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Gut Mar 2021Tumour heterogeneity represents a major obstacle to accurate diagnosis and treatment in gastric adenocarcinoma (GA). Here, we report a systematic transcriptional atlas...
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, and ) and with Wnt/β-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, 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 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.
Topics: Adenocarcinoma; Biomarkers, Tumor; Chief Cells, Gastric; Gastric Fundus; Gene Expression Profiling; Humans; Sequence Analysis, RNA; Single-Cell Analysis; Stomach Neoplasms; Transcriptome
PubMed: 32532891
DOI: 10.1136/gutjnl-2019-320368 -
Clinics in Liver Disease Aug 2020Variceal bleeding is a complication of cirrhosis that defines decompensation. Important advances in the management of gastroesophageal varices have led to a significant... (Review)
Review
Variceal bleeding is a complication of cirrhosis that defines decompensation. Important advances in the management of gastroesophageal varices have led to a significant decrease in the morbidity and mortality. Achieving these results in clinical practice is contingent on clinicians applying the best practice strategies and appropriate referral to a tertiary center. Several quality metrics were developed by the American Association for the Study of Liver Diseases. This article aims to update outpatient and inpatient strategies to include the latest recommendations on variceal screening and surveillance, primary and secondary prophylaxis of variceal bleeding, and therapy for patients with acute variceal bleeding.
Topics: Adrenergic beta-Antagonists; Ambulatory Care; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastric Fundus; Gastrointestinal Hemorrhage; Hospitalization; Humans; Ligation; Liver Cirrhosis; Secondary Prevention
PubMed: 32620275
DOI: 10.1016/j.cld.2020.04.011 -
World Journal of Gastroenterology Jul 2018A depressed lesion was found at a gastric angle of 76-year-old Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a infection but no... (Review)
Review
A depressed lesion was found at a gastric angle of 76-year-old Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection (ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-I, diffusely MUC6, and scattered H/K ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type (GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, ., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.
Topics: Adenocarcinoma; Aged; Biopsy; Carcinoma, Signet Ring Cell; Endoscopic Mucosal Resection; Female; Gastric Fundus; Gastric Mucosa; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Narrow Band Imaging; Stomach Neoplasms
PubMed: 30018486
DOI: 10.3748/wjg.v24.i26.2915 -
Revista Espanola de Enfermedades... Mar 2018Both submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR) are effective methods for gastric fundus submucosal tumors (SMTs).... (Comparative Study)
Comparative Study
AIM
Both submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (EFTR) are effective methods for gastric fundus submucosal tumors (SMTs). However, there is little data that compares the two methods. The aim of this study was to compare the safety and efficacy of STER and EFTR for the treatment of SMTs in the gastric fundus.
METHODS
Clinical data was retrospectively collected from patients with gastric fundus SMTs who underwent STER or EFTR at our hospital from April 2011 to May 2016. Epidemiological data (gender, age), tumor size, procedure-related parameters, complications, postoperative hospital stay, cost and follow-up data were compared.
RESULTS
A total of 43 patients were enrolled: 15 underwent STER and the remaining 28 cases underwent EFTR. There were no significant differences between the two groups with regard to gender, age, tumor size, en bloc resection rate, operation time, pathohistological results and cost (p > 0.05). However, patients who underwent EFTR had a longer suture time, required a larger number of clips for closure and a prolonged postoperative hospital stay (p < 0.05). No recurrence was noted in either the STER or the EFTR group during a mean follow-up of 12.1 and 22.8 months, respectively.
CONCLUSIONS
The treatment efficacy of STER and EFTR for the treatment of gastric fundus SMTs was comparable. However, STER has some advantages over EFTR in terms of suture time, the number of clips required for closure and postoperative hospital stay.
Topics: Adult; Aged; Endoscopic Mucosal Resection; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Gastric Fundus; Gastric Mucosa; Humans; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 29284271
DOI: 10.17235/reed.2017.4699/2016 -
Nature Jan 2017Despite 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...
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/β-catenin signalling in mouse embryos led to conversion of fundic to antral epithelium, and that β-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.
Topics: Animals; Body Patterning; Cell Differentiation; Cell Lineage; Drug Discovery; Epithelial Cells; Epithelium; Female; Gastric Fundus; Homeodomain Proteins; Humans; Male; Mice; Organoids; Parietal Cells, Gastric; Pluripotent Stem Cells; SOXB1 Transcription Factors; Spheroids, Cellular; Trans-Activators; Wnt Proteins; Wnt Signaling Pathway; beta Catenin
PubMed: 28052057
DOI: 10.1038/nature21021 -
Surgical Pathology Clinics Sep 2020This review provides an overview of different types of gastric epithelial polyps. The polyps are classified based on their cell or epithelial compartment of origin. Some... (Review)
Review
This review provides an overview of different types of gastric epithelial polyps. The polyps are classified based on their cell or epithelial compartment of origin. Some of these polyps can be considered reactive or nonneoplastic, whereas others are neoplastic in origin, are sometimes associated with a hereditary polyposis/cancer syndrome, and may have malignant potential. The aim of this review is to provide a pragmatic overview for the practicing pathologist about how to correctly diagnose and deal with gastric epithelial polyps and when (not) to ponder, and when (not) to panic.
Topics: Adenomatous Polyps; Biopsy; Diagnosis, Differential; Gastric Fundus; Humans; Prognosis; Stomach; Stomach Neoplasms
PubMed: 32773193
DOI: 10.1016/j.path.2020.05.004 -
Journal of Laparoendoscopic & Advanced... Nov 2020Laparoscopic sleeve gastrectomy (LSG) is currently the most performed bariatric procedure worldwide. We have developed a modification to the usual surgical technique of...
Laparoscopic sleeve gastrectomy (LSG) is currently the most performed bariatric procedure worldwide. We have developed a modification to the usual surgical technique of LSG by adding a Nissen fundoplication. Provide the technical details of this new bariatric procedure. The first step of the N-sleeve technique involves dissection and reduction within the abdominal cavity of a possible hiatal hernia and closure of the hiatal orifice. A short 3 cm Nissen valve is created to maintain a gastric fundus as small and functional as possible. After that, the stapling process begins and continues in a standard pattern until the level of the previously created valve. Stapling the stomach around the valve must maintain its natural position and preserve vascularization. The following are the five major technical tips: avoid thermic injuries of the gastric wall during short gastric vessel dissection; gently handle the gastric fundus during fundoplication; take the anterior and superior part of the fundus to create the wrap 4 cm from the His angle to avoid a wrong pathway for the food (the food should not go through the wrap); check the good pathway for the food at the end of the operation with the tube by moving it through the esophagogastric junction. N-sleeve is a new procedure, technically more challenging than standard LSG, but in our experience, it seems to show similar outcomes in terms of weight loss, effects on comorbidities, and lower rate of leak and gastroesophageal reflux disease.
Topics: Esophagogastric Junction; Fundoplication; Gastrectomy; Gastric Fundus; Gastroesophageal Reflux; Hernia, Hiatal; Humans; Laparoscopy; Male; Obesity, Morbid; Weight Loss
PubMed: 32955993
DOI: 10.1089/lap.2020.0651 -
Gut and Liver Mar 2019Fundic gland polyps (FGPs), hyperplastic polyps (HPs), and xanthomas (XTs) are common benign gastric lesions that can be diagnosed by endoscopic appearance alone in most...
BACKGROUND/AIMS
Fundic gland polyps (FGPs), hyperplastic polyps (HPs), and xanthomas (XTs) are common benign gastric lesions that can be diagnosed by endoscopic appearance alone in most cases. The aim of this study was to evaluate associations between gastric cancer and these benign lesions.
METHODS
Two expert endoscopists reviewed a series of gastroscopy images. FGPs, HPs, and XTs were diagnosed by endoscopic appearance, whereas all gastric cancers were confirmed pathologically.
RESULTS
Of the 1,227 patients reviewed, 114 (9.3%) had a concurrent or past history of gastric cancer. The overall prevalences of FGPs, HPs and XTs were 9.4%, 6.3% and 14.2%, respectively. HPs and XTs coexisted in 1.6% of patients, whereas other combinations were rarer. XTs were observed in 39.3% and 11.5% of patients with and without gastric cancer, respectively (p<0.001). In contrast, no gastric cancer patients had FGPs, whereas 10.4% of patients without cancer had FGPs (p<0.001). The prevalence of HPs was similar between the two groups (8.8% and 6.0% of patients with and without cancer, respectively, p=0.29). Multivariate and Mantel-Haenszel analyses demonstrated that XTs were positively associated and FGPs were negatively associated with gastric cancer.
CONCLUSIONS
XTs and FGPs might be useful as endoscopic risk indicators for monitoring gastric cancer.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Gastric Fundus; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Humans; Hyperplasia; Japan; Male; Middle Aged; Multivariate Analysis; Polyps; Prevalence; Risk Factors; Stomach Diseases; Stomach Neoplasms; Xanthomatosis; Young Adult
PubMed: 30600671
DOI: 10.5009/gnl17136 -
Revista de Investigacion Clinica;... 2018The prevalence of gastric polyps varies around the world reflecting regional associations. We describe demographic features of patients with gastric polyp diagnosis...
BACKGROUND
The prevalence of gastric polyps varies around the world reflecting regional associations. We describe demographic features of patients with gastric polyp diagnosis treated between 1980 and 2016 at a referral center in Mexico City and analyzed trends of polyp subtype.
MATERIALS AND METHODS
We conducted a blind review of archival slides of gastric biopsies with polyp diagnosis from the years 1980, 1990, 2000, 2010, and 2016. Initial diagnosis; patient's gender, age and symptoms; and number and location of lesions were recorded. Blind slide review and trend analysis were performed.
RESULTS
In 3887 gastric biopsies, 192 patients (4.93%) with epithelial polyps were identified. The median age of patients was 58 years; 73% were female. Polyps were single in 143/192 cases (74.4%), almost 67% in the oxyntic mucosa, and 85% were associated with dyspepsia. The prevalence was 0.5%, 1.6%, 1.9%, 4.6%, and 9.6% for the years 1980, 1990, 2000, 2010, and 2016, respectively, resulting in a rising trend in the prevalence of epithelial polyps of 380% in 46 years. Fundic gland polyps (FGPs) had a global frequency of 66.6% (128/192). They were identified for the first time in the third period of the study, with a frequency of 28.6% (6/21), 66.6% (35/53), and 78.3% (87/111) for the years 2000, 2010, and 2016, respectively. Contrary, hyperplastic polyps (HPs) decreased 20%. A relative prevalence of 3.29%, 0.97%, and 0.15% was observed for FGP, HP, and gastric adenoma, respectively.
DISCUSSION
The 1400% change of FGP explains the increased prevalence of gastric polyps. Chronic treatment with proton pump inhibitors and Helicobacter pylori eradication are possible explanations.
Topics: Adenoma; Adult; Aged; Aged, 80 and over; Biopsy; Dyspepsia; Female; Gastric Fundus; Humans; Male; Mexico; Middle Aged; Polyps; Prevalence; Stomach Neoplasms; Young Adult
PubMed: 29513301
DOI: 10.24875/RIC.17002430 -
Internal Medicine (Tokyo, Japan) Oct 2017
Topics: Gastric Fundus; Humans; Mucous Membrane; Polyps; Proton Pump Inhibitors
PubMed: 28924120
DOI: 10.2169/internalmedicine.8657-16