The addition of pembrolizumab to neoadjuvant chemoradiotherapy did not increase the risk of developing postoperative anastomotic leakage for ESCC: an analysis from a prospective cohort.

BACKGROUND: To compare the difference of postoperative anastomotic leakage (AL) rate between neoadjuvant chemoradiotherapy (NCRT) with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced esophageal squamous cell cancer (ESCC). MATERIALS AND METHODS: The GF was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established. RESULTS: A total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p < 0.05). Multivariate logistic regression analysis indicated that tumor length (p = 0.012), volume of GF (p = 0.003) and mean dose of GF (p = 0.007) were independently predictors for postoperative AL. Using receiver operating characteristics analysis, the mean dose limit on the GF was defined as 14 Gy. CONCLUSION: Based on our prospective database, no significant difference of developing AL were observed between NCRT with pembrolizumab and NCRT group. We established an individualized nomograms based on mean GF dose combined with clinical indicators to predict AL in the early postoperative period.

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.

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.

Berberine ameliorates the neurological dysfunction of the gastric fundus by promoting calcium channels dependent release of ACh in STZ-induced diabetic rats.

Background: It has been reported diabetic gastroparesis is related to diabetic autonomic neuropathy of the gastrointestinal tract, and berberine (BBR) could ameliorate diabetic central and peripheral neuropathy. However, the influence of BBR on the function and motility of the gastric fundus nerve is unclear. Methods: A diabetic rat model was constructed, and HE staining was used to observe the morphological changes in the gastric fundus. The changes in cholinergic and nitrogen-related neurochemical indexes and the effects of BBR on them were measured using Elisa. The effects of BBR on the neural function and motility of gastric fundus were investigated by electric field stimulation (EFS) induced neurogenic response in vitro. Results: In the early stage of STZ-induced diabetic rats, the contractile response of gastric fundus induced by EFS was disorder, disturbance of contraction amplitude, and the cell bodies of neurons in the myenteric plexus of gastric fundus presented vacuolar lesions. Administration with BBR could improve the above symptoms. BBR further enhanced the contraction response in the presence of a NOS inhibitor or the case of inhibitory neurotransmitters removal. Interestingly, the activity of ACh could affect NO release directly and the enhancement of BBR on contractile response was canceled by calcium channel blockers completely. Conclusions: In the early stage of STZ-induced diabetic rats, the neurogenic contractile response disorder of the gastric fundus is mainly related to cholinergic and nitrergic nerve dysfunction. BBR promotes the release of ACh mainly by affecting the calcium channel to improve the neurological dysfunction of the gastric fundus.

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.

Cholangiocarcinoma presenting as dysphagia and misdiagnosed as gastritis: a case report.

BACKGROUND: Heterotopic tumor is a rare disease. Thus far, no cases of heterotopic cholangiocarcinoma have been reported in the world. Cholangiocarcinoma mainly metastasizes by direct invasion, and it can lead to liver metastasis in its advanced stage. There were few clinical cases of gastric metastasis in advanced tumors, mainly seen in breast cancer, lung cancer, liver cancer, malignant melanoma, choriocarcinoma, and hematological tumors. Metastases of cholangiocarcinoma to the stomach also are exceptionally rare. CASE PRESENTATION: A 58-year-old man was admitted to the hospital because of difficulty swallowing for one year. Upon gastroscopy, we found the tumor at the region of the cardia and gastric fundus. Macroscopical appearance of the tumor suggested its malignant nature. Computed tomography (CT) findings showed that the wall of the cardia, fundus, and stomach body were thickened, suggesting a tumor. Because the patient had obvious difficulty swallowing, we invited cardiothoracic surgeons for consultation. They considered that the patient had definite mechanical obstruction in the lower esophagus; hence, they performed an operation. Immunohistochemical staining revealed low-to-medium differentiated adenocarcinoma (containing mucinous adenocarcinoma components) of biliary origin. CONCLUSIONS: We highlight the importance of the endoscopic biopsy of gastric tumor. However, when its results are inconsistent with the clinician's judgment, further examination is required. Endoscopic ultrasonography and enhanced CT may be a good choice. If necessary, on the premise of patient acceptance, the diagnosis could be confirmed after surgical excision. Here we report a case of a patient with heterotopic cholangiocarcinoma in the gastric fundus. The most common tissue ectopias in the digestive tract include esophagogastric gastric mucosal ectopia, duodenal gastric mucosal ectopia, and gastric mucosal small intestinal ectopia. Thus far, there have been no reports of ectopic cholangiocarcinoma and associated cancer in the stomach. In addition, metastases of cholangiocarcinoma to the stomach are also exceptionally rare, and most of them are due to a direct invasion. The discovery of the primary lesion is an important clue for the reliable diagnosis in such cases.

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.

Adiponectin Exerts Peripheral Inhibitory Effects on the Mouse Gastric Smooth Muscle through the AMPK Pathway.

Some adipokines, such as adiponectin (ADPN), other than being implicated in the central regulation of feeding behavior, may influence gastric motor responses, which are a source of peripheral signals that also influence food intake. The present study aims to elucidate the signaling pathways through which ADPN exerts its actions in the mouse gastric fundus. To this purpose, we used a multidisciplinary approach. The mechanical results showed that ADPN caused a decay of the strip basal tension, which was abolished by the nitric oxide (NO) synthesis inhibitor, L-NG-nitro arginine (L-NNA). The electrophysiological experiments confirmed that all ADPN effects were abolished by L-NNA, except for the reduction of Ca2+ current, which was instead prevented by the inhibitor of AMP-activated protein kinase (AMPK), dorsomorphin. The activation of the AMPK signaling by ADPN was confirmed by immunofluorescence analysis, which also revealed the ADPN R1 receptor (AdipoR1) expression in glial cells of the myenteric plexus. In conclusion, our results indicate that ADPN exerts an inhibitory action on the gastric smooth muscle by acting on AdipoR1 and involving the AMPK signaling pathway at the peripheral level. These findings provide novel bases for considering AMPK as a possible pharmacologic target for the potential treatment of obesity and eating disorders.

Relaxant effect of atorvastatin on isolated rat gastric fundus strips: implications for Ca2+-signalling mechanisms.

Statins are determined to have various pleiotropic effects apart from their lipid-lowering properties. Herein, we investigated the direct effects of atorvastatin on gastric smooth muscle tone. Atorvastatin effectively relaxed isolated rat gastric fundus strips precontracted with acetylcholine, potassium chloride, and serotonin. Incubation of the strips with nitric oxide synthase inhibitor, l-NOARG (10-4 M, 20 min), l-type voltage-operated Ca2+ channel (VOCC) blocker, nifedipine (10-6 M, 30 min), KATP channel blocker, glibenclamide (10-5 M, 30 min), or precursor of cholesterol, mevalonate (10-2 M, 45 min) did not change the relaxations to atorvastatin. However, pretreatment of fundus strips with atorvastatin (3×10-5-3×10-4 M, 30 min) inhibited the contractions to calcium chloride (10-4-10-1 M), acetylcholine (10-4 M), and caffeine (20 mM) in the calcium-free medium. Moreover, atorvastatin reduced the contractions induced by sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, cyclopiazonic acid (10-7-3×10-5 M). The current study demonstrated that atorvastatin produces an acute relaxant effect on gastric fundus strips, which appears to be mediated by several Ca2+-signalling mechanisms such as the blockade of l-type VOCC-independent Ca2+ entry, decrease in smooth muscle Ca2+ sensitivity, inhibition of IP3- and ryanodine-sensitive intracellular stores to mediate Ca2+ release, as well as the activation of SERCA. This acute relaxing effect seems unlikely to be related with nitric oxide, KATP channels, and the mevalonate pathway.

A role for focal adhesion kinase in facilitating the contractile responses of murine gastric fundus smooth muscles.

KEY POINTS: Activation of focal adhesion kinase (FAK) by integrin signalling facilitates smooth muscle contraction by transmitting the force generated by myofilament activation to the extracellular matrix and throughout the smooth muscle tissue. Here we report that electrical field stimulation (EFS) of cholinergic motor neurons activates FAK in gastric fundus smooth muscles, and that FAK activation by EFS is atropine-sensitive but nicardipine-insensitive. PDBu and calyculin A contracted gastric fundus muscles Ca2+ -independently and also activated FAK. Inhibition of FAK activation inhibits the contractile responses evoked by EFS, and inhibits CPI-17 phosphorylation at T38. This study indicates that mechanical force or tension is sufficient to activate FAK, and that FAK appears to be involved in the activation of the protein kinase C-CPI-17 Ca2+ sensitization pathway in gastric fundus smooth muscles. These results reveal a novel role for FAK in gastric fundus smooth muscle contraction by facilitating CPI-17 phosphorylation. ABSTRACT: Smooth muscle contraction involves regulating myosin light chain phosphorylation and dephosphorylation by myosin light chain kinase and myosin light chain phosphatase. C-kinase potentiated protein phosphatase-1 inhibitor of 17 kDa (CPI-17) and myosin phosphatase targeting subunit of myosin light-chain phosphatase (MYPT1) are crucial for regulating gastrointestinal smooth muscle contraction by inhibiting myosin light chain phosphatase. Integrin signalling involves the dynamic recruitment of several proteins, including focal adhesion kinase (FAK), to focal adhesions. FAK tyrosine kinase activation is involved in cell adhesion to the extracellular matrix via integrin signalling. FAK participates in linking the force generated by myofilament activation to the extracellular matrix and throughout the smooth muscle tissue. Here, we show that cholinergic stimulation activates FAK in gastric fundus smooth muscles. Electrical field stimulation in the presence of Nω -nitro-l-arginine methyl ester and MRS2500 contracted gastric fundus smooth muscle strips and increased FAK Y397 phosphorylation (pY397). Atropine blocked the contractions and prevented the increase in pY397. The FAK inhibitor PF-431396 inhibited the contractions and the increase in pY397. PF-431396 also inhibited the electrical field stimulation-induced increase in CPI-17 T38 phosphorylation, and reduced MYPT1 T696 and T853, and myosin light chain S19 phosphorylation. Ca2+ influx was unaffected by PF-431396. Nicardipine inhibited the contractions but had no effect on the increase in pY397. Phorbol 12,13-dibutyrate or calyculin A contracted gastric fundus smooth muscle strips Ca2+ independently and increased pY397. Our findings suggest that FAK is activated by mechanical forces during contraction and reveal a novel role of FAK in the regulation of CPI-17 phosphorylation.

Gastric Mammalian Target of Rapamycin Signaling Contributes to Inhibition of Ghrelin Expression Induced by Roux-En-Y Gastric Bypass.

BACKGROUND/AIMS: Roux-en-Y Gastric Bypass, RYGB, is the most effective strategy to control body weight in morbid obesity. RYGB leads to rapid improvement of glycemic status and weight loss, which are largely attributed to the alteration of gastrointestinal hormones including ghrelin. The current study examined potential mechanisms of altered ghrelin synthesis after RYGB. METHODS: Gastric mammalian target of rapamycin (mTOR) signaling, ghrelin synthesis and secretion were determined in lean or obese male mice with or without RYGB operation, as well as in obese patients pre- and post-RYGB surgery. Ghrelin expression and mTOR signaling were investigated by western blotting and immunohistochemistry. Ghrelin mRNA levels were detected by real-time PCR. Plasma ghrelin was measured by enzyme immunoassay. RESULTS: mTOR activity in the gastric fundus was significantly lower than in the forestomachs. Both of them were decreased after 24h fasting. A significant negative correlation was found between gastric levels of phospho-S6 (phospho-S6 ribosomal protein) and proghrelin during changes of energy status. mTOR activity was activated, whereas ghrelin expression was inhibited by Roux-en-Y Gastric Bypass in both rodents and human beings. Increment of ghrelin synthesis and decline of mTOR signaling induced by rapamycin were significantly reversed by RYGB in both lean and obese mice. Administration of Ad-S6K1 (adenovirus-mediated p70 ribosomal protein subunit 6 kinase 1) from tail vein suppressed the expression of ghrelin in RYGB-operated mice relative to control animals. CONCLUSION: mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of ghrelin after Roux-en-Y Gastric Bypass.

Acid-gastric antisecretory effect of the ethanolic extract from Arctium lappa L. root: role of H+, K+-ATPase, Ca2+ influx and the cholinergic pathway.

BACKGROUND: Arctium lappa L., popularly known as burdock, is a medicinal plant used worldwide. The antiulcer and gastric-acid antisecretory effects of ethanolic extract from roots of Arctium lappa (EET) were already demonstrated. However, the mechanism by which the extract reduces the gastric acid secretion remains unclear. Therefore, this study was designed to evaluate the antisecretory mode of action of EET. MATERIALS AND METHODS: The effects of EET on H+, K+-ATPase activity were verified in vitro, whereas the effects of the extract on cholinergic-, histaminergic- or gastrinergic-acid gastric stimulation were assessed in vivo on stimulated pylorus ligated rats. Moreover, ex vivo contractility studies on gastric muscle strips from rats were also employed. RESULTS: The incubation with EET (1000 µg/ml) partially inhibited H+, K+-ATPase activity, and the intraduodenal administration of EET (10 mg/kg) decreased the volume and acidity of gastric secretion stimulated by bethanechol, histamine, and pentagastrin. EET (100-1000 µg/ml) did not alter the gastric relaxation induced by histamine but decreased acetylcholine-induced contraction in gastric fundus strips. Interestingly, EET also reduced the increase in the gastric muscle tone induced by 40 mM KCl depolarizing solution, as well as the maximum contractile responses evoked by CaCl2 in Ca2+-free depolarizing solution, without impairing the effect of acetylcholine on fundus strips maintained in Ca2+ -free nutritive solution. CONCLUSION: Our results reinforce the gastric antisecretory properties of preparations obtained from Arctium lappa, and indicate that the mechanisms involved in EET antisecretory effects include a moderate reduction of the H+, K+-ATPase activity associated with inhibitory effects on calcium influx and of cholinergic pathways in the stomach muscle.

H2 S-induced gastric fundus smooth muscle tension potentiation is mediated by the phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase pathway.

NEW FINDINGS: What is the central question of this study? The present study investigated the relationship between H2 S and NO in regulation of gastric fundus tension. What is the main finding and its importance? Endogenous or exogenous H2 S and NO have opposite effects on fundus tension, and H2 S-induced gastric fundus tension enhancements are mediated by inhibition of NO generation through the phosphoinositide 3-kinase/Akt pathway. These results are very important in exploring the mechanism of physiological accommodation and accommodation disorder. Hydrogen sulphide (H2 S) is considered a new gasotransmitter, along with NO and CO. It was recently confirmed that H2 S and NO play important roles in the regulation of gastrointestinal smooth muscle tension. The present study was designed to elucidate the interactions between H2 S and NO with respect to the regulation of gastric fundus smooth muscle tension using Western blotting, physiological and electrochemical techniques. Real-time H2 S and NO generation was detected in gastric smooth muscle tissue. NaHS, an H2 S donor, enhanced fundus smooth muscle tension, whereas SNP, an NO donor, decreased fundus smooth muscle tension in a dose-dependent manner. NaHS-induced increases in fundus smooth muscle tension were suppressed by l-NAME, an NO synthase inhibitor. Aminooxyacetic acid (AOAA), a cystathionine ß-synthase inhibitor, exerted inhibitory effects on fundus smooth muscle tension; these effects were also suppressed by l-NAME. Real-time NO generation was significantly potentiated by AOAA. Endothelial nitric oxide synthase (eNOS) phosphorylation at serine 1177 and Akt phosphorylation at serine 308 and threonine 473 were significantly inhibited by NaHS. LY294002, a phosphoinositide 3-kinase inhibitor, blocked these NaHS-mediated effects. However, eNOS phosphorylation at serine 1177 and Akt phosphorylation at serine 308 and threonine 473 were significantly potentiated by AOAA. Cystathionine ß-synthase siRNA interference significantly increased eNOS phosphorylation at serine 1177 and Akt phosphorylation at serine 308 and threonine 473. Cystathionine ß-synthase siRNA interference also increased total eNOS protein expression levels but did not significantly change total Akt kinase protein expression levels. These results suggest that H2 S-induced enhancement of gastric fundus tension is mediated by inhibition of NO generation through the phosphoinositide 3-kinase/Akt pathway.

Overexpression of Na+/Ca2+ exchanger 1 display enhanced relaxation in the gastric fundus.

In gastric smooth muscles, the released Ca2+ activates the contractile proteins and Ca2+ taken up from the cytosol cause relaxation. The Na+/Ca2+ exchanger (NCX) is an antiporter membrane protein that controls Ca2+ influx and efflux across the membrane. However, the possible relation of NCX in gastric fundus motility is largely unknown. Here, we investigated electric field stimulation (EFS)-induced relaxations in the circular muscles of the gastric fundus in smooth muscle-specific NCX1 transgenic mice (Tg). EFS caused a bi-phasic response, transient and sustained relaxation. The sustained relaxation prolonged for an extended period after the end of the stimulus. EFS-induced transient relaxation and sustained relaxation were greater in Tg than in wild-type mice (WT). Disruption of nitric oxide component by N-nitro-l-arginine, EFS-induced transient and sustained relaxations caused still marked in Tg compared to WT. Inhibition of PACAP by antagonist, EFS-induced sustained relaxation in Tg was not seen, similar to WT. Nevertheless, transient relaxation remained more pronounced in Tg than in WT. Next, we examined responses to NO and PACAP in smooth muscles. The magnitudes of NOR-1, which generates NO, and PACAP-induced relaxations were greater in Tg than in WT. In this study, we demonstrate that NCX1 regulates gastric fundus motility.

Relationship between gastric pouch and weight loss after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is considered safe and effective even as conversion procedure after primary bariatric operations. The correlation between gastric pouch volumes and patients weight loss remains unclear. METHODS: To assess a correlation between the gastric remnant size and the weight loss, we reviewed 49 consecutive barium swallow UGS performed at our institute from August 2012 through May 2014 in LSG patients with symptoms and/or unsatisfactory weight loss. The anteroposterior (AP), laterolateral (LL) and vertical (CC) diameters of the gastric pouch were measured to calculate the volume by the formula of the ellipsoid (AP × LL × CC × 0.5). Patients were divided in two groups: group 1 without gastric pouch (n = 36) and group 2 with gastric pouch (n = 13). Correlation between pouch volume and weight loss data was calculated with t Student's and Fisher tests to compare the percent excess body mass index (BMI) and percent excess body mass loss (EBL) between two groups, and P < 0.05 was considered statistically significant. RESULTS: The mean percent EBL was 26.54 ± 11.02 and 27.12 ± 12.35 kg/m(2) in groups with and without pouch, respectively. The mean volume of the pouch after LSG was 17.13 ± 21.56 mm(3). Pouch volume, when present, was not significantly correlated to weight loss (P = 0.88 95% CI, CL 19.88-33.20 group 2; CL 22.94-31.30 group 1). CONCLUSIONS: No statistical correlation was found between the volume of the gastric pouch and weight loss (percent EBL) after LSG in symptomatic or with unsatisfactory weight loss patients.

Gastric and lower esophageal sphincter pressures during nausea: a study using visual motion-induced nausea and high-resolution manometry.

Nausea is the subjective unpleasant sensation that immediately precedes vomiting. Studies using barostats suggest that gastric fundus and lower esophageal sphincter (LES) relaxation precede vomiting. Unlike barostat, high-resolution manometry allows less invasive, detailed measurements of fundus pressure (FP) and axial movement of the gastroesophageal junction (GEJ). Nausea was induced in 12 healthy volunteers by a motion video and rated on a visual analog scale. FP was measured as the mean value of the five pressure channels that were clearly positioned below the LES. After intubation, a baseline (BL) recording of 15 min was obtained. This was followed by presentation of the motion video (at least 10 min, maximum 20 min) followed by 30 min recovery recording. Throughout the experiment we recorded autonomic nervous system (ANS) parameters [blood pressure, heart rate (HR), and cardiac vagal tone (CVT), which reflects efferent vagal activity]. Ten out of 12 subjects showed a drop in FP during peak nausea compared with BL (-4.0 ± 0.8 mmHg; P = 0.005), and 8/10 subjects showed a drop in LES pressure (-8.8 ± 2.5 mmHg; P = 0.04). Peak nausea preceded peak fundus and LES pressure drop. Nausea was associated with configuration changes at the GEJ such as LES shortening and esophageal lengthening. During nausea we observed a significantly increased HR and decreased CVT. In conclusion, nausea is associated with a drop in fundus and LES pressure, configuration changes at the GEJ as well as changes in the ANS activity such as an increased sympathetic tone (increased HR) and decreased parasympathetic tone (decreased CVT).

Oxyntic Gland Neoplasms - From Adenoma to Advanced Gastric Cancer: A Review of 29 Cases.

PURPOSE: Oxyntic gland neoplasm (OGN) is a rare condition that can be classified as oxyntic gland adenoma (OGA) or gastric adenocarcinoma of fundic-gland type (GA-FG). GA-FG primarily presents as early gastric cancer, with only a few reported cases of advanced gastric cancer (AGC). We aimed to investigate the clinicopathological features of OGN and describe an aggressive variant. MATERIALS AND METHODS: We investigated a total of 29 cases, including a patient with double primary cases, diagnosed with OGN or differentiated-type adenocarcinoma with GA-FG morphology, between November 2016 and April 2022. We analyzed 54 pathological specimens and reviewed their clinicopathological, endoscopic, and histological features. The lesions were reclassified as OGA or GA-FG, and immunohistochemical (IHC) staining for MUC-5AC and MUC-6 was performed on available resected GA-FG cases. RESULTS: The median patient age was 65 years and males accounted for 58.6% of patients. Most cases occurred in the body horizontally (69.0%) and on the greater curvature side cross-sectionally (48.3%). Endoscopically, type 0-IIa (41.4%) and a subepithelial tumor-like appearance (24.1%) were the most common findings. Histologically, there were 8 cases of OGA (27.6%) and 21 cases of GA-FG (72.4%). In GA-FG, MUC-6 was positive in 13 cases (81.3%), whereas MUC-5AC was positive in 8 cases (50.0%). Three cases presented as AGCs. CONCLUSIONS: Although OGNs are generally considered low-grade, they can present as AGCs and may exhibit features of lymphovascular or perineural invasion. Recognizing the clinicopathological features and accurately diagnosing OGN are important for providing adequate treatment.

Comparison of the Prognosis of Upper-Third Gastric Cancer With That of Middle and Lower-Third Gastric Cancer.

PURPOSE: Gastric cancer is one of the most common cancers in Korea, and the proportion of upper-third gastric cancers has been steadily increasing over the last two decades. This study aimed to evaluate the effect of tumor location on gastric cancer prognosis. MATERIALS AND METHODS: We retrospectively reviewed 2,466 patients who underwent gastrectomy for pathologically proven gastric cancer between January 2011 and December 2016. The patients were divided into an upper-third group (U group; n=419, 17.0%) and a middle- and lower-third group (ML group; n=2,047, 83.0%). Clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) after surgery were compared. RESULTS: The U group had more advanced disease than the ML group and a higher incidence of N3b disease for T3 (12.0% vs. 4.9%, p=0.023) and T4 tumors (33.3% vs. 17.5%, p=0.001). The 5-year RFS rate for stage III disease was marginally lower in the U group than that in the ML group (47.1% vs. 56.7%, p=0.082). The upper third location was an independent prognostic factor for both OS (hazard ratio [HR], 1.350; 95% confidence interval [CI], 1.065-1.711) and RFS (HR, 1.430; 95% CI, 1.080-1.823). CONCLUSIONS: Upper-third gastric cancer shows extensive node metastasis compared to those located more distally in ≥T3 tumors. The upper third location is an independent prognostic factor for both OS and RFS and may have an adverse impact on RFS, particularly in patients with stage III gastric cancer.

Refractory massive chylothorax following robot-assisted laparoscopic splenectomy with pericardial devascularization treated with trans-jugular intrahepatic portosystemic shunt: a case report.

The development of a chylothorax after robot-assisted laparoscopic splenectomy combined with pericardial devascularization (LSPD) is rare. The robot-assisted procedure is similar to the standard LSPD, but surgeons must remain vigilant about potential chylothorax caused by recurrence of portal hypertension in patients with cirrhosis, an event that leads to variceal bleeding in the gastric fundus or a massive chylothorax caused by a thoracic duct fistula. We report a rare case of massive chylothorax after robot-assisted LSPD and review the literature to help elucidate the mechanisms of portal hypertension after LSPD, reduce surgical complications, and improve long-term patient outcomes. After LSPD, portal pressure monitoring, coagulation function testing, and portal vein CT imaging help in excluding portal vein thromboses and ensuring appropriate anticoagulation to reduce the development of thoracic duct fistulas. If portal hypertension recurs after surgery and a high-output chylothorax develops, conservative treatment becomes ineffective. Treatment with an active trans-jugular intrahepatic portosystemic shunt (TIPS) is recommended to lower the portal pressure.

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.