Characteristic endoscopic findings in early-stage autoimmune gastritis.

Background and study aims Until recently, autoimmune gastritis (AIG) was usually diagnosed at late stages based on typical endoscopic findings, including corpus-dominant advanced atrophy. Early-stage AIG prior to complete gastric atrophy had rarely been diagnosed due to a lack of knowledge about its endoscopic characteristics. The present study sought to identify the endoscopic characteristics of early-stage AIG, enabling its early diagnosis. Patients and methods The clinical and endoscopic findings of 12 patients diagnosed with early-stage AIG between 2016 and 2021 were retrospectively evaluated. Patients were included if they were: (1) positive for serum anti-parietal cell antibody; (2) diagnosed with histological early-stage AIG; and (3) endoscopically positive for folds on the greater curvature of the gastric corpus. Results Two characteristic endoscopic findings of early-stage AIG were identified: longitudinal alignment of pseudopolyps (i.e., a bamboo joint-like appearance) and swelling of gastric areas with erythema (i.e., a salmon roe-like appearance). Conclusions Endoscopic findings characteristic of early-stage AIG include a bamboo joint-like appearance and a salmon roe-like appearance. Studies in large numbers of patients with long-term follow-up are needed to confirm these findings.

Marked intestinal trans-differentiation by autoimmune gastritis along with ectopic pancreatic and pulmonary trans-differentiation.

BACKGROUND: Autoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms. METHODS: A comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs. Gastric cancer cell lines were cultured under acidic (pH 6.5) conditions to evaluate changes in gene expression. RESULTS: Gastric mucosa with AIG had a unique gene expression profile compared with that with HPG and normal mucosa, such as extensively low expression of ATP4A and high expression of GAST and PAPPA2, which are involved in neuroendocrine tumorigenesis. Additionally, the mucosa with AIG and HPG showed the downregulation of stomach-specific genes and upregulation of small intestine-specific genes; however, intestinal trans-differentiation was much more prominent in AIG samples, likely in a CDX-dependent manner. Furthermore, AIG induced ectopic expression of pancreatic digestion-related genes, PNLIP, CEL, CTRB1, and CTRC; and a master regulator gene of the lung, NKX2-1/TTF1 with alveolar fluid secretion-related genes, SFTPB and SFTPC. Mechanistically, acidic conditions led to the downregulation of master regulator and stemness control genes of small intestine, suggesting that increased environmental pH may cause abnormal intestinal differentiation in the stomach. CONCLUSIONS: AIG induces diverse trans-differentiation in the gastric mucosa, characterized by the transactivation of genes specific to the small intestine, pancreas, and lung. Increased environmental pH owing to AIG may cause abnormal differentiation of the gastric mucosa.

Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential.

BACKGROUND: Autoimmune gastritis (AIG) is a chronic inflammatory condition in gastric mucosa and is associated with increased cancer risk, though not as high as that by Helicobacter pylori (H. pylori)-associated gastritis (HPG). Although aberrant DNA methylation is induced by HPG and the level correlates with the risk of gastric cancer, DNA methylation induction by AIG is unknown. METHODS: Gastric mucosa samples from the corpus were collected from 12 people with AIG without H. pylori infection, 10 people with HPG, and eight healthy volunteers. Genome-wide DNA methylation analysis was conducted using Infinium Methylation EPIC array. Gene expression was analyzed by quantitative RT-PCR. RESULTS: The AIG samples had extensive aberrant DNA methylation but presented unique methylation profiles against the HPG samples after correction of leucocyte fractions. Comparison between the AIG and HPG samples showed that AIG induced methylation, but less than HPG, in overall CpG sites and also in promoter CpG islands. Promoter CpG islands of tumor-suppressor genes in the pathway of cell cycle, cell adhesion, p53, and WNT were highly methylated in the AIG samples, but more so in the HPG samples. The expression levels of IL1B and IL8, secreted by macrophage, were significantly lower in the AIG samples than in the HPG samples, suggesting that a difference in inflammatory response affected the degree and patterns of aberrant DNA methylation. CONCLUSIONS: AIG induced aberrant DNA methylation in gastric mucosa. However, the degree of DNA methylation was less than that by HPG, which reflected carcinogenic risk.

Clinicopathological characteristics of early gastric cancer associated with autoimmune gastritis.

BACKGROUND: Autoimmune gastritis is known to be associated with neoplastic lesions but the relationship between autoimmunity and tumorigenesis have not been sufficiently clarified. The aim of this study is to assess the clinicopathological characteristics of gastric cancer cases associated with autoimmune gastritis. METHODS: A total of 24 patients diagnosed as early gastric cancer with autoimmune gastritis were registered. Chart reviews with the data including age, gender, state of Helicobacter pylori infection, comorbidity, and concomitant gastric diseases were conducted. As for the characteristics of gastric cancer, location, size, morphological type, histopathology, invasion depth, and the presence of metachronous or simultaneous lesion were assessed. These data from autoimmune gastritis group were compared with those from 301 patients of early gastric cancer as a control group. RESULTS: The gastric cancer associated with autoimmune gastritis was located in the upper, middle, and lower parts in 28.1%, 53.1%, and 18.8%, respectively. The morphological types are as follows: 0-I, 9.4%; 0-IIa, 28.1%; 0-IIb, 15.6%; 0-IIc, 46.9%; and 0-III, 0.0%. The mean tumor size was 21.8 mm. While 90.6% were confined to the mucosa, 9.4% showed submucosal invasion. The histological classifications are as follows: tub1, 50.0%; tub2, 15.6%; pap, 21.9%; sig, 9.4%; and por, 3.1%. More numbers of female, protruded types, larger tumor size, papillary tumor, and that in the upper location were observed in autoimmune gastritis group compared to control group. CONCLUSION: Early gastric cancer associated with autoimmune gastritis demonstrated different characteristics from those without autoimmune gastritis including variety of tumor morphologies and histological types with female dominancy.

Endoscopic and Upper Gastrointestinal Barium X-ray Radiography Images of Early-stage Autoimmune Gastritis: A Report of Two Cases.

We herein report two patients with early-stage autoimmune gastritis who did not exhibit complete atrophy. Endoscopic examinations showed no manifestations of severe atrophic gastritis, but revealed a mosaic pattern with slight swelling of the areae gastricae restricted to the corpus in both patients. In the patient in case 2, upper gastrointestinal barium X-ray radiography revealed a slightly protruded irregular areae gastricae throughout the gastric body, except for in the antrum. Our findings emphasize the need for clinicians to recognize that autoimmune gastritis might be present in the absence of severe atrophic gastritis; this can aid in the identification of the early stages of autoimmune gastritis.

Diagnostic Accuracy of H. pylori Status by Conventional Endoscopy: Time-Trend Change After Eradication and Impact of Endoscopic Image Quality.

AIM: To assess the time trend of diagnostic accuracy of pre- and post-eradication H. pylori status and interobserver agreement of gastric atrophy grading. METHODS: A series 100 of conventional endoscopic image sets taken from subjects undergoing gastric cancer screening at a polyclinic were evaluated by 5 experienced assessors. Each assessor independently examined endoscopic findings according to the Kyoto classification and then determined the H. pylori status (never, current, or past infected). Gastric atrophy was assessed according to the Kimura-Takemoto classification and classified into 3 grades (none/mild, moderate, or severe). The image series that ≥3 assessors considered to have good quality were arbitrarily defined as high-quality image (HQI) series, and the rest were defined as low-quality image (LQI) series. RESULTS: The overall diagnostic accuracy of H. pylori status was 83.0%. It was lowest in subjects with current infection (54%), gradually increased at 1 year (79%, P < 0.001) and 3 years (94.0%, P = 0.002), but then did not significantly change at 5 years (91.0%, P = 0.420) after eradication. The rate of LQI series was 28%. The overall diagnostic accuracy of H. pylori status dropped from 88.9% to 67.9% (P < 0.001), and the mean kappa value on gastric atrophy grading dropped from 0.730 to 0.580 (P = 0.002) in the HQI and LQI series, respectively. CONCLUSIONS: Diagnostic accuracy of H. pylori status increased over time after eradication. LQI series badly affected the diagnostic accuracy of H. pylori status and the level of agreement when grading gastric atrophy.

Multicenter study of autoimmune gastritis in Japan: Clinical and endoscopic characteristics.

BACKGROUND AND AIM: In Japan, the prevalence of autoimmune gastritis (AIG) is assumed to be very low. With the recent rapid decrease in Helicobacter pylori (Hp) prevalence, reports on AIG are increasing. This multicenter registry study aimed to clarify the characteristics of AIG, especially its endoscopic appearance. METHODS: A total of 245 patients with AIG from 11 institutions in Japan from January 2010 to October 2016 were included, and their clinical and endoscopic findings were evaluated. RESULTS: Mean age was 67.2 ± 11.4 years, and 63.7% of the participants were women. The most common approach to diagnose AIG was endoscopic examination. Repeated incorrect treatment for Hp infection, due to a false-positive result in 13 C-urea breath test, ranked third among the basis for diagnosis of AIG. Associated gastric lesions were type 1 neuroendocrine tumor (11.4%), adenocarcinoma (9.8%), and hyperplastic polyps (21.1%). Corpus pan-atrophy was the most common appearance (90.1%); however, remnant oxyntic mucosa was found in 31.5% of the patients (flat, localized type, 48.6%). Sticky adherent dense mucus and scattered minute whitish protrusions were also observed in approximately 30% of the patients. Despite the prevailing presumption of the antral mucosa remaining normal, 42.3% of the patients presented with various extents of atrophy, and patchy redness and circular wrinkle-like patterns were both observed in approximately 20% of the patients. CONCLUSIONS: The present study showed some prominent clinical characteristics and endoscopic findings of AIG. We believe that our study will facilitate the diagnosis of potential AIG.

Glutamate Promotes Contraction of the Rat Ductus Arteriosus.

BACKGROUND: Extremely preterm infants frequently have patent ductus arteriosus (PDA). Recent recommendations include immediately beginning amino acid supplementation in extremely preterm infants. However, the effect of amino acids on closure of the ductus arteriosus (DA) remains unknown.Methods and Results:Aminogram results in human neonates at day 2 revealed that the plasma glutamate concentration was significantly lower in extremely preterm infants (<28 weeks' gestation) with PDA than in those without PDA and relatively mature preterm infants (28-29 weeks gestation). To investigate the effect of glutamate on DA closure, glutamate receptor expression in fetal rats was examined and it was found that the glutamate inotropic receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type subunit 1 (GluR1), mRNA was highly expressed in the DA compared to the aorta on gestational day 19 (preterm) and gestational day 21 (term). GluR1 proteins were co-localized with tyrosine hydroxylase-positive autonomic nerve terminals in the rat and human DA. Intraperitoneal administration of glutamate increased noradrenaline production in the rat DA. A whole-body freezing method demonstrated that glutamate administration induced DA contraction in both preterm (gestational day 20) and term rat fetuses. Glutamate-induced DA contraction was attenuated by the calcium-sensitive GluR receptor antagonist, NASPM, or the adrenergic receptor α1 blocker, prazosin. CONCLUSIONS: These data suggest that glutamate induces DA contraction through GluR-mediated noradrenaline production. Supplementation of glutamate might help to prevent PDA in extremely preterm infants. (Circ J 2016; 80: 2388-2396).

Interobserver and intraobserver agreement for gastric mucosa atrophy.

BACKGROUND: The grade of gastric mucosa atrophy caused by Helicobacter pylori (H. pylori) infection is closely associated with the risk of gastric cancer, especially of the intestinal type. Interobserver and intraobserver agreement for endoscopic gastric mucosa atrophy in subjects with H. pylori-uninfected, currently infected and past infected was investigated. METHODS: Endoscopic images of 91 patients, 34 images per patient, were assessed. The assessors were 4 endoscopist groups: Japanese and Vietnamese experienced (≥7, ≤ 15 year experience with endoscopy) and Japanese and Vietnamese beginner (≤ 3 year experience) groups. Each group comprised 3 endoscopists. The grades of atrophy were classified as 3: none to mild (C-0 and C-1), moderate (C-2 and C-3), and severe (O-1, O-2, and O-3) using the Kimura-Takemoto Classification. After a period of 2 weeks, images of all patients were reevaluated by the investigators. Interobserver and intraobserver agreement was calculated by kappa statistics. RESULTS: The kappa values for the interobserver agreement in the groups of Japanese and Vietnamese experienced, and Japanese and Vietnamese beginner were 0.474, 0.408, 0.291, and 0.373, respectively. The kappa value of intraobsever agreement in the Japanese and Vietnamese experienced endoscoists ranged from 0.585 to 0.871. On the other hand, the value in the beginner endoscopists ranged wider than that in experienced endoscopists, from 0.264 to 0.866. CONCLUSIONS: Our results indicated that, although intraobserver agreement for gastric mucosa atrophy was good to excellent, interobserver agreement was moderate in experienced endoscopists. This suggests that better guidelines and firm criteria may be needed to properly diagnose and grade gastric atrophy.

Decreased serum osmolality promotes ductus arteriosus constriction.

AIMS: At birth, dynamic changes occur in serum components and haemodynamics, such as closure of the ductus arteriosus (DA). A previous study demonstrated that, in full-term human neonates, serum osmolality decreased transiently after birth, but recovered over the next few days. However, the significance of this transient decrease in osmolality has never been addressed. The objective of the present study was to examine the role of changes in serum osmolality after birth in DA closure. METHODS AND RESULTS: We found that rats exhibited a similar transient hypoosmolality after birth. Hypotonic stimulation induced constriction of DA rings and increased Ca(2+) transient in DA smooth muscle cells, but not in the aorta. The hypoosmotic sensor transient receptor potential melastatin 3 (TRPM3) was highly expressed in the rat DA, and TRPM3 silencing abolished the Ca(2+) response to hypoosmolality. Pregnenolone sulfate stimulation of TRPM3 induced rat DA constriction ex vivo and in vivo. Furthermore, hypertonic fluid injection impaired rat DA closure. In humans, neonatal serum hypoosmolality was observed in relatively mature preterm infants (≥28 weeks). In extremely preterm infants (<28 weeks), however, this hypoosmolality was absent. Instead, a rapid increase in osmolality occurred thereafter. Such an increase was greater, in particular, among patent DA (PDA) patients. CONCLUSIONS: A transient decrease in serum osmolality may promote DA closure during the first few days of life. Adjusting serum osmolality to proper levels might help to prevent the onset of PDA, improving the therapeutic outcome in extremely preterm infants.

Twig tea impaction in the colon causing abdominal pain.

We describe a case of lower abdominal pain caused by a twig tea impaction at the rectosigmoid junction after inadvertent ingestion. The foreign body was detected and successfully dislodged from the colonic wall with grasping forceps during colonoscopy. The post-procedural course was uneventful, and the patient was discharged 10 days after the removal. Colonic injury, including perforation due to foreign body ingestion, must be considered in patients presenting with unexplained symptoms and findings, even when they do not recall any foreign body ingestion.

Evaluation of serum amylase and gabexate mesilate with endoscopic papillary balloon dilatation.

Gabexate mesilate (GM) relaxes the papilla of Vater in addition to inhibiting the several proteases. We evaluated whether prophylactic administration of GM would prevent the occurrence of acute pancreatitis in endoscopic papillary balloon dilation (EPBD). Nineteen patients with common bile duct stones were separated into two groups according to the admission year. The group A has been administered GM intravenously at 2mg/kg/hr after EPBD till six hours later, and the group B has been administered GM before fifteen minutes of EPBD till six hours later. The mean value of sphincter of Oddi (SO) basal and peak pressure in the group B was significantly lower than that in the group A, moreover the mean value of the pancreatic pressure in the group B was significantly lower than that in the group A. However two cases had mild acute pancreatitis in the group B. GM loosened SO and pancreatic duct pressure by direct stimulation of SO, although it could not have enough effect to prevent the acute pancreatitis in EPBD.

Clinicopathological evaluation of biological behavior of submucosal invasive gastric carcinomas: relationship among lymph node metastasis, mucin phenotype and proliferative activity.

BACKGROUND: Gastric carcinomas have been classified into the differentiated and undifferentiated type, on the basis of its tendency to gland formation. As a result of recent advances in mucin histochemistry, mucin phenotypes of gastric carcinomas have been investigated. However, no consensus on the evaluation of the grade of malignancy of early gastric carcinomas regarding mucin phenotype expression has developed. To address this issue, we evaluated the lymph node metastasis rate and proliferative activity of a submucosal invasive (sm) gastric carcinoma according to mucin phenotype expression. METHODS: In resected surgical specimens from 108 patients with a single sm gastric carcinoma, the association between clinicopathological factors and lymph node metastasis was evaluated. In all cases, immunohistochemical staining with human gastric mucin, Muc-2, and CD10 and mucin histochemical staining by paradoxical concanavalin A staining were performed. The mucin phenotypes were classified into gastric-type (G-type), intestinal-type (I-type), mixed gastric and intestinal type (M-type), or a lack of mucin (LOM), using these as markers. To evaluate the cell proliferative activity of the gastric carcinoma, proliferating cell nuclear antigen (PCNA) staining was also performed. RESULTS: The rate of lymph node metastasis was higher for G-type sm carcinomas. A multivariate analysis showed that the G-type and lymphatic invasion were independent factors of lymph node metastasis. However, the PCNA-labeling index (PCNA-LI) was low for G-type carcinomas irrespective of the presence or absence of lymph node metastasis. In I-type carcinomas, PCNA-LI was significantly higher in cases that were positive for lymph node metastasis than in negative cases. CONCLUSION: G-type and lymphatic invasion are independent risk factors for lymph node metastasis of an sm gastric carcinoma, and proliferative activity may be a significant parameter for lymph node metastasis in cases with I-type carcinomas.

Relationship between lymph node metastasis and E-cadherin expression in submucosal invasive gastric carcinomas with gastric-phenotype.

BACKGROUND: Recent advances in immunohistochemical staining have led to the proposition of a classification of gastric carcinomas based on cellular phenotypes, and the degree of biological malignancy of gastric-phenotype carcinomas has attracted particular attention. SUBJECTS AND METHODS: One hundred and seven submucosal (SM) invasive carcinomas encountered in our center were examined for their histological type, cellular phenotype, and E-cadherin expression status to clarify their relationships with lymph node metastasis. RESULTS: Eleven (10.3%) of 107 SM gastric carcinomas were lymph node metastasis-positive. Gastric-phenotype carcinomas accounted for 20.6%, with a lymph node metastasis rate of 27.3% (6/22), which was significantly higher (p<0.05) than those of intestinal-phenotype carcinomas (5.9%) and mixed-phenotype carcinomas (2.9%). In terms of E-cadherin expression, only carcinomas with reduced E-cadherin expression showed lymph node metastasis at a rate significantly higher than that of carcinomas with normal E-cadherin expression (p<0.05). The lymph node metastasis rate (46.2%) of gastric-phenotype carcinomas with reduced E-cadherin expression was significantly higher than those of carcinomas of other phenotypes (p<0.05). CONCLUSION: Since gastric-phenotype differentiated carcinomas with reduced E-cadherin expression have the potential for becoming undifferentiated, the risk of lymph node metastasis should be considered.

Blood chimerism in monochorionic twins conceived by induced ovulation: case report.

A case of monochorionic twin boys delivered at 34 weeks of gestation following induced ovulation with clomiphene is described. One twin was typed as blood group AB and the other as B. Flow cytometry showed blood group chimerism. DNA polymorphism analysis of peripheral lymphocytes and hair root cells showed that the chimerism was confined to the blood cells and they were dizygotic.

A treatment using STI571 for jejunal gastrointestinal stromal tumor (GIST) accompanied with liver metastasis and peritoneal dissemination.

A 64-year-old man with a chief complaint of melena visited our emergency outpatient clinic. After several examinations, he was diagnosed as a gastrointestinal stromal tumor (GIST) with liver metastasis. Surgical resection of the jejunal lesion and postoperative adjuvant therapy with STI571 for one year was performed. Due to recent immunohistological studies and introduction of STI571, the diagnosis, treatment, and prognosis of GIST are about to change profoundly. Further accumulation of cases is necessary to investigate the diagnosis, treatment, and prognosis of GIST.