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Frequency of delayed gastric emtpying depending on the alimentaty reconstruction (Billroth-II vs. Roux-en-Y) following pancreatoduodenectomy

ABSTRACT: Interventions: Group 1: Data collection from our pancreatic resection database (whipple procedure with Billroth-II reconstruction). Data collected: Age, BMI, diagnosis, risk factors, intraoperative characteristics, delayed gastric emptying, surgical complications, length of stay. Group 2: Data collection from our pancreatic resection database (whipple procedure with Roux-en-Y reconstruction). Data collected: Age, BMI, diagnosis, risk factors, intraoperative characteristics, delayed gastric emptying, surgical complications, length of stay. Primary outcome(s): Frequency and severity of delayed gastric emptying according to the International Study Group of Pancreatic Surgery (ISGPS) definition during the hospital stay and readmission. Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: other

DISEASE(S): Malignant Neoplasm Of Small Intestine,Ampulla Of Vater,Malignant Neoplasm Of Pancreas,Extrahepatic Bile Duct,Pancreatoduodenectomy

PROVIDER: 2432935 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [miRNA-Seq]

Project description:Introduction. Hindered by a limited understanding of the molecular mechanisms responsible for diabetic gastroenteropathy (DGE), patients are managed by symptom-based therapies. We investigated the duodenal mucosal expression of protein-coding genes and miRNAs in DGE and related these abnormalities to clinical features. Methods. mRNA and micro RNA (miRNA) expression and ultrastructure of duodenal mucosal biopsies were investigated in 39 DGE patients and 21 healthy controls. Results were analyzed in the context of diabetic phenotype and gastric emptying. Results. There were 3175 differentially-expressed genes (FDR<0.05), especially mitochondrial genes, in DGE versus controls. Several mitochondrial (mt) DNA-encoded genes (12 of 13 protein coding genes mainly involved in oxidative phosphorylation (OXPHOS), both rRNAs and 9 of 22 tRNAs) were downregulated; conversely, nuclear (n) DNA-encoded mitochondrial genes (eg, OXPHOS, TCA cycle) were upregulated in DGE. Motif analysis uncovered binding sites for transcription factors NRF1, GABPA and YY1, which regulate mitochondrial biogenesis, in the promoters of differentially expressed genes. Seventeen of 30 differentially expressed miRNAs in DGE targeted differentially expressed mitochondrial genes. Mitochondrial density was also reduced and correlated with the expression of 9 mt-DNA OXPHOS genes in DGE. Uncovered by a principal component (PC) analysis of OXPHOS genes, PC1 was significantly associated with neuropathy (P = 0.01) and with delayed gastric emptying (P < 0.05). Conclusion. In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased, respectively, associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying, and correlated with cognate miRNA expression. Together, these findings provide substantial evidence for clinically-relevant mitochondrial disturbances in DGE.

2021-03-10 | GSE151496 | GEO

ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [mRNA-Seq]

2021-03-10 | GSE151495 | GEO

Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis

Project description:Background: Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in animal models of diabetes. Human studies have also revealed loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages in full thickness gastric biopsies from gastroparesis patients. Aim: We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in full thickness gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying and symptoms. Methods: Full-thickness gastric antrum biopsies were obtained from nine DG, seven IG patients and five non-diabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1300 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity Pathway Analysis and correlations were carried out. Multiple-testing corrected p-values <0.05 were considered statistically significant. Results: 73 proteins were differentially expressed in DG, 132 proteins in IG and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway (DG FDR: 7.9x10-9; IG FDR: 6.3x10-12). In DG, properdin expression correlated with GCSI-bloating (r: -0.99, FDR: 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C zeta type and complement C2 correlated with 4 hr gastric retention (r: -0.97, FDR: 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Conclusions: Protein expression changes suggest a central role of macrophage-driven immune dysregulation and complement activation in gastroparesis.

2019-09-15 | GSE130672 | GEO

BI 456906: a dual glucagon-like peptide-1/glucagon agonist promoting bodyweight reduction

Project description:Glucagon and glucagon-like peptide-1 (GLP-1) are hormones involved in energy homeostasis. GLP-1 receptor (GLP-1R) agonism reduces food intake and delays gastric emptying, and glucagon receptor (GCGR) agonism increases energy expenditure by thermogenesis. BI 456906 is a subcutaneous, once-weekly injectable dual GLP-1R/GCGR agonist in development for the treatment of obesity or non-alcoholic steatohepatitis. Here we show that BI 456906 is a potent dual agonist with an extended half-life in human plasma. Key GLP-1R-mediated mechanisms of reduced food intake, delayed gastric emptying and improved glucose tolerance were confirmed in GLP-1R knockout mice. GCGR activity was confirmed by reduced plasma amino acids, increased hepatic expression of nicotinamide N-methyltransferase and increased energy expenditure. BI 456906 produced greater bodyweight reductions than maximally efficacious semaglutide doses and modulated gene expression, including genes involved in amino acid metabolism. BI 456906 is a potent dual agonist that produces bodyweight-lowering effects through both GLP-1R and GCGR agonism.

2022-12-09 | GSE211105 | GEO

ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY

Project description:ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY

| PRJNA636083 | ENA

ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [mRNA-Seq]

Project description:ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [mRNA-Seq]

| PRJNA636079 | ENA

ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [miRNA-Seq]

Project description:ALTERED DUODENAL MUCOSAL MITOCHONDRIAL GENE EXPRESSION IS ASSOCIATED WITH DELAYED GASTRIC EMPTYING IN DIABETIC GASTROENTEROPATHY [miRNA-Seq]

| PRJNA636082 | ENA

Ly6ChiCD62LhiLy6GhiCx3CR1low Circulating Monocyte subsets are altered in a Murine Diabetic Gastroparesis Model

Project description:Circulating monocytes (Mo) are precursors to a subset of gastric resident-muscularis-macrophages (MMs). Changes in MMs are associated with delayed gastric emptying (DGE) in diabetic gastroparesis. Investigating the dynamics of Mo in an animal model of DGE using CyTOF and computational approaches, we show a high heterogeneity within the Mo-population. In DGE mice, via unbiased clustering we identified two reduced Mo clusters which exhibit migratory phenotype (Ly6ChiCD62LhiLy6GhiCD45RhiCCR2hi-intMERTEKhi-intCx3CR1low) resembling classical-Mo (CMo-like). All markers enriched in these clusters are known to regulate cell differentiation, proliferation, adhesion, and migration. Trajectory inference analysis predicted these Mo as precursors to subsequent Mo-lineages. In gastric muscle tissue, we demonstrated an increase in the gene expression level of chemokine receptor Ccr2, suggesting possibly increased trafficking of classical monocytes. These findings contribute to better understanding of the heterogenicity of the Mo-population and establish a link between two CMo-like clusters and the development of DGE phenotype.

2025-01-06 | GSE283889 | GEO

Study of the safety of a robot assisted operation using ’da Vinci Xi’ for stomach and colorectal cancer.

Project description:Interventions: A robot assisted operation using ‘da Vinci Xi’ period of ntervention: 5 years Primary outcome(s): 1. Age, sex, height, weight, BMI, PS 2. Past medical history:Health history, operation history 3. laboratory test values 4. pathological classification associated tumor, number of lymph nodes harvested, venous invasion 5. Operative information procedure, reconstruction method, anesthesia time, surgical time, operative bleeding loss, Lymph node dissection number, completed in robot-assisted laparoscopic surgery, the reason of unsuccessful completion 6. Intraoperative and postoperative stomach cancer complication 7. Intraoperative and postoperative colorectal cancer complication 8. presence or absence of post-operation treatment and relapse, post-operation treatment of a therapeutic regimen, survival period, the start time of oral ingestion after operation, postoperative length of stay 9. The number of robot-assisted implemented, analysis of the operation time Study Design: Single arm Non-randomized

| 2639120 | ecrin-mdr-crc

TransNiDeG - The Effect of Transcutaneous Nicotine Administration on the Develop-ment of Delayed Gastric Emptying following Pancreatodudoenectomy - a randomized, placebo-controlled, double-blind, multicenter trial

Project description:Interventions: Group 1: Nicotinell 14mg/24h patch Group 2: Placebo patch Primary outcome(s): to assess the effect of transcutaneous administration of nicotine as compared to placebo on the develop-ment and severity of delayed gastric emptying (DGE) following pancreatoduodenectomy Study Design: Allocation: Randomized controlled study; Masking: Blinded (masking used); Control: placebo; Assignment: parallel; Study design purpose: treatment

| 93375 | ecrin-mdr-crc

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