-
International Journal of Molecular... Dec 2018Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers... (Review)
Review
Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment. Therefore, it is essential to determine the role of the gastrin target cell, the ECL cell, in gastric carcinogenesis. Clinical trials with gastrin antagonists could improve prognoses in those with gastrin receptor positive tumours. However, further studies on gastric carcinomas applying relative available methods and with the highest sensitivity are warranted to improve our knowledge of gastric carcinogenesis.
Topics: Carcinogenesis; Carcinoma; Cell Proliferation; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms
PubMed: 30567376
DOI: 10.3390/ijms19124109 -
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 -
Gut Feb 2018Gastric carcinoma development is triggered by . Chronic infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial...
OBJECTIVE
Gastric carcinoma development is triggered by . Chronic infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy. Our aim was to evaluate the composition of the gastric microbiota in chronic gastritis and in gastric carcinoma.
DESIGN
The gastric microbiota was retrospectively investigated in 54 patients with gastric carcinoma and 81 patients with chronic gastritis by 16S rRNA gene profiling, using next-generation sequencing. Differences in microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Associations between the most relevant taxa and clinical diagnosis were validated by real-time quantitative PCR. Predictive functional profiling of microbial communities was obtained with PICRUSt.
RESULTS
The gastric carcinoma microbiota was characterised by reduced microbial diversity, by decreased abundance of and by the enrichment of other bacterial genera, mostly represented by intestinal commensals. The combination of these taxa into a microbial dysbiosis index revealed that dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Analysis of the functional features of the microbiota was compatible with the presence of a nitrosating microbial community in carcinoma. The major observations were confirmed in validation cohorts from different geographic origins.
CONCLUSIONS
Detailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis.
Topics: Adult; Aged; Bacteria; Carcinoma; Chronic Disease; Dysbiosis; Female; Gastric Mucosa; Gastritis; Gastrointestinal Microbiome; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Nitrosation; RNA, Ribosomal, 16S; Retrospective Studies; Stomach; Stomach Neoplasms
PubMed: 29102920
DOI: 10.1136/gutjnl-2017-314205 -
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 -
BMJ Clinical Evidence Sep 2008Stomach cancer is usually an adenocarcinoma arising in the stomach, and includes tumours arising at or just below the gastro-oesophageal junction (type II and III... (Review)
Review
INTRODUCTION
Stomach cancer is usually an adenocarcinoma arising in the stomach, and includes tumours arising at or just below the gastro-oesophageal junction (type II and III junctional tumours). The annual incidence varies among countries and by sex, with about 80 cases a year per 100,000 in Japanese men, 30/100,000 in Japanese women, 18/100,000 in British men, and 10/100,000 in British women.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of radical versus conservative surgical resection? What are the effects of adjuvant chemotherapy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adjuvant chemoradiotherapy, adjuvant chemotherapy, lymphadenectomy (radical, conservative), removal of adjacent organs, and subtotal gastrectomy for resectable distal tumours.
Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Esophagogastric Junction; Gastrectomy; Humans; Stomach Neoplasms
PubMed: 19445803
DOI: No ID Found -
Archives of Pathology & Laboratory... May 2016-The diagnosis of gastric epithelial lesions is difficult in clinical practice, even with the recent developments and advances in endoscopic modalities, owing to the... (Review)
Review
CONTEXT
-The diagnosis of gastric epithelial lesions is difficult in clinical practice, even with the recent developments and advances in endoscopic modalities, owing to the diverse morphologic features of the lesions, lack of standardized diagnostic criteria, and the high intraobserver and interobserver variabilities in the nonneoplastic (regenerative)-neoplastic spectrum.
OBJECTIVE
-To provide an overview of the current concepts and unresolved issues surrounding the diagnosis of diseases in the nonneoplastic-neoplastic spectrum, and to discuss some noteworthy properties and histologic features of gastric epithelial lesions.
DATA SOURCES
-A comprehensive assessment of the medical literature on gastric epithelial lesions was performed; we also interjected our own experiences into the discussion. Sources included original studies, review articles, and textbooks related to the field.
CONCLUSIONS
-Our literature review revealed that clear cell changes and micropapillary carcinoma components in gastric carcinomas are associated with poor clinical outcomes and should hence be included in pathologic reports. Moreover, we suggest a stepwise biopsy-endoscopic resection modality for the diagnosis of borderline neoplasia-nonneoplasia cases.
Topics: Biopsy; Carcinoma; Diagnosis, Differential; Early Detection of Cancer; Education, Medical, Continuing; Endoscopic Mucosal Resection; Gastric Mucosa; Humans; Neoplasm Grading; Pathology, Clinical; Precancerous Conditions; Stomach; Stomach Diseases; Stomach Neoplasms; Terminology as Topic; Workforce
PubMed: 27128297
DOI: 10.5858/arpa.2015-0300-RA -
Medicine Mar 2021Carcinosarcoma and sarcomatoid carcinoma of the stomach are rare, malignant, and biphasic tumors with high mortality. The differential diagnosis of these 2 diseases...
RATIONALE
Carcinosarcoma and sarcomatoid carcinoma of the stomach are rare, malignant, and biphasic tumors with high mortality. The differential diagnosis of these 2 diseases remains challenging. In the present study, we present 2 cases of carcinosarcoma and sarcomatoid carcinoma of the stomach.
PATIENT CONCERNS
A 54-year-old woman was admitted with complaints of epigastric pain for 4 months, but she became serious for 10 days accompanied by melena. A 75-year-old man was admitted with complaints of epigastric pain for 1 month.
DIAGNOSIS
The female had a Borrmann type III irregular ulcerative lesion (5.0 × 4.0 × 1.0 cm) originating from the gastric antrum. The male had Borrmann type I tumor polypoid exophytic (5.0 × 4.0 × 2.0 cm) in the fundus of stomach near the cardia. Both cases were identified as malignant neoplasms by endoscopic biopsy and further confirmed by performing laparoscopic proximal gastrectomy, esophagogastrostomy, and palliative distal subtotal gastrectomy. The postoperative histopathological morphology and immunohistochemistry studies revealed sarcomatoid carcinoma for the female and gastric carcinosarcoma for the male respectively.
INTERVENTIONS
The female patient subsequently underwent laparoscopy-assisted radical distal gastrectomy for gastric cancer followed by systemic chemotherapy with oxaliplatin plus tegafur. The male patient underwent laparoscopic proximal gastrectomy and esophagogastrostomy were performed.
OUTCOMES
The female had a mixture of a little poorly-differentiated adenocarcinoma and abundant sarcomatoid spindle cell elements, and is still alive healthy up to date for 2 and a half years after surgery by phone follow-up. The male patient had both adenocarcinoma and fibrosarcoma in a single tumor, and died 1 month after the operation.
LESSONS
The present study provides insight into the clinical findings, differential diagnosis, and prognosis of carcinosarcomas and sarcomatoid carcinomas of the stomach. More cases are needed for further studies in the future.
Topics: Abdominal Pain; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinosarcoma; Chemotherapy, Adjuvant; Diagnosis, Differential; Fatal Outcome; Female; Gastrectomy; Gastric Mucosa; Gastroscopy; Humans; Image-Guided Biopsy; Laparoscopy; Male; Melena; Middle Aged; Oxaliplatin; Stomach Neoplasms; Tegafur; Treatment Outcome
PubMed: 33761637
DOI: 10.1097/MD.0000000000024697 -
International Journal of Molecular... Dec 2021Malignant tumours are traditionally classified according to their organ of origin and whether they are of epithelial (carcinomas) or mesenchymal (sarcomas) origin. By... (Review)
Review
Malignant tumours are traditionally classified according to their organ of origin and whether they are of epithelial (carcinomas) or mesenchymal (sarcomas) origin. By histological appearance the site of origin may often be confirmed. Using same treatment for tumours from the same organ is rational only when there is no principal heterogeneity between the tumours of that organ. Organ tumour heterogeneity is typical for the lungs with small cell and non-small cell tumours, for the kidneys where clear cell renal carcinoma (CCRCC) is the dominating type among other subgroups, and in the stomach with adenocarcinomas of intestinal and diffuse types. In addition, a separate type of neuroendocrine tumours (NETs) is found in most organs. Every cell type able to divide may develop into a tumour, and the different subtypes most often reflect different cell origin. In this article the focus is on the cells of origin in tumours arising in the stomach and kidneys and the close relationship between normal neuroendocrine cells and NETs. Furthermore, that the erythropoietin producing cell may be the cell of origin of CCRCC (a cancer with many similarities to NETs), and that gastric carcinomas of diffuse type may originate from the ECL cell, whereas the endodermal stem cell most probably gives rise to cancers of intestinal type.
Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma; Humans; Kidney; Kidney Neoplasms; Neoplasms; Neuroendocrine Cells; Neuroendocrine Tumors; Stomach; Stomach Neoplasms
PubMed: 34948181
DOI: 10.3390/ijms222413386 -
Esophagus : Official Journal of the... Oct 2023Esophagectomy is currently the mainstay of treatment for resectable esophageal carcinoma. Gastric grafts are the first substitutes in esophageal reconstruction.... (Review)
Review
Esophagectomy is currently the mainstay of treatment for resectable esophageal carcinoma. Gastric grafts are the first substitutes in esophageal reconstruction. According to the different tailoring methods applied to the stomach, gastric grafts can be classified as whole stomach, subtotal stomach and gastric tube. Gastric-tube placement has been proven to be the preferred method, with advantages in terms of postoperative complications and long-term survival. In recent years, several novel methods involving special-shaped gastric tubes have been proposed, which have further decreased the incidence of perioperative complications. This article will review the progress and clinical application status of different types of gastric grafts from the perspectives of preparation methods, studies of anatomy and perioperative outcomes, existing problems and future outlook.
Topics: Humans; Esophagectomy; Stomach; Carcinoma; Esophageal Neoplasms
PubMed: 37490217
DOI: 10.1007/s10388-023-01021-z -
Journal of Cancer Research and Clinical... Nov 2023As a result of the high approval dynamics and the growing number of immuno-oncological concepts, the complexity of treatment decisions and control in the area of cancers... (Review)
Review
As a result of the high approval dynamics and the growing number of immuno-oncological concepts, the complexity of treatment decisions and control in the area of cancers of the esophagus, gastroesophageal junction and stomach is constantly increasing. Since the treatment indication for PD-1 inhibitors that are currently approved in the European Union is often linked to the expression of PD-L1 (programmed cell death-ligand 1), the evaluation of tissue-based predictive markers by the pathologist is of crucial importance for treatment stratification. Even though the immunohistochemical analysis of the PD-L1 expression status is one of the best studied, therapy-relevant biomarkers for an immuno-oncological treatment, due to the high heterogeneity of carcinomas of the upper gastrointestinal tract, there are challenges in daily clinical diagnostic work with regard to implementation, standardization and interpretation of testing. An interdisciplinary group of experts from Germany has taken a position on relevant questions from daily pathological and clinical practice, which concern the starting material, quality-assured testing and the interpretation of pathological findings, and has developed recommendations for structured reporting.
Topics: Humans; B7-H1 Antigen; Biomarkers; Esophagus; Esophagogastric Junction; Carcinoma; Biomarkers, Tumor
PubMed: 37874352
DOI: 10.1007/s00432-023-05180-5