Endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without Helicobacter pylori infection: a retrospective observational study

Background The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection. Methods We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group). Results The average age was older in the Hp group than in the uninfected group (68.1 +/- 8.1 vs. 63.4 +/- 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%). Conclusions The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection

Endoscopic resection is a suitable initial treatment strategy for oxyntic gland adenoma or gastric adenocarcinoma of the fundic gland type

The aim of this study was to reveal the histological features of oxyntic gland adenomas and gastric adenocarcinoma of the fundic-gland type (GA-FG). We retrospectively examined the histological features of 126 lesions of oxyntic gland adenoma and/or GA-FG in 116 patients. The prevalence of oxyntic gland adenomas and GA-FG was approximately equal. The majority of the lesions were resected by endoscopic mucosal resection using a diathermic snare (EMR, n=42) or endoscopic submucosal dissection (ESD, n=72). Histologically, there were no lesions with invasion at the level of the muscularis propria or deeper, and lymphovascular invasion was present in 1.6%. Of the ESD and EMR specimens, there were no lesions that were positive for vertical margins. Among the eight GA-FG patients with deep (>= 500 mu m) submucosal invasion, six were treated with endoscopic resection alone, and no recurrence was documented. No patients died of the disease during the median follow-up period of 14.5 months. In conclusion, all lesions were confined to the mucosa or submucosa and were negative for vertical margins. Lymphovascular invasion was present in only 1.6% of the patients. Thus, we believe that endoscopic resection is a suitable initial treatment method for oxyntic gland adenoma and GA-FG

Lesion size, elevated morphology, and non or closed-type atrophy are predictive factors for gastric adenocarcinoma of the fundic gland type rather than oxyntic gland adenoma

Background: An oxyntic gland neoplasm confined to the mucosal layer (T1a) is classified as an oxyntic gland adenoma, whereas that with submucosal invasion (T1b) is defined as gastric adenocarcinoma of the fundic gland type (GA-FG). Methods: To reveal the differences in clinical features between them, we retrospectively investigated 136 patients with 150 oxyntic gland adenoma and GA-FG lesions. Results: The univariate analysis revealed that the mean size (GA-FG vs. oxyntic gland adenoma, 7.7±5.4 vs. 5.5±3.1 mm), the prevalence of elevated morphology (79.1% vs. 51.8%), black pigmentation within the lesion (23.9% vs. 9.6%), and non or closed-type atrophy (81.2% vs. 65.1%) were different between the two groups. A multivariate logistic regression analysis revealed that ≥5 mm lesion size (odds ratio, 2.96; 95% confidence interval: 1.21–7.23), elevated morphology (odds ratio, 2.40; 95% confidence interval: 1.06–5.45), and no or closed-type atrophy (odds ratio, 2.49; 95% confidence interval: 1.07–5.80) were factors in distinguishing GA-FG from oxyntic gland adenoma. When oxyntic gland neoplasms with no or one feature were judged as oxyntic gland adenomas and those with two or three features were judged as GA-FG, the sensitivity and specificity were 85.1% and 43.4% for GA-FG, respectively. Conclusions: We identified three possible distinctive features of GA-FG compared to oxyntic gland adenoma: lesion size ≥5 mm, elevated morphology, and no or closed-type atrophy

Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages.

金沢大学医薬保健研究域医学系Idiopathic pulmonary fibrosis is a devastating disease with poor prognosis. The pathogenic role of the lysophospholipid mediator sphingosine-1-phosphate and its receptor S1PR2 in lung fibrosis is unknown. We show here that genetic deletion of S1pr2 strikingly attenuated lung fibrosis induced by repeated injections of bleomycin in mice. We observed by using S1pr2 LacZ/+ mice that S1PR2 was expressed in alveolar macrophages, vascular endothelial cells and alveolar epithelial cells in the lung and that S1PR2-expressing cells accumulated in the fibrotic legions. Bone marrow chimera experiments suggested that S1PR2 in bone marrow–derived cells contributes to the development of lung fibrosis. Depletion of macrophages greatly attenuated lung fibrosis. Bleomycin administration stimulated the mRNA expression of the profibrotic cytokines IL-13 and IL-4 and the M2 markers including arginase 1, Fizz1/Retnla, Ccl17 and Ccl24 in cells collected from broncho-alveolar lavage fluids (BALF), and S1pr2 deletion markedly diminished the stimulated expression of these genes. BALF cells from bleomycin–administered wild-type mice showed a marked increase in phosphorylation of STAT6, a transcription factor which is activated downstream of IL-13, compared with saline–administered wild-type mice. Interestingly, in bleomycin–adminis-tered S1pr2 -/- mice, STAT6 phosphorylation in BALF cells was substantially diminished compared with wild-type mice. Finally, pharmacological S1PR2 blockade in S1pr2 +/+ mice alleviated bleomycin–induced lung fibrosis. Thus, S1PR2 facilitates lung fibrosis through the mechanisms involving augmentation of IL-13 expression and its signaling in BALF cells, and represents a novel target for treating lung fibrosis. © 2018 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The Comet Interceptor Mission

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum ΔV capability of 600 ms−1. Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule

Disruption of model-based decision making by silencing of serotonin neurons in the dorsal raphe nucleus

Adaptingto changing environmentalconditions requires a prospective inferenceof future actionsandtheir consequences, a strategy alsoknownasmodel-baseddecisionmaking.(1-3) In stable environments, extensive experience of actions and their consequences leads to a shift fromamodel-based to amodel-free strategy, whereby behavioral selection is primarily governed by retrospective experiences of positive and negative outcomes. Human and animal studies, where subjects are required to speculate about implicit information and adjust behavioral responses overmultiple sessions, point to a role for the central serotonergic systeminmodel-based decision making.(4-8) However, to directly test a causal relationship between serotonergic activity and model-based decision making, phase-specific manipulation of serotonergic activity is needed in a one-shot test, where learning by trial and error is neutralized. Moreover, the serotonergic origin responsible for this effect is yet to be determined. Herein, we demonstrate that optogenetic silencing of serotonin neurons in the dorsal raphe nucleus, but not in the median raphe nucleus, disrupts model-based decision making in lithium-induced outcome devaluation tasks.(9-11) Our data indicate that the serotonergic behavioral effects are not due to increased locomotor activity, anxiolytic effects, or working memory deficits. Our findings provide insights into the neural mechanisms underlying neural weighting between model-free and model-based strategies