examinations showed no atrophy of the gastric mucosa but displayed a transition of collecting venules from a regular to an irregular arrangement. In addition, yellowish-white cobblestone-like elevations were observed in the fundic gland region. Histologically, the observed manifestations included pseudohypertrophy and protrusion of parietal cells into the lumen, possibly along with hyperplasia of G cells, lymphocytic infiltration and potentially pseudopyloric gland metaplasia. Serologically, the anti-parietal cell antibody returned positive results, whereas the anti-intrinsic factor antibody yielded negative results. In this study, we summarized some endoscopic features of two patients, aiming to provide clues for endoscopists to detect early-stage AIG.

Coexistence of Guillain-Barré Syndrome and Subacute Combined Degeneration of the Spinal Cord Due to Autoimmune Gastritis: A Case Report and Literature Review.

Guillain-Barré syndrome (GBS) and autoimmune gastritis (AIG) are both autoimmune diseases (ADs) that have a low prevalence in China. Both conditions involve the immune system mistakenly attacking the body's own tissues. GBS primarily affects the peripheral nervous system, leading to muscle weakness and paralysis, while AIG targets the stomach lining, causing inflammation and reduced absorption of vital nutrients. Subacute combined degeneration (SCD) of the spinal cord is the most common neurological manifestation of vitamin B12 deficiency. As of yet, there have been no reported cases of patients with GBS and complications of AIG including SCD. We report a case of a 54-year-old male patient who had been experiencing progressive numbness and weakness in his extremities, burning and tingling sensations, a cotton-stepping sensation, and difficulty walking for three weeks. He was admitted to the hospital and underwent an extensive medical workup. Magnetic resonance imaging (MRI) of the cervical spine cord showed abnormal spinal cord signal intensity consistent with typical manifestations of vitamin B12 deficiency. Gastric endoscopy revealed local atrophy of the gastric corpus, and gastric tissue biopsy indicated atrophic gastritis with intestinal metaplasia, consistent with a diagnosis of AIG. Lumbar puncture of cerebrospinal fluid (CSF) results showed albumincytological dissociation, further confirming the diagnosis of GBS. He was treated with intravenous immunoglobulin and methylcobalamin therapy for these conditions and showed significant clinical improvement upon discharge.

Characteristics of Early Gastric Cancer in a Patient with a History of Helicobacter pylori Infection and No History of Eradication Therapy.

Objective The characteristics of gastric cancer in patients with atrophic mucosa and no apparent history of Helicobacter pylori eradication have not been thoroughly investigated. Therefore, this study examined the clinicopathological characteristics of gastric cancer in these patients. Methods We retrospectively examined the endoscopic and pathological characteristics of gastric cancer in patients who underwent endoscopic submucosal dissection. Patients or Materials We divided the patients into 2 groups: those with gastric atrophy and no history of eradication (group A; n =102) and those with a history of eradication (group B; n =161). In group A, patients were further divided into mild atrophy (group C) and severe atrophy (group D) groups, while group B was further divided into those who underwent eradication treatment >5 years ago (group E) and those who underwent eradication 1-5 years ago (group F). Results Group A comprised significantly older individuals (75±8.0 vs. 71±7.5 years old, p <0.001) with a higher frequency of elevated gastric cancer than group B (32.4% vs. 17.4%, p =0.006). Compared with group E, group A was older and had a greater incidence of elevated gastric cancer. The incidence of gastric cancer in the U or M region was lower in group C than in group D. Conclusion Gastric cancer in patients with gastric atrophy and no history of eradication was associated with an older age and higher frequency of elevated-type morphology than in those with a history of eradication.

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.

Chronic Atrophic Autoimmune Gastritis: The Evolving Role of Vitamin D.

Vitamin D possesses a crucial role in preserving bone health, modulating the immune system responses, and supporting various physiological functions throughout the body. Chronic atrophic autoimmune gastritis (CAAG) constitutes an autoimmune condition marked by inflammation and damage to the stomach cells, often resulting in a decreased ability to absorb certain nutrients, including vitamin B12 and iron. Although, vitamin D is not directly affected by this condition, the sufficiency of this micronutrient seems to have important implications for overall health and management of the disease. The aim of the current review was to assess the incidence and related features of vitamin D deficiency in patients with CAAG and to elucidate the complex regulatory role of this nutrient, in an effort to improve patient outcomes. Vitamin D greatly contributes to the regulation of the immune system. In patients with CAAG, the immune system attacks the stomach lining; thus, the maintenance of a healthy and balanced immune response is important. In autoimmune conditions such as CAAG, where inflammation plays a decisive role in disease progression, vitamin D could potentially exert a role in managing and controlling the associated symptoms. Adequate vitamin D levels may help in regulating the immune response and reducing inflammation. In addition, patients with CAAG are at risk of nutrient deficiencies, including vitamin B12 and iron, which can lead to anemia and bone health issues. As vitamin D is critical for calcium absorption and bone health, assurance of sufficient levels of this micronutrient can be beneficial in preventing or mitigating bone-related complications. In conclusion, regular monitoring of vitamin D levels, among other nutrients, and appropriate supplementation, when necessary, can help improve overall health and well-being in these patients.

Clinical Characteristics of Patients With Previous Helicobacter pylori Infection-Induced Atrophic Gastritis.

AIMS: Patients with atrophic gastritis unrelated to autoimmune gastritis (AIG) and without active Helicobacter pylori (H.pylori) infection or previous eradication therapy are considered to have previous Helicobacter pylori infection-induced atrophic gastritis (PHIG). This study aimed to clarify the clinical characteristics of patients with PHIG. METHODS: Consecutive patients who underwent upper gastrointestinal endoscopy during the study period were enrolled in the study. Pepsinogen and gastrin levels, H. pylori serology, and endoscopic atrophic grade were assessed. Patients were divided into five groups based on their H. pylori status and disease history (PHIG, without H. pylori infection, with active H. pylori infection, with successful H. pylori eradication, and AIG). Their gastric cancer risk status was classified according to the ABC method of serological gastric cancer screening. RESULTS: Of 536 consecutive patients who underwent upper gastrointestinal endoscopy during the study period, 318 were included (31 with PHIG, 77 without H. pylori infection, 101 with active H. pylori infection, 80 with successful H. pylori eradication, and 29 with AIG). Of the 31 patients with PHIG, 21 (68%) were H. pylori-seronegative, and 20 (65%) were classified as group A (normal pepsinogen, H. pylori-seronegative). Patients with PHIG accounted for 90.1% of the patients at high risk for gastric cancer misclassified as group A. The pepsinogen and H. pylori serological profiles of patients with PHIG were similar to those of patients with successful H. pylori eradication more than six years previously. A receiver-operating characteristic curve (ROC) analysis that included 13 patients with AIG and without active H. pylori infection and no previous eradication therapy and 31 patients with PHIG revealed that an endoscopic atrophy grade of O-III or greater according to the Kimura-Takemoto classification can predict AIG. CONCLUSIONS: Two-thirds of the patients with PHIG were misclassified as being at low risk (group A) according to the ABC method, suggesting that endoscopy is necessary for group A patients. The results of the serological evaluation of PHIG indicated that patients with PHIG may have experienced spontaneous H. pylori eradication, possibly because of the use of antibiotics for other conditions. Autoimmune gastritis should be considered in the presence of grade 0-III or greater gastric mucosal atrophy in patients with suspected PHIG, even if the autoantibody and histological findings are not available.

Clinicopathological Features of Early Gastric Cancer Complicated by Autoimmune Gastritis.

INTRODUCTION: In the post-Helicobacter pylori era, autoimmune gastritis (AIG) is attracting increasing attention as an origin of gastric cancer. Here, we performed clinicopathological examination of gastric cancer complicating AIG treated in our hospital. METHODS: Eighty-six early gastric cancer lesions complicating AIG in 50 patients were treated by endoscopic submucosal dissection (ESD) at our hospital in 2008-2022. Their clinicopathological characteristics were compared with those of a control group comprising 2,978 early gastric cancer lesions (excluding lesions in the remnant stomach after surgery) in 2,278 patients treated by ESD during the same period. RESULTS: Mean age was significantly higher in the AIG group than in the control group (74.7 years vs. 70.9 years; p < 0.01). In the respective groups, the occurrence rate of synchronous/metachronous lesions was 38.0% and 20.4% (p < 0.01), the ratio of longitudinal cancer locations (upper/middle/lower third [U/M/L]) was 27/32/27 and 518/993/1,467 (p < 0.01), the ratio of circumferential cancer locations (lesser curvature/greater curvature/anterior wall/posterior wall) was 25/31/12/18 and 1,259/587/475/657 (p < 0.01), the ratio of major macroscopic types (I/IIa/IIb/IIc) was 13/38/5/30 and 65/881/220/1,812 (p < 0.01). The rates of multiple gastric cancer and cancers in the U region, at the greater curvature, and of protruding types were significantly higher in the AIG group. CONCLUSION: The occurrence rate of multiple gastric cancer was significantly higher in gastric cancer complicating AIG (approximately 40%), and compared with the control group, the proportions of cancers at the U region, at the greater curvature, and of protruding types were significantly higher.

Pernicious Anemia Unveiled: Unusual Hemolytic Complications and Clinical Implications.

Pernicious anemia (PA) is an autoimmune condition resulting in impaired vitamin B12 absorption that commonly presents with gastritis and neurological symptoms. In rare cases, associated vitamin B12 deficiency can contribute to significant red blood cell lysis, and patients can present with PA-induced pseudo-thrombotic microangiopathy (TMA) hemolytic anemia. This case describes a 59-year-old male presenting with a two-week history of gastrointestinal pain with bleeding who had anemia and hemodynamic instability on initial evaluation. After the endoscopy/colonoscopy did not reveal any active sources of bleeding and packed red blood cells failed to stabilize the patient, it was found that he had low serum B12 with anti-intrinsic factor and anti-parietal cell antibodies. A coordinated clinical approach, including parenteral cyanocobalamin and daily oral folic acid supplementation, stabilized the patient, highlighting the importance of distinguishing PA-induced pseudo-TMA from true TMA hemolytic anemia.

Gastric Carcinoma in Autoimmune Gastritis: A Histopathologic and Molecular Study.

Patients with autoimmune gastritis (AIG) have a 13-fold risk of developing type-1 neuroendocrine tumors, whereas the risk for gastric adenocarcinoma is still uncertain. Here we describe the clinicopathologic and molecular features of a series of gastric carcinomas (GC) arising in the context of AIG. A total of 26 AIG-associated GC specimens were collected from 4 Italian Institutions. Immunohistochemistry for MUC1, MUC2, MUC5AC, MUC6, CDX2, HER2, PD-L1, CLDN18, mismatch repair (MMR) proteins, and p53 and EBV-encoded RNA (EBER) in situ hybridization were performed. Histologic and immunohistochemical features were jointly reviewed by 5 expert gastrointestinal pathologists. Next-generation sequencing analysis (TrueSight Oncology 500, Illumina) of 523 cancer-related genes was performed on 19 cases. Most tumors were diagnosed as pT1 (52%) and they were located in the corpus/fundus (58%) and associated with operative link for gastritis assessment stage II gastritis (80.8%), absence of parietal cells, complete intestinal metaplasia, and enterochromaffin-like-cell micronodular hyperplasia. Only 4 (15.4%) GCs were diagnosed during follow-up for AIG. The following histotypes were identified: 20 (77%) adenocarcinomas; 3 (11%) mixed neuroendocrine-non-neuroendocrine neoplasms, and 2 (8%) high-grade solid adenocarcinomas with focal neuroendocrine component, 1 (4%) adenocarcinoma with an amphicrine component. Overall, 7 cases (27%) showed MMR deficiency, 3 (12%) were positive (score 3+) for HER2, 6 (23%) were CLDN18 positive, and 11 (42%) had PD-L1 combined positive score ≥ 10. EBER was negative in all cases. Molecular analysis revealed 5/19 (26%) microsatellite instability (MSI) cases and 7 (37%) tumor mutational burden (TMB) high. The most frequently altered genes were TP53 (8/19, 42%), RNF43 (7/19, 37%), ERBB2 (7/19, 37% [2 amplified and 5 mutated cases]), ARID1A (6/19, 32%), and PIK3CA (4/19, 21%). In summary, AIG-associated GCs are often diagnosed at low stage in patients with longstanding misrecognized severe AIG; they often display a neuroendocrine component or differentiation, have relatively higher rates of MMR deficiency, and TMB high.

When rare diseases crisscross within the same patient: von Hippel-Lindau and type 1 gastric neuroendocrine tumor.

Von-Hippel-Lindau (VHL) is a genetic multisystem disorder characterized by visceral cysts and benign and malignant tumors in various organs. Herein, we present the case of a 23-year-old woman with VHL presenting with multiple gastric neuroendocrine neoplasms (gNENs) type 1 in the context of chronic autoimmune gastritis (CAG). Although gNENs are not acknowledged as a typical entity in VHL patients, in the present case, gNENs were composed of neoplastic cells with clear cytoplasm usually seen in tumors related to VHL disease. We additionally performed a literature review on the presence of neuroendocrine clear cell tumors and report on further cases of clear cell NENs. The present case illustrates that clear-cell transformation in gNENs may be due to the dual genetic background of the patient; the real oncogenic stimulus may be more closely related to CAG than to VHL disease accompanied by an interplay between neoplastic and autoimmune processes. Therefore, close monitoring of patients with clear cell NENs appears to be important before excluding VHL disease, even in the context of phenotypically unrelated diseases.

Utilidad de los anticuerpos anti-células parietales gástricas y anti-factor intrínseco en el estudio de la deficiencia de vitamina B12 asociada a gastritis autoinmune y anemia perniciosa / Usefulness of anti-gastric parietal cell and anti-intrinsic factor antibodies in the study of vitamin B12 deficiency associated with autoimmune gastritis and pernicious anemia / Utilidade de anticorpos anti-células parietais gástricas e anti-fator intrínseco no estudo da deficiência de vitamina B12 associada à gastrite autoimune e à anemia perniciosa

Resumen La gastritis autoinmune (GAI) es una afección inflamatoria progresiva de la mucosa oxíntica caracterizada por la destrucción de células parietales, pérdida de factor intrínseco, malabsorción de vitamina B12 (cobalamina), hierro y otros micronutrientes y puede progresar hacia un estado avanzado de anemia megaloblástica conocida como anemia perniciosa (AP). El objetivo de este estudio fue determinar la deficiencia de vitamina B12 debida a malabsorción utilizando la detección de anticuerpos anti-células parietales gástricas (ACPG) y anti-factor intrínseco (AFI). Se analizaron 2050 sueros de pacientes con un inmunoanálisis quimioluminiscente para vitamina B12 total y 2,8% de éstos con las pruebas de inmunofluorescencia indirecta para ACPG y enzimoinmunoanálisis para AFI. La deficiencia de vitamina B12 (<200 ng/mL) fue del 13,1%. En la detección de anticuerpos se encontró: 2 doble positivos ACPG/AFI, 17 simple positivos ACPG y 4 simple positivos AFI. Todas las muestras ACPG y/o AFI positivas tuvieron valores de vitamina B12 total <200 ng/mL. En 5 pacientes con ACPG positivos se diagnosticó gastritis crónica confirmada por biopsia. En los 6 pacientes AFI positivos se realizó el diagnóstico de AP y en 2 de ellos se confirmó por histopatología. La positividad de ACPG y/o AFI permitió la clasificación de pacientes con sospecha de GAI en candidatos para la examinación histológica y la aplicación de esquemas terapéuticos adecuados. Se destaca la importancia de las pruebas de laboratorio como parte de una estrategia de diagnóstico temprano y vigilancia endoscópica, para evitar las manifestaciones relacionadas con la deficiencia de hierro y vitamina B12 y las complicaciones de la enfermedad avanzada.

Abstract Autoimmune gastritis (AIG) is a progressive inflammatory condition of the oxyntic mucosa, characterised by gastric parietal cell destruction, loss of intrinsic factor, and malabsorption of vitamin B12 (cobalamin), iron and other micronutrients; conditioning progress to a state of megaloblastic anemia known as pernicious anemia (PA). The aim of this study was to determine vitamin B12 deficiency due to malabsorption utilizing anti-parietal cell (APCA) and anti-intrinsic factor (IFA) antibodies detection. 2050 patient serum samples were analised by chemiluminescent immunoassay for vitamin B12. A total of 2.8% of them were tested for APCA by indirect immunofluorescence and for IFA by enzyme immunoessay. Vitamin B12 deficiency (<200 ng/mL) was 13.1%. Regarding antibody detection: 2 APCA/IFA double positives, 17 APCA simple positives and 4 IFA simple positives were found. APCA and/or IFA positive samples had total vitamin B12 values <200 ng/mL. Chronic gastritis confirmed by biopsy was diagnosed in 5 patients with positive ACPG antibodies. All 6 IFA positive patients were diagnosed with PA, while 2 of them also received histopatologic confirmation. APCA and/or IFA confirmation allowed for the classification of patients with suspicion of AIG as possible candidates for histologic examination and application of appropriate therapeutic schemes. Importance of laboratory testing is to be noted; as part of a strategy that enables early diagnosis and adequate endoscopic surveillance, to avoid manifestations related to iron and vitamin B12 deficiency and the complications of advanced disease.

Resumo A gastrite autoimune (GAI) é uma doença inflamatória progressiva da mucosa oxíntica, caracterizada pela destruição das células parietais gástricas, perda do fator intrínseco, má absorção de vitamina B12 (cobalamina), ferro e outros micronutrientes pode progredir para um estado avançado de anemia megaloblástica conhecida como anemia perniciosa (AP). O objetivo deste estudo foi determinar a deficiência de vitamina B12 por má absorção usando a detecção de anticorpos anti-células parietais gástricas (ACPG) e anti-fator intrínseco (AFI). Foram analisados 2050 soros de pacientes com um imunoensaio quimioluminiscente para vitamina B12 total, 2,8% deles com testes de imunofluorescência indireta para ACPG e enzimaimunoensaio para AFI. A deficiência de vitamina B12 (<200 ng/mL) foi de 13,1%. Na detecção de anticorpos foram encontrados: 2 duplo positivos ACPG/AFI, 17 simples positivos ACPG e 4 simples positivos AFI. Todas as amostras ACPG e/ou AFI positivas apresentaram valores de vitamina B12 total <200 ng/mL. Gastrite crônica confirmada por biópsia foi diagnosticada em 5 pacientes positivos para ACPG. Nos 6 pacientes AFI positivos o diagnóstico de AP foi feito e em 2 deles foi confirmado por histopatologia. A positividade para ACPG e/ou AFI permitiu a classificação de pacientes com suspeita de GAI em candidatos para exame histológico e a aplicação de esquemas terapêuticos adequados. Destaca-se a importancia dos testes laboratoriais, como parte de uma estratégia de diagnóstico precoce e vigilância endoscópica, para evitar manifestações relacionadas à deficiência de ferro e vitamina B12 e complicações da doença avançada.

Emergency Endoscopic Hemostasis Using the Endoscopic Mucosal Resection Technique for Severe Bleeding From Early Gastric Cancer: A Case Report.

Bleeding from gastric cancer may lead to severe anemia and hypovolemic shock, and can be a life-threatening condition in affected patients; thus, achieving hemostasis is essential to improving their clinical course. While endoscopic hemostasis is recommended as the hemostatic modality of first choice, endoscopic hemostasis involving the endoscopic mucosal resection (EMR) technique is also being used, though under-reported. An 85-year-old man diagnosed with bleeding from gastric cancer was raced to our hospital for hemostasis. Emergency esophagogastroduodenoscopy (EGD) revealed a 45 mm-sized elevated lesion involving the coagula due to dripping bleeding from the surface of the posterior wall of the gastric lower body. EMR was performed without any technical difficulty, and hemostasis was achieved immediately. The patient was discharged without rebleeding. This case appears to support the usefulness of EMR as an emergency endoscopic hemostatic modality for severe bleeding from early gastric cancer.