Electrophysiology, molecular modelling, and functional analysis of the effects of dietary quercetin and flavonoid analogues on Kir6.1 channels in rat stomach fundus smooth muscle.

Flavonoids, ubiquitously distributed in the plant world, are regularly ingested with diets rich in fruit, vegetables, wine, and tea. During digestion, they are partially absorbed in the stomach. The present work aimed to assess the in vitro effects of quercetin and ten structurally related flavonoids on the rat gastric fundus smooth muscle, focussing on ATP-dependent K+ (Kir6.1) channels, which play a central role in the regulation of resting membrane potential, membrane excitability and, consequently, of gastric motility. Whole-cell currents through Kir6.1 channels (IKir6.1) were recorded with the patch-clamp technique and the mechanical activity of gastric fundus smooth muscle strips was studied under isometric conditions. Galangin ≈ tamarixetin > quercetin > kaempferol > isorhamnetin ≈ luteolin ≈ fisetin > (±)-taxifolin inhibited pinacidil-evoked, glibenclamide-sensitive IKir6.1 in a concentration-dependent manner. Morin, rutin, and myricetin were ineffective. The steric hindrance of the molecule and the number and position of hydroxyl groups on the B ring played an important role in the activity of the molecule. Molecular docking simulations revealed a possible binding site for flavonoids in the C-terminal domain of the Kir6.1 channel subunit SUR2B, in a flexible loop formed by residues 251 to 254 of chains C and D. Galangin and tamarixetin, but not rutin relaxed both high K+- and carbachol-induced contraction of fundus strips in a concentration-dependent manner. Furthermore, both flavonoids shifted to the right the concentration-relaxation curves to either pinacidil or L-cysteine constructed in strips pre-contracted by high K+, rutin being ineffective. In conclusion, IKir6.1 inhibition exerted by dietary flavonoids might counterbalance their myorelaxant activity, affect gastric accommodation or, at least, some stages of digestion.

Mechanosensitive enteric neurons in the guinea pig gastric fundus and antrum.

BACKGROUND: Coping with the ingested food, the gastric regions of fundus, corpus, and antrum display different motility patterns. Intrinsic components of such patterns involving mechanosensitive enteric neurons (MEN) have been described in the guinea pig gastric corpus but are poorly understood in the fundus and antrum. METHODS: To elucidate mechanosensitive properties of myenteric neurons in the gastric fundus and antrum, membrane potential imaging using Di-8-ANEPPS was applied. A small-volume injection led to neuronal compression. We analyzed the number of MEN and their firing frequency in addition to the involvement of selected mechanoreceptors. To characterize the neurochemical phenotype of MEN, we performed immunohistochemistry. KEY RESULTS: In the gastric fundus, 16% of the neurons reproducibly responded to mechanical stimulation and thus were MEN. Of those, 83% were cholinergic and 19% nitrergic. In the antrum, 6% of the neurons responded to the compression stimulus, equally distributed among cholinergic and nitrergic MEN. Defunctionalizing the sensory extrinsic afferents led to a significant drop in the number of MEN in both regions. CONCLUSION: We provided evidence for MEN in the gastric fundus and antrum and further investigated mechanoreceptors. However, the proportions of the chemical phenotypes of the MEN differed significantly between both regions. Further investigations of synaptic connections of MEN are crucial to understand the hardwired neuronal circuits in the stomach.

[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.

Functional and anatomical gastric regions and their relations to motility control.

The common occurrence of gastric disorders, the accelerating emphasis on the role of the gut-brain axis, and development of realistic, predictive models of gastric function, all place emphasis on increasing understanding of the stomach and its control. However, the ways that regions of the stomach have been described anatomically, physiologically, and histologically do not align well. Mammalian single compartment stomachs can be considered as having four anatomical regions fundus, corpus, antrum, and pyloric sphincter. Functional regions are the proximal stomach, primarily concerned with adjusting gastric volume, the distal stomach, primarily involved in churning and propelling the content, and the pyloric sphincter that regulates passage of chyme into the duodenum. The proximal stomach extends from the dome of the fundus to a circumferential band where propulsive waves commence (slow waves of the pacemaker region), and the distal stomach consists of the pacemaker region and the more distal regions that are traversed by waves of excitation, that travel as far as the pyloric sphincter. Thus, the proximal stomach includes the fundus and different extents of the corpus, whereas the distal stomach consists of the remainder of the corpus and the antrum. The distributions of aglandular regions and of specialized glands, such as oxyntic glands, differ vastly between species and, across species, have little or no relation to anatomical or functional regions. It is hoped that this review helps to clarify nomenclature that defines gastric regions that will provide an improved basis for drawing conclusions for different investigations of the stomach.

Clinicopathological Features and the Prevalence of Oxyntic Gland Neoplasm: A Single-center Retrospective Study.

Objective We explored the clinicopathological characteristics and disease frequency of oxyntic gland neoplasms (OGNs). Methods We retrospectively evaluated the data of patients pathologically diagnosed with OGN at an internal medicine clinic. Patients A total of 13,240 upper gastrointestinal endoscopies were performed on 7,488 patients between December 1, 2017, and March 31, 2021. Results We identified 27 patients with 30 histopathologically confirmed OGNs, yielding a disease frequency of 0.36% (27/7,488). Furthermore, multiple simultaneous lesions were found in 3 of 27 patients (11%). One (3.3%) of the 30 lesions was present in the antrum, whereas the remaining lesions occurred in the body of the stomach. Nine (33%) of the 27 patients had no history of Helicobacter pylori infection, whereas the remaining 18 (67%) were either currently or had been previously infected. Nevertheless, 27/30 lesions (90%) still occurred in non-atrophied regions. After endoscopic treatment, a histopathological examination of the resected specimens revealed submucosal infiltration in 8 (44%) of the 18 lesions; however, none of the lesions showed submucosal desmoplasia. For all patients with submucosal involvement, only observation was performed. There were no recurrent lesions found on follow-up. Conclusion The period prevalence of OGN was 0.36%, which is much higher than previously reported. The discovery of a small submucosal appearing lesion with a faded yellow or white color and dilated microvasculature, especially in a non-atrophic area of the stomach, should raise suspicion for an OGN, which can be endoscopically managed.

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.

The role of the gastric fundus in glycemic control.

PURPOSE: Ghrelin, one of the most studied gut hormones, is mainly produced by the gastric fundus. Abundant evidence exists from preclinical and clinical studies underlining its contribution to glucose regulation. In the following narrative review, the role of the gastric fundus in glucose regulation is summarized and we investigate whether its resection enhances glycemic control. METHODS: An electronic search was conducted in the PubMed® database and in Google Scholar® using a combination of medical subject headings (MeSH). We examined types of metabolic surgery, including, in particular, gastric fundus resection, either as part of laparoscopic sleeve gastrectomy (LSG) or modified laparoscopic gastric bypass with fundus resection (LRYGBP + FR), and the contribution of ghrelin reduction to glucose regulation. RESULTS: Fourteen human studies were judged to be eligible and included in this narrative review. Reduction of ghrelin levels after fundus resection might be related to early glycemic improvement before significant weight loss is achieved. Long-term data regarding the role of ghrelin reduction in glucose homeostasis are sparse. CONCLUSION: The exact role of ghrelin in achieving glycemic control is still ambiguous. Data from human studies reveal a potential contribution of ghrelin reduction to early glycemic improvement, although further well-designed studies are needed.