Antacids and reflux esophagitis as a risk factor for gastric neoplasm of fundic-gland type: A retrospective, matched case-control study.

BACKGROUND AND AIM: Since the first report of gastric adenocarcinoma of the fundic-gland type in 2010, the clinicopathological characteristics of gastric neoplasm of the fundic-gland type (GNFG) have become clearer; however, their risk factors remain unclear. This exploratory study aimed to identify the risk factors for GNFG. METHODS: We conducted a single-center, retrospective, matched case-control study using medical information recorded at our health management center from January 2014 to July 2023. During this period, 39 240 people underwent upper gastrointestinal endoscopy. GNFG were extracted as cases and matched to controls, according to age and sex, in a 1:8 ratio, excluding those with a history of gastrointestinal surgery and those with a history or comorbidity of cancer. Univariate analysis was used to compare patient background and endoscopic findings. Multivariable analysis was performed, adjusting for factors with P values < 0.1 and antacid use. RESULTS: A total of 20 GNFG cases and 160 matched healthy controls were included. In the univariate analysis, only reflux esophagitis was significantly more common in GNFG (40.0% vs 18.1%; P = 0.036). Factors antacids and duodenitis had P values < 0.1. Logistic regression analysis was performed, adjusting for antacids, reflux esophagitis, and duodenitis. Antacids and reflux esophagitis were the independent risk factors for GNFG (odds ratio = 3.68 [95% confidence interval: 1.04-11.91] and 3.25 [95% confidence interval: 1.11-9.35]). CONCLUSIONS: Although the sample of patients with GNFG was small, antacids and reflux esophagitis were identified as a risk factor. The pathogenesis of antacids and reflux esophagitis may be involved in the development of GNFG.

[Gastric-type adenocarcinoma consisting of signet-ring cell carcinoma and adenocarcinoma of the fundic gland type:a case report].

After endoscopic treatment for esophageal cancer, a 65-year-old male underwent surveillance esophagogastroduodenoscopy. A 12-mm discolored flat lesion was noted on the greater curvature of the middle gastric body. Magnifying endoscopy with blue laser imaging demonstrated an irregular papillary surface. Biopsy revealed atypical cells with mucus and irregularly distributed nuclei. The lesion was diagnosed as a gastric-type neoplasm with low atypia. Thereafter, endoscopic submucosal dissection (ESD) was conducted and specimen was sent for biopsy. The ESD specimen suggested a signet-ring cell carcinoma with MUC5AC-positive phenotype and adenocarcinoma of the fundic gland type, with MUC6 positivity and pepsinogen I positivity in the shallow and deeper layers, respectively. Moreover, the cervical region of fundic glands demonstrated a transformation zone of the signet-ring cell carcinoma into an adenocarcinoma of the fundic gland type. Herein, we report this rare case along with a literature review.

Twenty cases of gastric adenocarcinoma of the fundic gland type.

BACKGROUND: Gastric adenocarcinoma of the fundic gland type is a new subtype of gastric adenocarcinoma. In 2019, the World Health Organization (WHO) listed gastric adenocarcinoma of the fundic gland type (GA-FG) as a new and rare gastric tumour with a low incidence due to the small number of cumulative cases worldwide. Twenty cases of GA-FG found in our centre were retrospectively analysed to improve the diagnostic ability of endoscopy and pathology in this disease. OBJECTIVE: To investigate the clinicopathological features of fundus-derived gastric tumours and to improve the understanding of and diagnostic accuracy of endoscopy for this disease. METHODS: The clinicopathological characteristics of 20 GA-FG cases between 2018 and 2022 were analysed using clinical and follow-up data and endoscopic, immunohistochemical, and pathological morphology characteristics. RESULTS: In all cases, GA-FG was found in the fundus and the body of the stomach. In total, there were 19 patients with 20 lesions, with most of the patients having a single lesion. One patient had multiple lesions, and another patient had complications from signet ring cell carcinoma (SRCC). All lesions occurred in non-atrophic areas, and 10 patients had gastric fundic gland polyps simultaneously. There were 14 cases of gastric fundus adenocarcinoma and 6 cases of acid-secreting adenoma. Fourteen lesions were treated with endoscopic submucosal dissection (ESD), without recurrence or metastasis during the follow up; 6 patients were followed up for observation, 2 of whom showed no lesions after the first biopsy by gastric endoscopy, and 4 of whom showed no significant changes. CONCLUSIONS: The incidence rate for GA-FG lesions may be underestimated due to their benign course. ESD seems to be an adequate treatment for GA-FG. MAIN POINTS: Gastric adenocarcinoma of the fundic gland type (GA-FG) is located in the fundus and body of the stomach. All lesions occur in non-atrophic areas, and almost one-half involve gastric fundus polyps simultaneously. GA-FG lesions typically follow a benign disease course. ESD seems to be an adequate treatment for GA-FG.

Wnt/ß-catenin promotes gastric fundus specification in mice and humans.

Despite the global prevalence of gastric disease, there are few adequate models in which to study the fundus epithelium of the human stomach. We differentiated human pluripotent stem cells (hPSCs) into gastric organoids containing fundic epithelium by first identifying and then recapitulating key events in embryonic fundus development. We found that disruption of Wnt/ß-catenin signalling in mouse embryos led to conversion of fundic to antral epithelium, and that ß-catenin activation in hPSC-derived foregut progenitors promoted the development of human fundic-type gastric organoids (hFGOs). We then used hFGOs to identify temporally distinct roles for multiple signalling pathways in epithelial morphogenesis and differentiation of fundic cell types, including chief cells and functional parietal cells. hFGOs are a powerful model for studying the development of the human fundus and the molecular bases of human gastric physiology and pathophysiology, and also represent a new platform for drug discovery.

Band-assisted endoscopic mucosal resection for small (≤ 1.5 cm) submucosal tumors originating from the muscularis propria in the gastric fundus: a prospective study.

BACKGROUND: To date, no prospective study has compared the safety and efficacy of band-assisted endoscopic mucosal resection (BA-EMR) with those of endoscopic dissection (ESD) for the treatment of submucosal tumors (SMTs) in the gastric fundus. We aimed to compare the safety and efficacy of BA-EMR with those of ESD for SMTs ≤ 1.5 cm in the gastric fundus. METHODS: In total, 62 patients with SMTs ≤ 1.5 cm in the gastric fundus underwent band ligation; the lesions that could be completely ligated were excised using a snare, while others were removed by ESD. RESULTS: Of 62 patients, 42 had their lesions completely ligated by the band and underwent BA-EMR, while 20 had lesions that could not be completely ligated and underwent ESD. The average tumor size was 0.94 ± 0.16 and 1.30 ± 0.16 cm in the BA-EMR and ESD groups, respectively. Compared with ESD, BA-EMR had significantly fewer complications and a significantly shorter mean operating time and hospital stay. CONCLUSION: BA-EMR is a safe and effective method for small SMTs in the gastric fundus, but is only suitable for SMTs < 1.2 cm. For small SMTs (< 1.2 cm) in the gastric fundus, BA-EMR may simplify the treatment procedure, shorten the operation time, and reduce complications.

Defining the Molecular Mechanisms of the Relaxant Action of Adiponectin on Murine Gastric Fundus Smooth Muscle: Potential Translational Perspectives on Eating Disorder Management.

Adiponectin (ADPN), a hormone produced by adipose tissue, facilitates gastric relaxation and can be a satiety signal in the network connecting peripheral organs and the central nervous system for feeding behavior control. Here, we performed preclinical research by morpho-functional analyses on murine gastric fundus smooth muscle to add insights into the molecular mechanisms underpinning ADPN action. Moreover, we conducted a clinical study to evaluate the potential use of ADPN as a biomarker for eating disorders (ED) based on the demonstrated gastric alterations and hormone level fluctuations that are often associated with ED. The clinical study recruited patients with ED and healthy controls who underwent blood draws for ADPN dosage and psychopathology evaluation tests. The findings of this basic research support the ADPN relaxant action, as indicated by the smooth muscle cell membrane pro-relaxant effects, with mild modifications of contractile apparatus and slight inhibitory effects on gap junctions. All of these actions engaged the ADPN/nitric oxide/guanylate cyclase pathway. The clinical data failed to unravel a correlation between ADPN levels and the considered ED, thus negating the potential use of ADPN as a valid biomarker for ED management for the moment. Nevertheless, this adipokine can modulate physiological eating behavior, and its effects deserve further investigation.

A "push-and-pull" trick for endoscopic removal of buckyballs impacted in the esophagus and gastric fundus.

As a common foreign body in children, magnet ingestion has been a widespread health issue. Unlike single magnet, ingestion of multiple magnets, especially those high-powered like Buckyballs could cause significant GI injury, e.g., perforation and fistula. Hereby we present a "push-and-pull" trick for management of a rare circumstance of Buckyballs ingestion.

Primary gastric leiomyosarcoma presenting as a giant polyp.

We present the case of a 35-year-old woman with previous hereditary retinoblastoma treated with radiotherapy, admitted due to severe iron deficiency anemia. Upper endoscopy and endoscopic ultrasound revealed a 5-cm polypoid lesion in the fundus arising from muscularis mucosa. Histological findings favored a sarcoma with muscular differentiation. After exclusion of metastatic disease, the patient underwent surgery and diagnosis of primary gastric leiomyosarcoma was confirmed. We report a case of double rarity of gastric leiomyosarcoma, as she presented with severe anaemia from a polypoid lesion of the gastric fundus.

[Clinical and pathological characteristics of gastric adenocarcinoma of fundic gland type].

To analyze the clinical, endoscopic and pathological feature of gastric adenocarcinoma of fundic gland type (GA-FG) (18 cases) collected from Sir Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine and Taizhou Hospital of Zhejiang Province from January 2019 to July 2022. There were 18 cases of patient of GA-FG, including male 12 cases, female 6 cases, aged from 38 to 78 years old, with average age of 60.5 years old. Gastroscopy showed that bulging or flat lesions of gastric fundus were 0.2-5.5 cm in size, and the mucosal surface was smooth, redness or rough. Histologic examination showed that tumor cells were dominated by chief cells and scattered with a few oxyntic cells, formed a complex gland that anastomoses each other, and infiltrated to the submucosa. The results of immunohistochemistry showed that tumor cells were positive for the expression of mucin-6 (MUC6) and Pepsinogen 1, and partial expression of synaptophysin (Syn). GA-FG is a rare type of gastric adenocarcinoma with good differentiation, and currently only a few cases have been reported, and often easily been misdiagnosed or missed. Therefore, to master the characteristics of clinic and pathology is helpful to improve the ability of clinical pathologists in differential diagnosis.

An evaluation of the use of double-curved endoscopes for gastric gastrointestinal stromal tumors.

BACKGROUND: Endoscopic full-thickness resection (EFTR) is a standard treatment method for gastric gastrointestinal stromal tumors (gGISTs). Evidence of the safety and efficacy of a double-curved endoscope (DCE) in EFTR of gGISTs is limited. We aimed to compare the operative outcomes of DCE versus single-curved endoscopes (SCE) in EFTR of gGISTs. MATERIAL AND METHODS: This retrospective observational study was conducted at four Chinese tertiary institutes. From January 2019 to November 2021, 104 patients who underwent EFTR by SCE (n = 57) or DCE (n = 47) were enrolled. One-to-one propensity score matching (PSM) was performed between the two groups to compare the demographics and operative outcomes. RESULTS: All gGISTs were resected successfully with no recurrence during follow-up. The median (range) tumor size was 1.2 (0.5, 3.5) cm in DCE and 2.0 (0.6, 4.8) cm in SCE (p < .001), and the procedure time was shorter in the DCE group than in the SCE group (50.0 min vs. 62.0 min, p < .05). After PSM, 41 pairs were selected, and no difference was noted in demographics. The procedure time was also shorter in the DCE group than in the SCE group (50.0 min vs. 55.0 min, p < .05). Subgroup analysis showed that the DCE group had a shorter procedure time in the gastric fundus than the SCE group (47.0 min vs. 55.0 min, p < .05). In multiple linear regression analysis, significant factors related to prolonged procedure time were the type of endoscope of SCE and larger tumor size (p < .05). CONCLUSIONS: EFTR of gGISTs using DCE is safe and effective. Compared with SCE, DCE had an advantage in terms of operative time, especially in the gastric fundus.

Calcium transients in intramuscular interstitial cells of Cajal of the murine gastric fundus and their regulation by neuroeffector transmission.

Enteric neurotransmission is critical for coordinating motility throughout the gastrointestinal (GI) tract. However, there is considerable controversy regarding the cells that are responsible for the transduction of these neural inputs. In the present study, utilization of a cell-specific calcium biosensor GCaMP6f, the spontaneous activity and neuroeffector responses of intramuscular ICC (ICC-IM) to motor neural inputs was examined. Simultaneous intracellular microelectrode recordings and high-speed video-imaging during nerve stimulation was used to reveal the temporal relationship between changes in intracellular Ca2+ and post-junctional electrical responses to neural stimulation. ICC-IM were highly active, generating intracellular Ca2+ -transients that occurred stochastically, from multiple independent sites in single ICC-IM. Ca2+ -transients were not entrained in single ICC-IM or between neighbouring ICC-IM. Activation of enteric motor neurons produced a dominant inhibitory response that abolished Ca2+ -transients in ICC-IM. This inhibitory response was often preceded by a summation of Ca2+ -transients that led to a global rise in Ca2+ . Individual ICC-IM responded to nerve stimulation by a global rise in Ca2+ followed by inhibition of Ca2+ -transients. The inhibition of Ca2+ -transients was blocked by the nitric oxide synthase antagonist l-NNA. The global rise in intracellular Ca2+ was inhibited by the muscarinic antagonist, atropine. Simultaneous intracellular microelectrode recordings with video-imaging revealed that the rise in Ca2+ was temporally associated with rapid excitatory junction potentials and the inhibition of Ca2+ -transients with inhibitory junction potentials. These data support the premise of serial innervation of ICC-IM in excitatory and inhibitory neuroeffector transmission in the proximal stomach. KEY POINTS: The cells responsible for mediating enteric neuroeffector transmission remain controversial. In the stomach intramuscular interstitial cells of Cajal (ICC-IM) were the first ICC reported to receive cholinergic and nitrergic neural inputs. Utilization of a cell specific calcium biosensor, GCaMP6f, the activity, and neuroeffector responses of ICC-IM were examined. ICC-IM were highly active, generating stochastic intracellular Ca2+ -transients. Stimulation of enteric motor nerves abolished Ca2+ -transients in ICC-IM. This inhibitory response was preceded by a global rise in intracellular Ca2+ . Individual ICC-IM responded to nerve stimulation with a rise in Ca2+ followed by inhibition of Ca2+ -transients. Inhibition of Ca2+ -transients was blocked by the nitric oxide synthase antagonist l-NNA. The global rise in Ca2+ was inhibited by the muscarinic antagonist atropine. Simultaneous intracellular recordings with video imaging revealed that the global rise in intracellular Ca2+ and inhibition of Ca2+ -transients was temporally associated with rapid excitatory junction potentials followed by more sustained inhibitory junction potentials. The data presented support the premise of serial innervation of ICC-IM in excitatory and inhibitory neuroeffector transmission in the proximal stomach.

High interobserver variability and frequent overdiagnosis of dysplasia in fundic gland polyps can be improved by detecting atypia on the surface epithelium and an abrupt transition to non-neoplastic cells.

AIMS: Fundic gland polyps (FGPs) arise sporadically and in combination with familial adenomatous polyposis (FAP). Criteria for distinguishing low-grade dysplasia (LGD) from regenerative atypia in FGPs are not well established. The aims of study were to determine: (i) interobserver variability in diagnosing LGD in FGPs; (ii) bias in diagnosing LGD in FAP patients; and (iii) stringent criteria for LGD in FGPs. METHODS AND RESULTS: Five senior pathologists who were blinded to the clinical history reviewed 72 FAP-associated FGPs and 34 sporadic FGPs. Cases were classified as negative (score = 0) or positive (score = 1) for LGD. Each case was assigned a 'combined dysplasia score' (CDS) ranging from 0 to 5 to reflect all five opinions. Fleiss' kappa showed only moderate interobserver agreement (κ = 0.46). Forty-one FGPs were classified as negative for dysplasia by consensus (CDS = 0-1), including 10 (24%) originally diagnosed as LGD. In contrast, all 37 cases classified as LGD by consensus (CDS = 4-5) were originally diagnosed as LGD, indicating that overdiagnosis of dysplasia is more common than underdiagnosis (P = 0.0012). Cytological atypia in the surface epithelium and an abrupt transition between atypical and normal-appearing epithelium were the most sensitive (97% and 100%, respectively) and specific (100% and 98%, respectively) features of dysplasia (P < 0.0001 for both comparisons). Very good agreement was achieved when a diagnosis of dysplasia was based on the presence of both features (κ = 0.85). CONCLUSIONS: There is high interobserver variability and a tendency to overdiagnose LGD in FGPs. Strict criteria requiring both surface atypia and abrupt transition for LGD in FGPs result in low interobserver variability.

Fundic gland polyps related to diverse aetiologies show subtle morphological differences: a multicentre retrospective study.

AIMS: Fundic gland polyps (FGPs) comprise 66% of all gastric polyps. Although they are usually non-syndromic, they may be associated with various syndromes, including familial adenomatous polyposis (FAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). We aimed to evaluate how histological features relate to distinct FGP subtypes. METHODS AND RESULTS: We performed a retrospective analysis of 118 FGPs from 109 patients for the architecture of fundic glands, microcyst lining, parietal cell hyperplasia and surface foveolar epithelial changes. Age, gender and history of FAP or GAPPS were collected. Based on combinations of histological features, three distinct patterns (A, B and C) of FGPs were delineated and correlated to the aetiologies. Non-syndromic FGPs were well-formed polyps composed of disordered fundic glands with intermediate-sized microcysts typically lined by a mixture of oxyntic and mucin-secreting cells (73%). Parietal cell hyperplasia (80%) and foveolar surface hyperplasia (78%) were common. FAP-associated cases demonstrated small microcysts that were predominantly lined by fundic epithelium (77%), with limited parietal cell hyperplasia (27%); foveolar hyperplasia was uncommon. GAPPS-related polyps were the largest, with prominent, mucin-secreting epithelium-lined microcysts (73%). Hyperproliferative aberrant pits were universally present, whereas parietal cell hyperplasia was uncommon. Pattern A was identified in most non-syndromic FGPs (74%) and in a minority of FAP-related FGPs (26%). The majority (82%) of FAP-related FGPs showed pattern B, but only 18% of non-syndromic FGPs did. Pattern C consisted exclusively of GAPPS-associated polyps. CONCLUSIONS: We conclude that, although FGPs share similar histomorphology, subtle differences exist between polyps of different aetiology. In the appropriate clinical setting, the recognition of these variations may help to consider syndromic aetiologies.

The role of l-cysteine/Hydrogen sulfide pathway on ß3-Adrenoceptor- induced relaxation in mouse gastric fundus.

In this study, we investigated the possible role of the l-cysteine/hydrogen sulfide pathway in ß3-adrenoceptors-mediated relaxation in isolated mouse gastric fundus tissue. l-cysteine (endogenous H2S; 10-6-10-2 M), sodium hydrogen sulfide (NaHS; exogenous H2S; 10-6-10-3 M), selective ß3-adrenoceptors agonist BRL 37344 (10-9-10-4 M) and non-selective ß-adrenoceptor agonist isoprenaline (10-9-10-4 M) produced concentration-dependent relaxation in mouse gastric fundus. The non-selective ß-adrenoceptors antagonist propranolol (10-6 M) inhibited the relaxant response to isoprenaline but not to BRL 37344. On the other hand, the selective ß3-adrenoceptors antagonist SR 59230A (10-5 M) inhibited the relaxant responses to BRL 37344. In addition, cystathionine-gamma-lyase (CSE) inhibitor D,L-propargylglycine (PAG, 10-2 M), cystathionine-beta-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10-2 M), and the combination of these inhibitors significantly reduced the relaxant responses induced by l-cysteine and BRL 37344. Pre-incubation of gastric fundal strips with propranolol (10-6 M) and SR 59230A (10-5 M) did not affect relaxations to l-cysteine and NaHS. Also, the existence of CSE, CBS, 3-mercaptopurivate sulfur transferase (3-MST) enzymes and ß3-adrenoceptors were detected in gastric fundal tissue. Furthermore, basal H2S release was detected in the measurements. H2S level increased in the presence of l-cysteine, NaHS, and BRL 37344. The increase in H2S level by l-cysteine and BRL 37344 decreased significantly with PAG and AOAA enzyme inhibitors. These results suggest that endogenous H2S is synthesized from l-cysteine at least by CBS and CSE enzymes. Also, ß3-adrenoceptors are found in the mouse stomach fundus and mediate BRL 37344-induced relaxations, and l-cysteine/hydrogen sulfide pathway plays a partial role in ß3-adrenoceptors-mediated relaxation in mouse gastric fundus tissue.

Identifying the Ideal Target Vessel Size for Bariatric Embolization: Histologic Analysis of Swine and Human Gastric Fundi.

This study aimed to identify the ideal arteriole size to target in bariatric embolization, with the goal of maximizing weight loss efficacy while maintaining patient safety. Although all published clinical trials of bariatric embolization have used embolic microspheres that were at least 300 µm in diameter, optimal weight loss outcomes have been achieved safely in swine using 50-µm embolics. Human fundal remnants from bariatric surgery were compared with swine fundal sections after bariatric embolization with 50-µm embolic microspheres to assess the ideal fundal vessel size for bariatric embolization. In swine, the 50-µm embolic microspheres deposited in the luminal half of the submucosa with a mean arteriole size of 49 µm ± 30. The mean arteriole diameter in the corresponding submucosal layer of the human gastric fundi was 40 µm ± 30. These measurements may inform future clinical trials and direct the development of embolic agents for bariatric embolization.

SP70 is a potential biomarker to identify gastric fundic gland neoplasms.

BACKGROUND: Gastric neoplasms with fundic gland differentiation include oxyntic gland adenomas (OGAs) and gastric adenocarcinomas of fundic gland type (GA-FGs). Due to their well-differentiated and similar morphology with normal fundic glands, it is usually challenging to identify these lesions in pathological diagnosis, especially in biopsy specimens. This study aims to explore and verify the potential role of a newly developed monoclonal antibody (McAb) NJ001 (SP70) in differentiating fundic neoplasms from non-neoplastic fundic gland lesions. METHODS: Twenty-three cases of histological confirmed gastric fundic gland neoplasms were obtained, including 12 cases of OGAs and 11 of GA-FGs. Fifty cases of fundic gland polyps (FGPs) were taken as the control group. Six cases of well-differentiated gastric neuroendocrine tumors (NETs) (easily misdiagnosed) were also obtained. Key clinicopathological information was collected. SP70 immunostaining was performed (with para-tumor normal fundic glands as internal control). The positive intensity and staining pattern of SP70 were analyzed and compared. RESULTS: In normal gastric mucosa, SP70 was strongly and diffusely stained on the cytoplasm in fundic glands, but not in the foveolar epithelium. Therefore, a zonal distribution of SP70 was observed in normal mucosa. FGPs (50/50, 100%) shared a similar expression pattern with normal fundic glands. In fundic gland neoplasms, a significant down-expression of SP70 was observed in both OGAs and GA-FGs. The positive rate of SP70 in fundic gland neoplasms (6/23, 26.1%) was significantly lower than that in FGPs (100%) (P<0.0001). There was no difference in SP70 expression between OGAs (3/12, 25.0%) and GA-FGs (3/11, 27.2%) group (P>0.05). In these 6 NET cases, SP70 was weak to moderate intensity in the majority of tumor cells (with a different expression pattern). CONCLUSION: Down-expression of SP70 is a specific feature to fundic gland neoplasms including OGAs and GA-FGs. Therefore, SP70 can serve as a potential biomarker in the identification and differential diagnosis of fundic gland neoplasms.

Neuronal Nitric Oxide Synthase as a Shared Target for the Effects of Adiponectin and Resistin on the Mechanical Responses of the Mouse Gastric Fundus.

It has been reported that adiponectin (ADPN) and resistin are co-secreted by white mouse adipocytes and exert similar inhibitory effects in the mouse gastric fundus, in which resistin was observed to increase neuronal nitric oxide synthase (nNOS) expression. On these grounds, the present work aimed to investigate whether the effects of the two adipokines on the neurally-induced relaxant responses potentiate each other and whether there is a possible correlation with changes in nNOS expression in preparations from the mouse gastric fundus. In carbachol (CCh)-precontracted strips, electrical field stimulation elicited nitrergic relaxant responses, whose amplitude was increased by ADPN or resistin, but no additional enhancements were observed in their concomitant presence. Western blot and immunofluorescence analyses revealed that ADPN, like resistin, was able to up-regulate nNOS expression and to increase the percentage of nNOS-positive neurons in the myenteric plexus: co-treatment with the two adipokines did not induce additional changes. The results indicate that the two adipokines modulate nitrergic neurotransmission, and both do so by up-regulating nNOS expression. Therefore, nNOS appears to be a shared target for the two adipokines' effects, which, rather than mutually reinforcing each other, may represent a dual physiological control mechanism to guarantee gastric fundus relaxation.

Dissecting transcriptional heterogeneity in primary gastric adenocarcinoma by single cell RNA sequencing.

OBJECTIVE: Tumour heterogeneity represents a major obstacle to accurate diagnosis and treatment in gastric adenocarcinoma (GA). Here, we report a systematic transcriptional atlas to delineate molecular and cellular heterogeneity in GA using single-cell RNA sequencing (scRNA-seq). DESIGN: We performed unbiased transcriptome-wide scRNA-seq analysis on 27 677 cells from 9 tumour and 3 non-tumour samples. Analysis results were validated using large-scale histological assays and bulk transcriptomic datasets. RESULTS: Our integrative analysis of tumour cells identified five cell subgroups with distinct expression profiles. A panel of differentiation-related genes reveals a high diversity of differentiation degrees within and between tumours. Low differentiation degrees can predict poor prognosis in GA. Among them, three subgroups exhibited different differentiation grade which corresponded well to histopathological features of Lauren's subtypes. Interestingly, the other two subgroups displayed unique transcriptome features. One subgroup expressing chief-cell markers (eg, LIPF and PGC) and RNF43 with Wnt/ß-catenin signalling pathway activated is consistent with the previously described entity fundic gland-type GA (chief cell-predominant, GA-FG-CCP). We further confirmed the presence of GA-FG-CCP in two public bulk datasets using transcriptomic profiles and histological images. The other subgroup specifically expressed immune-related signature genes (eg, LY6K and major histocompatibility complex class II) with the infection of Epstein-Barr virus. In addition, we also analysed non-malignant epithelium and provided molecular evidences for potential transition from gastric chief cells into MUC6+TFF2+ spasmolytic polypeptide expressing metaplasia. CONCLUSION: Altogether, our study offers valuable resource for deciphering gastric tumour heterogeneity, which will provide assistance for precision diagnosis and prognosis.

Characterization of the A-type potassium current in murine gastric fundus smooth muscles.

Transient outward, or "A-type," currents are rapidly inactivating voltage-gated potassium currents that operate at negative membrane potentials. A-type currents have not been reported in the gastric fundus, a tonic smooth muscle. We used whole cell voltage clamp to identify and characterize A-type currents in smooth muscle cells (SMCs) isolated from murine fundus. A-type currents were robust in these cells with peak amplitudes averaging 1.5 nA at 0 mV. Inactivation was rapid with a time constant of 71 ms at 0 mV; recovery from inactivation at -80 mV was similarly rapid with a time constant of 75 ms. A-type currents in fundus were blocked by 4-aminopyridine (4-AP), flecainide, and phrixotoxin-1 (PaTX1). Remaining currents after 4-AP and PaTX1 displayed half-activation potentials that were shifted to more positive potentials and showed incomplete inactivation. Currents after tetraethylammonium (TEA) displayed half inactivation at -48.1 ± 1.0 mV. Conventional microelectrode and contractile experiments on intact fundus muscles showed that 4-AP depolarized membrane potential and increased tone under conditions in which enteric neurotransmission was blocked. These data suggest that A-type K+ channels in fundus SMCs are likely active at physiological membrane potentials, and sustained activation of A-type channels contributes to the negative membrane potentials of this tonic smooth muscle. Quantitative analysis of Kv4 expression showed that Kcnd3 was dominantly expressed in fundus SMCs. These data were confirmed by immunohistochemistry, which revealed Kv4.3-like immunoreactivity within the tunica muscularis. These observations indicate that Kv4 channels likely form the A-type current in murine fundus SMCs.

Endoscopic sleeve gastroplasty: suturing the gastric fundus does not confer benefit.

BACKGROUND : There is heterogeneity regarding the technical aspects of endoscopic sleeve gastroplasty (ESG), such as applying fundal sutures. Our aim was to determine whether ESG with fundal suturing (ESG-FS) affects weight loss and the serious adverse event (SAE) rate when compared with ESG with no fundal suturing (ESG-NFS). METHODS: We conducted a two-center retrospective analysis of 247 patients who underwent ESG with or without fundal suturing. The primary outcome was percentage excess weight loss (%EWL) at 3, 6, and 12 months post-ESG. The secondary outcomes included the SAE rate and procedure duration. RESULTS: At 3, 6, and 12-months, ESG-NFS had a significantly greater mean %EWL compared with ESG-FS (38.4 % [standard deviation (SD) 15.3 %] vs. 31.2 % [SD 13.9 %], P = 0.001; 54.7 % [SD 19.2 %] vs. 37.7 % [SD 17.3 %], P < 0.001; 65.3 % [SD 21.1 %] vs. 40.6 % [SD 23.5 %], P < 0.001, respectively). There was no statistically significant difference in the SAE rates for ESG-NFS (n = 2; 2.0 %) and ESG-FS (n = 4; 2.6 %; P > 0.99). The mean procedure time was significantly shorter in the ESG-NFS group at 59.1 minutes (SD 32.7) vs. 93.0 minutes (35.5; P < 0.001), and a lower mean number of sutures were used, with 5.7 (SD 1.1) vs. 8.4 (SD 1.6; P < 0.001). CONCLUSION : ESG-NFS demonstrated greater efficacy and shorter procedure duration. Therefore, fundal suturing should not be performed.