Incarceration of a part of the gastric wall into the abdominal cavity in a patient with hiatal hernia and complete dislocation of the stomach (upside-down stomach).

An upside-down stomach is a rare type of hiatal hernia. An 83-year-old woman presented to the emergency room with abdominal pain and vomiting. Computed tomography revealed an upside-down stomach and the incarceration of a part of the gastric body into the abdominal cavity. Upper gastrointestinal endoscopy revealed a circular ulcer caused by gastric ischemia. Although she was discharged after 1 week of conservative therapy, she was readmitted to the hospital 1 day after discharge because of a recurrence of hiatal hernia incarceration. She underwent laparoscopic surgery 4 days after readmission and recovered successfully.

Gel immersion endoscopic mucosal resection for small gastric neoplastic lesions: A pilot study.

Gastric endoscopic mucosal resection is challenging due to the slippery mucosa, abundant blood vessels, and the presence of mucus. We developed gel immersion endoscopy to secure the visual field, even in a blood-filled gastrointestinal lumen in 2016. Clear gel with appropriate viscosity, instead of water, can prevent rapid mixture with blood and facilitate identification of the culprit vessel. We further optimized the gel for endoscopic treatment, and the resultant product, Viscoclear (Otsuka Pharmaceutical Factory) was first released in Japan in 2020. The viscosity of this gel has been optimized to maximize endoscopic visibility without compromising the ease of its irrigation. The aim of this study is to clarify the effectiveness of gel immersion endoscopic mucosal resection for small-sized early gastric neoplasms. Seven lesions in seven patients were treated by gel immersion endoscopic mucosal resection. The size of all lesions was under 10 mm. The median procedure time was 4.5 min. Intraoperative bleeding occurred in four of seven lesions immediately after snare resection and was easily controlled by endoscopic hemostatic forceps during the gel immersion endoscopy. The R0 resection rate was 100%. In conclusion, gel immersion endoscopic mucosal resection may be a straightforward, rapid, and safe technique for resecting superficial gastric neoplasms <10 mm in diameter.

Comparison of robotic versus laparoscopic total gastrectomy for gastric cancer: A single-center retrospective cohort study in a Japanese high-volume center.

BACKGROUND: Robotic-assisted surgery has become increasingly popular worldwide in recent years. This study aimed to compare the surgical outcomes of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) to figure out the advantages of RTG. METHODS: The eligible cases in this study were patients who underwent RTG or LTG for gastric adenocarcinoma at our hospital from January 2014 to December 2022. Propensity score matching (PSM) was employed to balance the underlying selection bias. Then, surgical outcomes of patients were analyzed to be compared. RESULTS: Overall, 255 patients (LTG: 178, RTG: 77) were included in this study. After PSM, 73 patients in each arm were assigned for analysis. Operation time was longer in the RTG than in the LTG (373 vs 336 min, p < 0.01). However, the RTG was associated with shorter postoperative hospital stays (8 vs 9 days, p = 0.04) and lower incidence of grade 3 or higher postoperative complications (1 % vs 11 %, p = 0.03). More lymph nodes were harvested in the RTG (59 vs 47, p < 0.01). CONCLUSIONS: Although RTG requires longer operation time, it has the potential to provide advantages to the patient such as quicker recovery, reduction in postoperative complication, or more yield number of lymph nodes. Regarding survival outcomes, further analysis with enough follow-up is needed.

Simultaneous treatment of large hiatal hernias during Roux-en-Y gastric bypass: technical considerations and outcome.

Roux-en-Y gastric bypass (RYGB) is the preferred surgical option for patients with proven gastroesophageal reflux disease and obesity grade ≥ II (BMI ≥ 35 kg/m2). Data on simultaneous treatment of larger hiatal hernias during RYGB are scarce. From 2012 until 2022, data from all consecutive patients undergoing gastric bypass procedures were collected and retrospectively analyzed. The characteristics and surgical outcomes of patients undergoing RYGB alone (RYGBa) versus RYGB with simultaneous treatment of a large hiatal hernia (RYGB-HH) were compared. Out of 573 patients who received RYGB, we identified 12 simultaneously treated for large hiatal hernia. The characteristics of RYGB-HH versus RYGBa patients were higher age (55 vs. 44 years; p = 0.004) and lower BMI (39.2 vs. 46.9 kg/m2; p = 0.001). Duration of surgery in the RYGB-HH group was longer (144 min vs. 98 min; p < 0.001), while complications > Clavien-Dindo II were similar compared to the RYGBa group (8.3 vs. 9.4%, p = 0.56). Length of stay did not differ among the groups (4 vs. 5.5 days, p = 0.051). At a median follow-up of 12 months, there was no clinical recurrence of hiatal hernia in the RYGB-HH group. Simultaneous treatment of large hiatal hernias during Roux-en-Y gastric bypass surgery prolongs operation time but seems feasible and safe in the hands of experienced surgeons.

Amino acid metabolism-related genes as potential biomarkers and the role of MATN3 in stomach adenocarcinoma: A bioinformatics, mendelian randomization and experimental validation study.

BACKGROUND: Stomach adenocarcinoma (STAD) is a major contributor to cancer-related mortality worldwide. Alterations in amino acid metabolism, which is integral to protein synthesis, have been observed across various tumor types. However, the prognostic significance of amino acid metabolism-related genes in STAD remains underexplored. METHODS: Transcriptomic gene expression and clinical data for STAD patients were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Amino acid metabolism-related gene sets were sourced from the Gene Set Enrichment Analysis (GSEA) database. A prognostic model was built using LASSO Cox regression based on the TCGA cohort and validated with GEO datasets (GSE84433, GSE84437, GSE84426). Kaplan-Meier analysis compared overall survival (OS) between high- and low-risk groups, and ROC curves assessed model accuracy. A nomogram predicted 1-, 3-, and 5-year survival. Copy number variations (CNVs) in model genes were visualized using data from the Xena platform, and mutation profiles were analyzed with "maftools" to create a waterfall plot. KEGG and GO enrichment analyses were performed to explore biological mechanisms. Immune infiltration and related functions were evaluated via ssGSEA, and Spearman correlation analyzed associations between risk scores and immune components. The TIDE database predicted immunotherapy efficacy, while FDA-approved drug sensitivity was assessed through CellMiner database. The role of MATN3 in STAD was further examined in vitro and in vivo, including amino acid-targeted metabolomic sequencing to assess its impact on metabolism. Finally, Mendelian randomization (MR) analysis evaluated the causal relationship between the model genes and gastric cancer. RESULTS: In this study, we developed a prognostic risk model for STAD based on three amino acid metabolism-related genes (SERPINE1, NRP1, MATN3) using LASSO regression analysis. CNV amplification was common in SERPINE1 and NRP1, while CNV deletion frequently occurred in MATN3. STAD patients were classified into high- and low-risk groups based on the median risk score, with the high-risk group showing worse prognosis. A nomogram incorporating the risk score and clinical factors was created to estimate 1-, 3-, and 5-year survival rates. Distinct mutation profiles were observed between risk groups, with KEGG pathway analysis showing immune-related pathways enriched in the high-risk group. High-risk scores were significantly associated with the C6 (TGF-ß dominant) subtype, while low-risk scores correlated with the C4 (lymphocyte-depleted) subtype. Higher risk scores also indicated increased immune infiltration, enhanced immune functions, lower tumor purity, and poorer immunotherapy response. Model genes were linked to anticancer drug sensitivity. Manipulating MATN3 expression showed that it promoted STAD cell proliferation and migration in vitro and tumor growth in vivo. Metabolomic sequencing revealed that MATN3 knockdown elevated levels of 30 amino acid metabolites, including alpha-aminobutyric acid, glycine, and aspartic acid, while reducing (S)-ß-Aminoisobutyric acid and argininosuccinic acid. MR analysis found a significant causal effect of NRP1 on gastric cancer, but no causal relationship for MATN3 or SERPINE1. CONCLUSION: In conclusion, the amino acid metabolism-related prognostic model shows promise as a valuable biomarker for predicting the clinical prognosis, selecting immunotherapy and drug treatment for STAD patients. Furthermore, our study has shed light on the potential value of the MATN3 as a promising strategy for combating the progression of STAD.

Expression, DNA methylation pattern and transcription factor EPB41L3 in gastric cancer: a study of 262 cases.

PURPOSE: DNA methylation prominently inactivates tumor suppressor genes and facilitates oncogenesis. Previously, we delineated a chromosome 18 deletion encompassing the erythrocyte membrane protein band 4.1-like 3 (EPB41L3) gene, a progenitor for the tumor suppressor that is differentially expressed in adenocarcinoma of the lung-1 (DAL-1) in gastric cancer (GC). METHODS: Our current investigation aimed to elucidate EPB41L3 expression and methylation in GC, identify regulatory transcription factors, and identify affected downstream pathways. Immunohistochemistry demonstrated that DAL-1 expression is markedly reduced in GC tissues, with its downregulation serving as an independent prognostic marker. RESULTS: High-throughput bisulfite sequencing of 70 GC patient tissue pairs revealed that higher methylation of non-CpGs in the EPB41L3 promoter was correlated with more malignant tumor progression and higher-grade tissue classification. Such hypermethylation was shown to diminish DAL-1 expression, thus contributing to the malignancy of GC phenotypes. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) was found to partially restore DAL-1 expression. Moreover, direct binding of the transcription factor CDC5L to the upstream region of the EPB41L3 promoter was identified via chromosome immunoprecipitation (ChIP)-qPCR and luciferase reporter assays. Immunohistochemistry confirmed the positive correlation between CDC5L and DAL-1 protein levels. Subsequent RNA-seq analysis revealed that DAL-1 significantly influences the extracellular matrix and space-related pathways. GC cell RNA-seq post-5-Aza-CdR treatment and single-cell RNA-seq data of GC tissues confirmed the upregulation of AREG and COL17A1, pivotal tumor suppressors, in response to EPB41L3 demethylation or overexpression in GC epithelial cells. CONCLUSION: In conclusion, this study elucidates the association between non-CpG methylation of EPB41L3 and GC progression and identifies the key transcription factors and downstream molecules involved. These findings enhance our understanding of the role of EPB41L3 in gastric cancer and provide a solid theoretical foundation for future research and potential clinical applications.

The EPB41L3 gene, frequently exhibiting haplotype deletions and reduced expression in gastric cancer tissues, points to its potential role as a tumor suppressor. However, tumor suppressor genes are not only influenced by genomic deletions but also by their methylation status. Our study highlights the significantly lower expression of EPB41L3 in gastric cancer compared to adjacent non-cancerous tissues across 262 patients. We also discovered that elevated non-CpG island methylation of EPB41L3 correlates strongly with tumor malignancy progression, based on the analysis of 70 paired gastric cancer samples. Moreover, we identified CDC5L as a crucial transcription factor interacting with the EPB41L3 promoter. Integrative analyses of transcriptomic and single-cell sequencing data further revealed that AREG and COL17A1 are key downstream molecules regulated by DAL-1, with their expression tightly controlled by EPB41L3 methylation and expression levels. These insights enhance our understanding of EPB41L3's role in gastric cancer and could open new avenues for targeted therapies.

Peptic Ulcer Disease among Patients Undergoing Upper Gastrointestinal Endoscopy in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

INTRODUCTION: Peptic ulcer is a common disease of gastrointestinal tract usually present with epigastric pain and discomfort. Upper gastrointestinal endoscopy is its gold standard investigation. There has been limited study on the prevalence of peptic ulcer disease among patients undergoing upper GI endoscopy especially in Nepal. Our study aimed to find the prevalence of peptic ulcer disease among patients undergoing upper GI endoscopy at our centre. METHODS: A descriptive cross-sectional study was conducted among patients undergoing upper gastrointestinal endoscopy at a tertiary care centre from October 1, 2022 to March 31, 2023. Data was retrieved from hospital records using a preformed proforma and sample size of 219 was calculated and data of 273 cases was collected using the convenience method of sampling. RESULTS: Among 273 patients, peptic ulcer disease was found in 29 (10.62%) of patients among which 28 (10.25%) had antral ulcer and only 1 (0.36%) had duodenal ulcer. CONCLUSIONS: The prevalence of peptic ulcer disease is lower in our study centre compared to other studies and further studies can be conducted on the associated risk factors and socio-demographic distribution of peptic ulcer disease.

Super-enhancer-driven ZFP36L1 promotes PD-L1 expression in infiltrative gastric cancer.

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. Despite the widespread recognition of tumor immunotherapy in treating unresectable GC, challenges, including ineffective immunotherapy and drug resistance, persist. Therefore, understanding the regulatory mechanisms of PD-L1, particularly in the context of super-enhancers (SEs) and zinc finger protein 36 ring finger protein-like 1 (ZFP36L1) RNA-binding protein, is crucial. In this study, we performed H3K27ac Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing, investigated the heterogeneity of SEs between two GC subtypes with differential growth patterns, and revealed the immune escape signatures driven by ZFP36L1-SE in infiltrative GC through SEs inhibitors treatment. The regulation of ZFP36L1 to PD-L1 was evaluated by quantitative PCR, western blot, flow cytometry, and immunohistochemistry. Furthermore, we explored its regulatory mechanisms using a combination of molecular biology techniques, including luciferase reporter assay, GST/RNA pull-down, chromatin immunoprecipitation (ChIP)/RIP experiments, and in vivo functional assays. We demonstrated that ZFP36L1, driven by an SE, enhances IFN-γ-induced PD-L1 expression, with SPI1 identified as the specific transcription factor binding to ZFP36L1-SE. Mechanistically, ZFP36L1 binds to the adenylate uridylate-rich element in the 3' untranslated region (3'UTR) of HDAC3 mRNA, exacerbating its mRNA decay, and thereby facilitating PD-L1 abnormal transcriptional activation. Collectively, our findings provide mechanistic insights into the role of the SPI1-ZFP36L1-HDAC3-PD-L1 signaling axis in orchestrating immune escape mechanisms in GC, thereby offering valuable insights into the potential targets for immune checkpoint therapy in GC management.

Significance of resected stomach measurements in postoperative delayed gastric emptying following laparoscopic pylorus-preserving gastrectomy.

PURPOSE: We investigated the relationship between the resected stomach measurements, the incidence of delayed gastric emptying (DGE), and food residue 1 year after surgery in patients who underwent laparoscopic pylorus-preserving gastrectomy (PPG). MATERIALS AND METHODS: The DGE group included 10 patients fasting due to nausea, vomiting, abdominal distension, or remnant stomach distension on radiographs; the control group included 36 patients without these symptoms. We compared the size and length of lesser and greater curvatures of the resected stomach and endoscopic findings after 1 year. RESULTS: No significant differences were observed between groups in terms of sex, body mass index, gross type, histology, tumor progression, number of dissected lymph nodes, operating time, or blood loss. The DGE group was older, had a longer postoperative stay, and showed a smaller size and shorter greater curvature of the resected stomach than the control group (p < 0.01 for all). No difference was observed in the length of the lesser curvature of the resected stomach. In addition, there were no disparities in residual food, degree and extent of gastritis, or bile reflux 1 year after gastrectomy. CONCLUSIONS: Measurements of the resected stomach suggest that preventing DGE may be achievable by removing a larger area of the greater curvature and/or stomach during laparoscopic PPG. This implies potential surgical strategy improvements for better outcomes. Further multicenter trials are needed to validate and refine techniques.

Correlation between White Globe Appearance and Clinicopathologic Characteristics in Early Gastric Cancer.

Background/Aims: Magnifying endoscopy with narrow-band imaging (ME-NBI) enables the visualization of detailed microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. White globe appearance (WGA) is a small whitish lesion with a globular shape identified during ME-NBI for early gastric cancer (EGC). This study aimed to investigate the associations between WGA, clinicopathological characteristics, and other ME-NBI findings in patients with EGC. Methods: The presence or absence of WGA in 122 patients (126 lesions) with an endoscopic diagnosis of EGC who underwent ME-NBI before endoscopic or surgical resection was prospectively collected and retrospectively analyzed. During ME-NBI, the MS and MV patterns and the presence of WGA and white opaque substances (WOS) were investigated. EGC cases were categorized as differentiated or undifferentiated type, and mucosal, submucosal, or advanced. Results: Of 126 lesions, WGA was observed in 25 (19.8%). WGA was associated with tumor size (≤2 cm [17/63, 27.0%] vs >2 cm [8/63, 12.7%]; p=0.044), histologic type (differentiated type [22/89, 24.7%] vs undifferentiated type [3/37. 8.1%]; p=0.033), and tumor location (upper third [1/11, 9.1%] vs middle third [18/58, 31.0%] and lower third [6/57, 10.5%]; p=0.017). Although WGA was observed more frequently in lesions with an oval/tubular MS pattern, a fine-network MV pattern, and the absence of WOS, the difference was not statistically significant (MS pattern, p=0.358; MV pattern, p=0.212; WOS, p=0.121, respectively). Conclusions: WGA was associated with small tumor size, differentiated-type histology, and middle-third tumor location, and was more frequently observed in lesions with an oval/tubular MS and fine-network MV patterns and the absence of WOS.

Actinidia chinensis polysaccharide interferes with the epithelial-mesenchymal transition of gastric cancer by regulating the nuclear transcription factor-κB pathway to inhibit invasion and metastasis.

OBJECTIVE: To investigate the mechanisms of the effect of Actinidia chinensis polysaccharide (ACPS) on the invasion and metastasis of gastric cancer cells. METHODS: BGC-823-Luc gastric cancer cells stably transfected with a luciferase gene were used to establish an insitutransplanted tumor mouse model. A live mouse imaging system was used to observe tumor growth, and hematoxylin and eosin staining was applied to analyze tissue histopathology. Transwell and scratch wound assays were performed to examine the invasive and migratory ability of BGC-823 cells. Immunofluorescence, confocal microscopy, immunohistochemistry, and Western blot assays were used to analyze the expressions of the nuclear transcription factor-κB (NF-κB) signaling pathway and epithelial-mesenchymal transition (EMT)-related proteins. RESULTS: ACPS significantly inhibited the growth of subcutaneously transplanted BGC-823-Luc gastric cancer tumors in nude mice and reduced inflammatory cell infiltration in tumor tissues. ACPS inhibited Epidermal Growth Factor-induced invasion, migration, and morphological changes in the cytoskeleton of BGC-823 cells. ACPS inhibited gastric cancer EMT and decreased the expression of matrix metallopeptidase 9, N-cadherin and p-NF-κB p65 in transplanted tumor tissues. ACPS inhibited the expression of matrix metalloproteinases and vascular adhesion factors in BGC-823 cells, promoted p65-NF-κB nuclear translocation, and regulated proteins associated with the NF-κB p65 pathway. CONCLUSIONS: ACPS inhibited gastric cancer invasion and metastasis both in vivo and in vitro, which evidenced the inhibition of gastric cancer EMT viaregulating the NF-κB inflammatory pathway.

Weitiao No. 3 (3) enhances the efficacy of anti-programmed cell death protein-1 immunotherapy by modulating the intestinal microbiota in an orthotopic model of gastric cancer mice.

OBJECTIVE: To explore the effects of Weitiao No. 3 (3, WD-3) on anti-programmed cell death protein-1 (PD-1) immunotherapy in gastric cancer (GC). METHODS: The intestinal microbiota was analyzed by 16S rDNA sequencing of fecal samples from three groups: healthy people (Health), GC patients (GC), and WD-3-treated GC patients (WD-3). Next, we established an orthotopic model of GC mice, which were treated with anti-PD-1, WD-3, or an inoculation of intestinal bacteria. Immune markers CD3, CD4, CD8, and forkhead box protein P3 (FOXP3), and the cell proliferation marker Ki67, were evaluated by immunohistochemistry. Cell apoptosis in GC tumors was assessed by terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling staining. Enzyme-linked immunosorbent assays (ELISAs) were performed to analyze the serum levels of the following cytokines in GC mice: tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-10, interferon (IFN)-γ, and transforming growth factor (TGF)-ß. RESULTS: Sequencing data showed that there were significant differences in the composition of the gut microbial community among the three human groups. The gut bacteria in the three groups mainly comprised the phyla Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. At the genus level, the relative abundances of Bifidobacterium and Coprococcus showed significant decreases in the GC group, and an obvious increase in the WD-3 group, compared with the Health group. Interestingly, the relative abundance of Saccharopolyspora was only detected in the WD-3 group. The results of in vivo experiments in GC mice showed that WD-3 or anti-PD-1 treatment increased the levels of CD3+, CD4+, and CD8+ T cells, but decreased the levels of FOXP3+ regulatory T cells. Furthermore, WD-3 or PD-1 antibody treatment inhibited proliferation and promoted apoptosis of GC tumor cells. ELISA analysis showed that WD-3 or PD-1 antibody treatment facilitated TNF-α, IL-2, and IFN-γ expression, while suppressing IL-6, IL-10, and TGF-ß expression. Combination therapy with WD-3 and anti-PD-1 intensified all of these effects. CONCLUSION: WD-3 enhanced the immunotherapeutic efficacy of anti-PD-1 by modulating the intestinal microbiota in an orthotopic model of GC mice.

Association of miR-499 rs3746444, miR-149 rs2292832 polymorphisms and their expression levels with helicobacter pylori-related gastric diseases and Traditional Chinese Medicine syndromes.

OBJECTIVE: To provide an objective experimental basis for the gastric mucosa pathological evolution and the transformation of different Traditional Chinese Medicine (TCM) syndromes in helicobacter pylori (H. pylori)-related gastric diseases (HPGD) patients, based on the combination of TCM syndrome differentiation, molecular biology and histopathology. METHODS: A total of 203 participants were enrolled in this study. The expressions of miR-499/miR-149 and H. pylori infection in the gastric tissues from all participants were detected. The genotyping for miR-499 rs3746444 and miR-149 rs2292832 was performed. RESULTS: In H. pylori positive subjects, the proportion of precancerous gastric lesions (PGL) in liver-stomach disharmony syndrome (LSDS) group was higher than in spleen Qi deficiency syndrome (SQDS) group (P <0.001); The proportion of gastric cancer (GC) in SQDS group was higher than in spleen-stomach damp-heat syndrome (SSDHS) group and LSDS group (all P <0.001). We also found C allele of miR-149 rs2292832 was linked to lower risk of gastric atrophy [miR-149 rs2292832 C vs T: adjusted odds ratio = 0.207; 95% confidence interval (0.043-0.989); P = 0.048]. Compared with healthy control (HC) group, the expression of miR-499 was significantly increased in GC group, while the expression of miR-149 was significantly decreased in chronic inflammation group, PGL group and GC group (all P < 0.05). Test for trend showed that GC risk was on a rising trend with the increasing expression of miR-499 and decreasing expression of miR-149 (both P for trend < 0.05). CONCLUSION: The C allele of miR-149 rs2292832 may be a protective factor for gastric mucosal atrophy. H. pylori may participate in the evolution of benign to malignant gastric mucosa lesions by inducing the overexpression of miR-499 and down regulation of miR-149. In addition, patients with H. pylori infection combined SQDS or LSDS may have higher risk of gastric mucosal malignant lesions.

Introduction of LPIN1 as a potential diagnostic and prognostic biomarker for gastric cancer via integrative bioinformatics analysis of a competing endogenous RNA network and experimental validation.

Objectives: Identification of effective biomarkers is crucial for the heterogeneous disease of gastric cancer (GC). Recent studies have focused on the role of pseudogenes regulating gene expression through competing endogenous RNA (ceRNA) networks, however, the pseudogene-associated ceRNA networks in GC remain largely unknown. The current study aimed to construct and analyze a three-component ceRNA network in GC and experimentally validate a ceRNA. Materials and Methods: A comprehensive analysis was conducted on the RNA-seq and miRNA-seq data of The Cancer Genome Atlas (TCGA) stomach adenocarcinoma (STAD) dataset to identify differentially-expressed mRNAs (DEMs), pseudogenes (DEPs), and miRNAs (DEMis). Pseudogene-associated ceRNA and protein-protein interaction (PPI) networks were constructed, and functional enrichment analyses were performed. DEMs and DEPs with degree centralities≥2 were selected for survival analysis. A ceRNA was further selected for experimental validation. Results: 10,145 DEMs, 3576 DEPs, and 66 DEMis were retrieved and a ceRNA network was then constructed by including DEMis with concurrent interactions with at least a DEM and a DEP. Functional enrichment analysis demonstrated that DEMs of the ceRNA network were significantly enriched in cancer-associated pathways. LPIN1 and WBP1L were two mRNAs showing an association with STAD patients overall survival. Expression analysis of LPIN1 showed a significant decrease in GC tumors compared to non-tumor tissues (P=0.003). Conclusion: Our research emphasizes the significant implications of ceRNA networks in the development of new biomarkers for the detection and prognosis of cancer. Further examination is necessary to explore the functional roles of LPIN1 in the pathogenesis of GC.

Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma.

BACKGROUND: Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour. METHODS: This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers. RESULTS: Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location. CONCLUSION: Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.

Machine learning based intratumor heterogeneity signature for predicting prognosis and immunotherapy benefit in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is a prevalent malignancy that is highly aggressive and heterogeneous. Intratumor heterogeneity (ITH) showed strong link to tumor progression and metastasis. High ITH may promote tumor evolution. An ITH-related signature (IRS) was created using as integrative technique including 10 machine learning methods based on TCGA, GSE15459, GSE26253, GSE62254 and GSE84437 datasets. The relevance of IRS in predicting the advantages of immunotherapy was assessed using a number of prediction scores and three immunotherapy datasets (GSE78220, IMvigor210 and GSE91061). Vitro experiments were performed to verify the biological functions of AKR1B1. The RSF + Enet (alpha = 0.1) projected model was proposed as the ideal IRS because it had the highest average C-index. The IRS demonstrated a strong performance in serving as an independent risk factor for the clinical outcome of STAD patients. It performed exceptionally well in predicting the overall survival rate of STAD patients, as seen by the TCGA cohort's AUC of 1-, 3-, and 5-year ROC curves, which were 0.689, 0.683, and 0.669, respectively. A low IRS score demonstrated a superior response to immunotherapy, as seen by a lower TIDE score, lower immune escape score, greater TMB score, higher PD1&CTLA4 immunophenoscore, higher response rate, and improved prognosis. Common chemotherapeutic and targeted treatment regimens had lower IC50 values in the group with higher IRS scores. Vitro experiment showed that AKR1B1 was upregulated in STAD and knockdown of AKR1B1 obviously suppressed tumor cell proliferation and migration. The present investigation produced the best IRS for STAD, which may be applied to prognostication, risk stratification, and therapy planning for STAD patients.

Integrative analysis of multiple cell death model for precise prognosis and drug response prediction in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a common upper gastrointestinal tumor. However, the evaluation of prognosis and treatment response in patients with gastric cancer remains a challenge. Programmed cell death (PCD) is one of the important terminal paths for the cells of metazoans, and is involved in a variety of biological events that include morphogenesis, maintenance of tissue homeostasis, and elimination of harmful cells. The objective of this project is to investigate the predictive significance of cell death pathways and create prognostic signatures associated to cell death, with the purpose of forecasting prognosis and providing guidance for the treatment of gastric cancer. METHODS: Gene transcription profiles and corresponding clinical data of gastric cancer patients were collected from The Cancer Genome Atlas (TCGA-STAD, n = 448) and the Gene Expression Comprehensive Database (GSE84437, n = 483). Thirteen types of cell death-related genes, including apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, cuprotosis, parthanatos, entotic cell death, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis, were analysed. Cell death-related genes associated with prognosis were identified in the TCGA-STAD training cohort using Lasso-Cox regression to generate a risk score. Patients were categorized into high and low-risk groups based on the median risk score for survival difference analysis. Cell death-related genes associated with prognosis were identified in the TCGA-STAD training cohort using Lasso-Cox regression to generate a risk score. Additionally, the response to immunotherapy in the high-risk and low-risk groups was calculated using the oncoPredict algorithm. Futhermore, the model genes were validated in the GEO validation set. RESULTS: A total of 324 differential programmed cell death (PCD)-related genes were identified, and 65 were selected through single-factor Cox analysis. Six PCD-related genes were ultimately identified by Lasso regression to construct a prognostic risk score model. The log-rank test revealed that patients in the high-risk group had inferior survival time compared with those in the low-risk group. The area under the ROC curve (AUC) for the training group at years 1, 3, and 5 were 0.684, 0.713, 0.743, respectively, while the AUC for the validation cohort at years 1, 3, and 5 were 0.695, 0.704, and 0.707, respectively. Unsupervised clustering identified potential subtypes included in the model, and a survival difference was also observed between the two subgroups. Multifactor Cox results, combined with clinical information, demonstrated that the prognostic risk score can serve as an independent prognostic factor, irrespective of other clinical features. CONCLUSION: By comprehensively analyzing multiple cell death patterns, we have established a novel model that accurately forecasts the clinical prognosis and drug sensitivity of gastric cancer. It was found that all 12 representative drugs may not be suitable for patients in high-risk groups.

Clinical implications of CT-detected ascites in gastric cancer: association with peritoneal metastasis and systemic inflammatory response.

OBJECTIVES: This study aimed to evaluate the diagnostic significance of computed tomography (CT) detected ascites in gastric cancer (GC) with peritoneal metastasis (PM) and investigate its association with systemic inflammatory response. METHODS: This retrospective study included 111 GCs with ascites (PM: n = 51; No PM: n = 60). Systemic inflammatory indexes, tumor markers, and the CT-assessed characteristics of ascites were collected. The differences in parameters between the two groups were analyzed. Diagnostic performance was obtained by receiver operating characteristic curve analysis. The association between the volume of ascites and clinical characteristics was evaluated with correlation analysis. RESULTS: In this study, over half of GCs with ascites were not involved with PM. The systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), five tumor markers, and the characteristics of ascites showed significant differences between the two groups (all p < 0.05). Among them, SII, NLR, PLR, and the volume of ascites achieved the areas under the curve of 0.700, 0.698, 0.704, and 0.903, respectively. Moreover, the volumes of ascites showed positive correlations with SII, NLR, and PLR in GCs with PM, and the volumes of ascites detected in the upper abdomen were more strongly correlated with CA125 level (all p < 0.05). CONCLUSION: Many GCs with CT-detected ascites did not occur with synchronous PM. The presence of upper abdominal ascites had certain clinical significance for diagnosing PM in GCs. Systemic inflammatory indexes were elevated and positively correlated with the volume of ascites in GCs with PM, which might suggest the enhanced systemic inflammatory response. CRITICAL RELEVANCE STATEMENT: CT-detected ascites in the upper abdomen played an indicative role in identifying synchronous PM in GCs, and the systemic inflammatory response was enhanced in GCs with PM, which might be helpful for clinical evaluation. KEY POINTS: Many GCs with CT-detected ascites did not occur with synchronous PM. CT-detected ascites in the upper abdomen help in identifying PM in GCs. GCs with PM showed elevated systemic inflammatory indexes and enhanced systemic inflammatory response.

Clinicopathologic Features and Outcomes of Endoscopic Submucosal Dissection for Foveolar-Type Adenocarcinoma of the Stomach.

PURPOSE: Foveolar-type adenocarcinoma of the stomach is a rare variant of gastric cancer. The clinicopathological features and outcomes of endoscopic submucosal dissection (ESD) for gastric foveolar-type adenocarcinoma remain unclear. MATERIALS AND METHODS: This study included 1,161 patients who underwent ESD for single early gastric cancers (EGCs) (78 foveolar-type adenocarcinomas and 1,083 well-differentiated [WD] adenocarcinomas). The clinicopathological features and short- and long-term outcomes of ESD for gastric foveolar-type adenocarcinomas were reviewed and compared with those for WD EGCs. RESULTS: Gastric foveolar-type adenocarcinomas were larger and more likely to exhibit an elevated macroscopic appearance than WD EGCs. Foveolar-type adenocarcinomas exhibited higher rates of lymphatic invasion, histological heterogeneity, and lateral margin involvement than WD EGCs. The en bloc R0 and curative resection rates of foveolar-type adenocarcinoma were 85.9% and 76.9%, respectively. Both foveolar-type adenocarcinoma rates were significantly lower than those of WD EGCs (95.8% and 91.3%, respectively). Lateral margin involvement accounted for 55.6% of the non-curative resection cases of foveolar-type adenocarcinoma. Among patients who underwent curative ESD for foveolar-type adenocarcinoma, no recurrence occurred during the median 62.3 months of follow-up. No lymph node metastases were detected in patients with foveolar-type adenocarcinoma who underwent additional surgery following ESD. The overall and disease-specific survival rates of patients with foveolar-type adenocarcinoma were comparable to those of patients with WD EGC. CONCLUSIONS: Gastric foveolar-type adenocarcinomas have distinct clinicopathological features among WD EGCs. Given favorable long-term outcomes after curative resection, ESD can be indicated for early gastric foveolar-type adenocarcinomas.