Gastric Cancer Research Articles

Plasma Metabolomic Signatures of H. pylori Infection, Alcohol Drinking, Smoking, and Risk of Gastric Cancer.

Circulating metabolic profiles have shown promising potential in identifying high-risk populations for various diseases, while metabolic perturbation plays an important role in gastric cancer. In this study, we conducted a cross-sectional study with 1800 participants to identify plasma metabolite signatures associated with environmental risk factors of gastric cancer. Subsequently, we evaluated the association between these signatures and gastric cancer risk in a nested case-control study involving 326 gastric cancer cases and 326 matched cancer-free controls. We conducted mediation analyses to elucidate the potential impact of metabolites on the association between environmental factors and gastric cancer. In the cross-sectional study, we identified 46 metabolites associated with Helicobacter pylori (H. pylori) infection, 365 with alcohol drinking, and 154 with smoking status. In the nested case-control study, 60 plasma metabolites, comprising 30 lipids, 15 amino acids, 6 xenobiotics, 3 nucleotides, 2 cofactors and vitamins, 2 carbohydrate, 1 energy, and 1 peptide, were associated with gastric cancer risk. A one-standard deviation increment in the H. pylori infection-related metabolomic signature was associated with an increased risk of gastric cancer (OR = 1.66, 95% CI: 1.32-2.09, p = 1.62 × 10-5). Furthermore, the effect of H. pylori infection on gastric cancer was partially mediated by the metabolomic signature (23.28%, 95% CI: 0.09-0.56) or adenine (13.69%, 95% CI: 0.05-0.31). In conclusion, we have identified metabolites associated with environmental factors and demonstrated the association between the H. pylori infection signature and gastric cancer risk. The findings provide novel insights into characterizing high-risk population for gastric cancer.

AKR1C3 mediates gastric cancer cell invasion and metastasis via the AKT and JNK/p-NF-κB signaling pathways

Gastric cancer (GC) is globally recognized as the fifth most common cancer and the third leading cause of cancer-related mortality. Early metastasis in GC significantly contributes to its high mortality and unfavorable prognosis. However, the underlying mechanisms of this phenomenon remain largely unexplored. Among the various factors involved, AKR1C3 has emerged as a crucial component in the pathways of tumorigenesis and metastasis across multiple cancer types. Yet, the precise significance of AKR1C3 in GC patients’ prognosis and its role in GC progression remain elusive. This study illuminated the significant downregulation of AKR1C3 in GC tissues, linking it to an aggressive phenotype and poor prognosis. Interestingly, while AKR1C3 overexpression did not affect the proliferation of GC cells, it significantly inhibited their ability to invade and metastasize. The underlying mechanism appears to involve AKR1C3’s inhibition of the p-JNK pathway, which leads to reduced phosphorylation of IKKα/β and IKBα, lowering p-NF-κB levels and hindering its movement into the nucleus, thereby stifling the epithelial-mesenchymal transition (EMT) process in GC cells. These insights reveal AKR1C3’s tumor-suppressive effects in GC and suggest its potential as a diagnostic and prognostic biomarker, offering new avenues for targeted therapies in gastric cancer management.

Nrf2 depletion enhanced curcumin therapy effect in gastric cancer by inducing the excessive accumulation of ROS

Gastric cancer (GC) is the most common malignant tumor of the gastrointestinal tract and currently has a poor clinical outcome. Turmeric’s rhizome contains a polyphenolic component called curcumin (Cur), which has been demonstrated to inhibit a variety of tumor cells, such as pancreatic, colon, lung and gastric cancers. However, it remains to be elucidated how Cur functions in GC and what molecular processes underlie it. Here, Cur showed a stronger inhibitory effect on GC cells AGS and HGC27. In addition, Cur’s inhibition of GC cells growth was accompanied by increased ROS production, triggering of the Keap1-Nrf2 signaling pathway, and increased transcription of its downstream antioxidant genes HO-1, GCLM, and NQO1. However, when a ROS scavenger NAC was used, the inhibitory effect of Cur on GC cells was reversed. Nuclear factor erythroid 2-related factor 2 (Nrf2) is overexpressed or activated in cancers to shield cancer cells from oxidative damage by responding to oxidative stress (OS). Cur has been found to act as an activator of Nrf2. Notably, compared with Nrf2 knockdown and Cur alone, the combination of the two dramatically increased Cur-induced ROS overaccumulation and inhibition of GC cells proliferation, migration, and invasive abilities. Consistent with in vitro experiments, Cur combined with Nrf2 knockdown significantly inhibited tumor growth in nude mice transplanted with AGS cells. Therefore, we concluded that Nrf2 depletion enhanced Cur therapy effect in GC by inducing the excessive accumulation of ROS, indicating that this is a promising treatment strategy.

Epstein-Barr virus infection upregulates extracellular OLFM4 to activate YAP signaling during gastric cancer progression

Extracellular vesicles (EVs) are known to mediate cell communications and shape tumor microenvironment. Compared to the well-studied small EVs, the function of large microvesicles (MVs) during tumorigenesis is poorly understood. Here we show the proteome of MVs in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC), and identify olfactomedin 4 (OLFM4) is induced by EBV infection and secreted via MVs to promote tumor progression through Hippo signaling. Specifically, OLFM4 is a target gene of the cGAS-STING pathway, and EBV infection activates cGAS-STING pathway and increases OLFM4 expression. Moreover, MV-carried OLFM4 binds with the extracellular cadherin domain of FAT1, thereby impairing its intracellular interaction with MST1 and leading to YAP activation in recipient cells. Together, our study not only reveals a regulatory mechanism though which viral infection is coupled via MVs with intercellular control of the Hippo signaling, but also highlights the OLFM4-Hippo axis as a therapeutic target for EBV-associated cancers.

Prevalence of SPOP and IDH Gene Mutations in Prostate Cancer in a Jordanian Population.

Speckle-type POZ (SPOP) is described as an essential tumor suppressor factor in gastric cancer, colorectal cancer, and prostate cancer (PCa). SPOP gene mutations were reported in primary human PCa. Isocitrate dehydrogenase-1 (IDH1) oncogene mutations were detected in gliomas, acute myeloid leukemia, some benign and malignant cartilaginous tumors, and only 1% of PCa. This study aimed to investigate the prevalence of mutations of SPOP and IDH1 genes in PCa in the Jordanian population. One hundred formalin-fixed paraffin-embedded tissue samples were collected from patients diagnosed with prostate adenocarcinoma. The obtained specimens were subjected to genomic DNA extraction, PCR amplification, and direct sequencing of exons 4, 5, 6, and 7 of the SPOP gene and exon 6 of the IDH1 gene. SPOP gene mutations were found in 17% of PCa cases, while no mutation was detected in the screened exon 6 of the IDH1 gene. Clinicopathological data demonstrated a strong correlation between prostate-specific antigen (PSA) levels and both Gleason score (GS) and the International Society of Urological Pathology (ISUP) grade group (GG). There was no significant correlation between PSA levels and age (p = 0.816) nor there were significant associations for SPOP mutational status with age (p = 0.659), PSA levels (p = 0.395), GS (p = 0.259), and ISUP GG (p = 0.424) in the tested population. The study found a strong correlation between PSA levels and both GS and ISUP GG. It also identified a high frequency (17%) of SPOP gene mutations in Jordanian Arab PCa patients, mainly in exon 7. No IDH1 mutations were detected in exon 6.

The association between oral microbiome and gastric precancerous lesions.

Gastric precancerous lesions are thought to be precursors in the occurrence and development of gastric cancer through Correa's cascade. Recent studies have investigated the association between the oral microbiome and gastric precancerous lesions. However, there has yet to be a comprehensive synthesis review of the existing literature on the relationship between oral microbiome and gastric precancerous lesions. A systematic review was conducted to characterize the literature on the association between oral microbiome and gastric precancerous lesions. The studies show that oral microbiome is dynamic in individuals with gastric precancerous lesions. Oral-derived microorganisms were colonized in the gastric precancerous lesions. Interactions between oral and gastric microbiomes affect the response of the host immunity. The abnormal proliferation of oral-associated microorganisms may be linked to the reduction of gastric acid. The present review supports the potential association between oral microbiome and gastric precancerous lesions. However, the interactions are complex and multifaceted, which require further investigation.

MoS2-Based NH3 Sensor for In Situ Helicobacter pylori Detection.

Detection of Helicobacter pylori is essential for the prevention of gastric cancer. By detecting the metabolized NH3, it was able to noninvasively reveal the state of H. pylori; however, it is still a challenge since the metabolized NH3 concentration is much lower for conventional gas sensors. Herein, we developed a MoS2-based NH3 sensor for continuous, real-time monitoring of H. pylori growth. The atomic thin layer and the all-exposed surface of MoS2 facilitate NH3 adsorption and charge transferring. A high-response NH3 sensor was prepared by surface decoration of MoS2 by depositing metal nanoparticles. The Fe-decorated MoS2 sensor outperformed with a high response of 40.9% for 5.7 ppm of NH3 at 25 ± 2 °C, low LOD (6.2 ppb), and long-term stability with a response of 12.5% for 5.7 ppm of NH3 after 5 months. The Fe-decorated MoS2 sensor was applied to the detection of H. pylori and the real-time in situ monitoring of its 92 h growth cycle. The NH3 release curve of the exponential phase during H. pylori growth was continuously monitored, and the NH3 concentration was quantified. The maximum specific rate of NH3 release was 0.195 ± 0.005 h-1, which is well-consistent with the nature of H. pylori growth. This study opens up a technological roadmap for noninvasive detection of H. pylori in the future.

An integrated machine learning framework for developing and validating a prognostic risk model of gastric cancer based on endoplasmic reticulum stress-associated genes

BackgroundGastric cancer (GC), a prevalent and deadly malignancy, demonstrates poor survival outcomes. Evidence has emerged indicating that disruptions in endoplasmic reticulum homeostasis are significantly implicated in the onset and progression of various oncological conditions. This study was designed to construct a prognostic model based on genes related to endoplasmic reticulum stress(ERS) to predict survival outcomes in patients with GC. MethodsExpression profiling data for GC samples were extracted and analyzed from TCGA-STAD, revealing 214 genes related to endoplasmic reticulum stress that show differential expression when compared with normal gastric tissue. Building on these insights, a prognostic model was formulated using data from TCGA-STAD and validated through subsequent analyses of GEO datasets. The tumor immune dysfunction and exclusion(TIDE) algorithm was applied to determine the susceptibility of individuals in high- and low-risk categories to immunotherapy. The presence of immune and stromal cells within the tumor microenvironment was assessed with the aid of the ESTIMATE algorithm. Sensitivity variations to prevalent anticancer drugs between the risk groups were evaluated using the Genomics of Drug Sensitivity in Cancer(GDSC) database, and prospective therapeutic agents were confirmed through molecular docking techniques. ResultsThirty-one endoplasmic reticulum stress (ERS)-related differentially expressed genes (DEGs) crucial for prognosis in GC were pinpointed. These DEGs were then used to construct a prognostic model and were considered as independent prognostic factors for GC patients. This risk model proved to have a good predictive performance for estimating the overall survival of these patients. The patients placed into the high-risk group showed worse results and lower sensitivity to immunotherapy. Moreover, five specific targeted therapy drugs, namely BMS-754807, Dasatinib, JQ1, AZD8055 and SB505124, produced better results in the treatment of the high-risk group of patients. ConclusionsA new molecular prognostic model associated with ERS was established and validated for GC and showed relatively good discriminative and predictive ability. This model greatly expands the collection of weapons in the armoury of prognostic analysis in GC.

Role of ATP citrate lyase and its complementary partner on fatty acid synthesis in gastric cancer

ATP citrate lyase (ACLY) and acyl-CoA short-chain synthetases 2 (ACSS2) are key enzymes in lipid metabolism. We explored the role of ACLY in gastric cancer (GC) and the effect of ACLY and ACSS2 compensation on GC growth. We used immunohistochemistry to verify the expression level of ACLY in GC, shRNA to stably knock down the expression level of ACLY in GC cells. The expression levels of lipid metabolizing enzymes were verified by qPCR and WB, and targeted lipidomics and quantification of lipid metabolism-related indicators helped us to understand the changes in lipid metabolism. Finally, subcutaneous graft tumors validate our findings from in vitro experiments. ACLY is upregulated in GC tissues, downregulation of ACLY reduced lipid accumulation and inhibited GC proliferation, migration, and invasion in vitro. ACSS2 maintains cell growth by compensatory elevation to maintain fatty acid synthesis activity in ACLY-depleted GC cells. Inhibition of ACSS2 enhanced the inhibitory effect of downregulation of ACLY on the growth of transplanted tumors in nude mice. Downregulation of ACLY inhibited GC cell growth in vitro and in vivo. ACSS2 was compensated to increase to maintain cell growth in ACLY-depleted GC cells.

AYAP1-2 contributes to bFGF-induced proliferation In gastric cancer.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths in humans worldwide. Fibroblast growth factor family (FGFs) and the Hippo signaling pathway play an important role in the epithelial-mesenchymal transition (EMT) process of GC. YAP1, a key mediator of the Hippo pathway, plays an important role in tumor genesis. Alternative splicing of human YAP1 mRNA results in two major isoforms: YAP1-1, which contains a single WW domain, and YAP1-2, which contains two WW domains, respectively. There are significant differences in post-transcriptional regulation and function. Basic FGF (bFGF) treatment promoted the EMT process of most GC cell lines, and the proliferation ability was enhanced. This process may be related to the upregulation of YAP1, the proliferation ability of GC was significantly alleviated upon YAP1 knockdown. bFGF treatment can induce EMT of GC through YAP1-2 and enhance their proliferative ability. In this process, bFGF may enhance the nuclear localization of YAP1-2.In the mouse model of intraperitoneal implantation tumorigenesis, it was shown that under the action of bFGF, the expressing YAP1-2 cell lines could form larger tumors than the expressing YAP1-1, but both of them were larger than the YAP1 knockdown. Our results show that YAP1-2 is the main subtype of bFGF-induced EMT and proliferation of GC cells.

A retrospective study of provisional outcomes of intracorporeal esophagojejunostomy versus extracorporeal anastomosis during laparoscopic total gastrectomy for gastric cancer. a single -center

Gastric cancer (GC) treatment is increasingly undergoing laparoscopic total gastrectomy (LTG) procedures. However, we conducted this research to evaluate postoperative outcomes, particularly surgical complications associated with intracorporeal and extracorporeal esophagojejunostomies using linear or circular stapling techniques following LTG for GC treatment. We aimed to compare short-term postoperative outcomes, such as surgical complications and anastomotic outcomes, between the two groups. MethodFrom January 2020 to August 2022, we conducted a retrospective analysis of data from 160 consecutive patients diagnosed with GC who received either IEJ (n = 35) or EEJ (n = 125) during LTG. We utilized the Mann–Whitney U test to ascertain the statistical significance between the two groups. For comparing categorical variables, including numbers and percentages, we employed either the Pearson chi-square test, continuity correction, or Fisher's exact test as appropriate.ResultsThe operative time was similar (IEJ: 184.57 ± 36.489 vs. EEJ: 189.22 ± 43.584; P = 0.565), however, the number of positive lymph nodes was performed more in the IEJ group (IEJ: 4.71 ± 6.114 vs. EEJ: 6.39 ± 9.067 (P = 0.305). The blood loss in the IEJ group was lower than that of the EEJ (IEJ: 73.1429.182 vs. EEJ: 100.6461.693 mL, P = 0.012). There were three anastomosis leakages in the EEJ and one in the IEJ group (EEJ, 3.2% vs. IEJ, 2.8%; P > 0.999). Anastomosis bleeding only occurred in the EEJ (EEJ 1%; P = 0.003). Although the EEJ linear stapling technique had two deaths (EEJ, 1.6%).ConclusionAlthough EEJ is frequently utilized in the linear stapling technique, research indicates that the use of IEJ minimizes the incidence of complications in LTG.

Pharmacogenomic profiling of the South Korean population: Insights and implications for personalized medicine

Adverse drug reactions (ADRs) pose substantial public health issues, necessitating population-specific characterization due to variations in pharmacogenes. This study delineates the pharmacogenomic (PGx) landscape of the South Korean (SKR) population, focusing on 21 core pharmacogenes. Whole genome sequencing (WGS) was conducted on 396 individuals, including 99 healthy volunteers, 95 patients with chronic diseases, 81 with colon cancer, 81 with breast cancer, and 40 with gastric cancer, to identify genotype-specific drug dosing recommendations. Our detailed analysis, utilizing high-throughput genotyping (HTG) of CYP2D6 and comparative data from the 1,000 Genomes Project (1 KG) and the US National Marrow Donor Program (NMDP), revealed significant pharmacogenetic diversity in core pharmacogenes such as CYP2B6, CYP2C19, CYP4F2, NUDT15, and CYP2D6. Notably, intermediate metabolizer frequencies for CYP2B6 in SKR (3.28%) were comparable to Europeans (5.77%) and East Asians (5.36%) but significantly differed from other global populations (p < 0.01). For CYP2C19, 48.74% of SKR individuals were classified as intermediate metabolizers, with the *35 allele (2.02%) being unique to SKR, the allele not observed in other East Asian populations. Additionally, the high-risk *3 allele in CYP4F2 was significantly more frequent in SKR (34.72%) than in other East Asian populations (p < 0.01). NUDT15 poor metabolizers were found in 0.76% of SKR, aligning closely with other East Asians (1.59%), while TPMT poor metabolizers were predominantly observed in Europeans and Africans, with one case in SKR. We identified significant allele frequency differences in CYP2D6 variants rs1065852 and rs1135840. Among the 72 drugs analyzed, 93.43% (n = 370) of patients required dosage adjustments for at least one drug, with an average of 4.5 drugs per patient. Moreover, 31.31% (n = 124) required adjustments for more than five drugs. These findings reveal the substantial pharmacogenetic diversity of the SKR population within the global population, emphasizing the urgency of integrating population-specific PGx data into clinical practice to ensure safe and effective drug therapies. This comprehensive PGx profiling in SKR not only advances personalized medicine but also holds the potential to significantly improve healthcare outcomes on a broader scale.

Ulva pertusa Modulated Colonic Oxidative Stress Markers and Clinical Parameters: A Potential Adjuvant Therapy to Manage Side Effects During 5-FU Regimen

One of the most used chemotherapy agents in clinical practice is 5-Fluorouracil (5-FU), a fluorinated pyrimidine in the category of antimetabolite agents. 5-FU is used to treat a variety of cancers, including colon, breast, pancreatic, and stomach cancers, and its efficacy lies in its direct impact on the patient’s DNA and RNA. Specifically, its mechanism blocks the enzymes thymidylate synthetase and uracil phosphatase, inhibiting the synthesis of uracil, which cannot be incorporated into nuclear and cytoplasmic RNA. Despite being one of the most used drugs in oncology, it is associated with several significant side effects, including inflammation of the mouth, loss of appetite, and reduction in blood cells. In our study, we examined the reduction of side effects in a 5-FU regimen administered at doses of 15 mg/kg and 6 mg/kg for 14 days in 6-week-old male Sprague-Dawley rats. On the 14th day, the rats were treated orally for 2 weeks with 100 mg/kg of Ulva pertusa, a well-known seaweed from the Ulvaceae family, which has demonstrated powerful biological properties. The administration of this green alga alleviated the side effects of 5-FU, improving several parameters including body weight, food intake, and diarrhea index. It also helped reduce side effects in the blood, kidneys, and liver. Histological and molecular analyses were conducted on serum and colon tissues from the rats, examining changes in colon structure and the release of oxidative stress markers such as iNOS, COX-2, and nitrotyrosine. Several biochemical indicators, including SOD, CAT, GSH, MDA, and ascorbic acid, were also evaluated. Overall, our data indicated Ulva pertusa to be a promising therapeutic against 5-FU’s adverse effects, therefore, it could be worthwhile to investigate the possibility of using this alga in safer cancer treatment formulations. Certainly, future preclinical and clinical studies could assess the alga’s efficacy in diverse cancer treatment regimens, exploring its role as an adjuvant therapy that may reduce chemotherapy-related toxicity without compromising therapeutic outcomes.

Knowledge, attitudes, and practices of primary caregivers of gastric cancer patients regarding postoperative dietary management

BackgroundFamily caregivers of gastric cancer (GC) patients after gastrectomy have a strong demand for nutrition knowledge. This study investigates the knowledge, attitudes, and practices (KAP) of primary caregivers of GC patients regarding postoperative dietary management.MethodsWe conducted a cross-sectional study, collecting data through questionnaire distribution. Demographic information of the respondents and KAP scores were assessed and analyzed.ResultsOf 508 included participants, majority were female (59.84%) urban residents (78.94%), aged 40–60 years (53.15%). Caretakers were primarily spouses of GC patient (50.39%) or parents (10.43%), only child (12.99%) or non-only child (24.21%). Notable percentage of poor knowledge and practice was found among participants (45.05% and 40.55%, respectively), while attitude was predominantly positive (99.41%). Correlation analysis revealed a weak positive correlation between knowledge and attitude scores (r = 0.150, P < 0.001) and negative link to practice scores (r=-0.228, P < 0.001); attitude scores were positively correlated with practice (r = 0.117, P = 0.008). Multivariate logistic regression analysis found that higher attitude scores were independently associated with higher practice scores (OR = 1.360; 95%CI, 1.223–1.513), P < 0.001), while higher knowledge scores (OR = 0.684; 95%CI, 0.575–0.815), P < 0.001), older age (OR = 0.951; 95%CI, 0.918–0.985), P = 0.005), duration of caregiving > 3 months (3–6 months (OR = 0.415; 95%CI, 0.193–0.894, P = 0.025); 6 months-1 year (OR = 0.269; 95%CI, 0.120–0.606), P = 0.002); >1 year (OR = 0.290; 95%CI, 0.120–0.705), P = 0.006), and follow-up location after patient’s surgery (OR = 0.072 (0.033–0.160), P < 0.001) were independently associated with lower practice scores.ConclusionsFamily caregivers of GC patients that participated in this study demonstrated moderate knowledge and practice, but positive attitude towards dietary management after gastrectomy.

Evaluation of the effect of Helicobacter pylori -derived OMVs and released exosomes from stomach cells treated with OMVs on the expression of genes related to the TGF-β/SMAD signaling pathway in hepatocellular carcinoma

OMVs derived from Helicobacter pylori can lead to cell transformation in gastric epithelium and cancer. Additionally, exosomes (Exos) released by host cells infected with H. pylori can significantly contribute to the development of diseases such as cancer. In this study, the effects of both Exos from AGS cells treated with H. pylori-derived OMVs on the expression of genes related to the TGF-β/SMAD signaling pathway in hepatocellular carcinoma (HCC) cells were investigated. The TGF-β/SMAD pathway is one of the most important pathways that regulate the development and progression of HCC. For this purpose, after treating HepG2 cells with H. pylori-derived OMVs (directly) and Exos from AGS cells treated with H. pylori-derived OMVs (indirectly), the expression levels of TGF-β, SMAD2, SMAD3, SMAD4, and ERK genes were analyzed using Real-time PCR. The findings showed that OMVs derived from H. pylori can significantly increase the expression of genes involved in the TGF-β signaling pathway, which can affect the aggressive behavior of HepG2 cells. Additionally, exosomes secreted from AGS cells or AGS cells treated with OMVs had no effect on changing the expression of the studied genes. Therefore, only the OMVs released from H. pylori can affect the TGF-β/SMAD signaling pathway in HCC cells.

MulitDeepsurv: Survival analysis of gastric cancer based on deep learning multimodal fusion models

MulitDeepsurv: Survival analysis of gastric cancer based on deep learning multimodal fusion models

The Burden of Gastric Cancer in Northern Central America.

Gastric cancer is the fourth leading cause of cancer-related death worldwide, with nearly one million new cases diagnosed in 2020. There is marked variation in gastric cancer incidence globally, with highest incidence rates reported in the United Nations regions of Eastern Asia, Eastern Europe, and Latin America. Although the United States is considered a low-incidence country, gastric cancer presents an important cancer disparity, with higher incidence in minoritized populations, including immigrants from high-incidence regions. The Northern Central America nations are low- and middle-income countries with a high gastric cancer incidence and large US immigrant populations. These countries lack comprehensive cancer registries, but recent GLOBOCAN-imputed gastric cancer estimates are in the range of 8 to 12/100,000 age-standardized incidence rates. Three epidemiologic studies carried out in El Salvador, Nicaragua, and Honduras demonstrate a higher than predicted burden of gastric cancer with low 5-year survival (<10%). The gastric cancer burden is projected to increase in the absence of changes to national and regional cancer control plans. Twelve evidence-based recommendations to reduce gastric cancer mortality in the Americas have recently been proposed, ranging from the "test-and-treat" Helicobacter pylori eradication strategy to endoscopic screening and surveillance programs. Translating these recommendations into a practical plan for this resource-limited setting could address the disproportionate gastric cancer burden. See related article by Peña-Galo et al., p. 1564 See related article by Ruiz de Campos et al., p. 1571 See related article by Dominguez et al., p. 1578.

Diagnostic value of artificial intelligence-based pathology diagnosis system in lymphatic metastasis of gastric cancer.

Introduction Gastric cancer remains one of the leading causes of cancer-related mortality worldwide, with lymph node metastasis (LNM) being an independent prognostic factor. However, there are still challenges in the pathological diagnosis of LNM in gastric cancer (GC). The aim of this meta-analysis is to systematically evaluate the accuracy of artificial intelligence (AI) in detecting LNM in GC from whole-slide pathological images.. Methods As of March 24, 2024, a comprehensive search for studies on the pathological diagnosis of GC LNM AI was performed in the databases of PubMed, Web of Science, Cochrane Library, and CNKI. Meta-analysis of the included data was performed using Meta-Disc 1.4, Review Manager 5.4, and Stata SE 17.0 software to calculate diagnostic metrics such as overall sensitivity and specificity. The overall diagnostic performance of the AI was assessed. Meta-regression analysis explored sources of heterogeneity. Results A total of 7 articles involving 1,669 GC patients were included. The analysis showed that AI had a sensitivity of 0.90 (95% CI: 0.84-0.94) and a specificity of 0.95 (95% CI: 0.91-0.98) for the diagnosis of GC LNM, with significant heterogeneity across studies. The area under the curve was 0.97, indicating an excellent diagnostic value. Meta-regression analysis showed that the sample size and the number of study centers contributed to the heterogeneity. Conclusion AI for diagnosing LNM in GC from whole-slide pathological images demonstrates high accuracy, offering significant clinical implications for improving diagnosis and treatment strategies.

Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer

IntroductionGastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications.MethodsWe classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH.ResultsIn the univariate survival analysis for disease-specific survival, the Epstein–Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19–5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA’s classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15–2.60], p = 0.009 and HR 1.74 [95% CI 1.06–2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial–mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30–2.77], p < 0.001) when compared with aberrant p53.ConclusionsImmunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.

Safety and feasibility of laparoscopic stomach-partitioning gastrojejunostomy combined with neoadjuvant chemotherapy followed by minimally invasive gastrectomy for resectable gastric cancer with gastric outlet obstruction.

Advanced gastric cancer with gastric outlet obstruction (GOO) causes malnutrition and medication adherence issues, leading to a poor prognosis. We developed a novel multimodal, less invasive treatment approach for gastric cancer patients with symptomatic GOO: laparoscopic stomach-partitioning gastrojejunostomy (LSPGJ) combined with neoadjuvant chemotherapy (NAC), followed by minimally invasive gastrectomy with reuse of gastrojejunostomy. This study is a retrospective analysis of the safety and feasibility of our treatment strategy. In this single-institution retrospective study, we enrolled 54 patients (NAC group, n = 26; upfront gastrectomy group, n = 28) who achieved R0 resection through a minimally invasive approach between 2007 and 2020 and evaluated their short- and long-term outcomes. After LSPGJ, the Gastric Outlet Obstruction Scoring System score significantly improved (p < 0.001). The median relative dose intensity of NAC was 88.2%. Regarding short-term outcomes, there were no differences in postoperative complications, length of postsurgical hospital stay, and adjuvant chemotherapy administration. Although overall survival and relapse-free survival showed trends toward improvement in the NAC group, these differences were not statistically significant. The cumulative incidence curve for recurrence in the NAC group was significantly lower than that of the upfront gastrectomy group (p = 0.041). Recurrence and hematogenous metastasis were significantly lower in the NAC group (p = 0.031 and 0.041, respectively) than in the upfront gastrectomy group. A forest plot revealed that NAC yielded favorable outcomes, particularly for patients with a body mass index (BMI) < 18.5kg/m2, cT4, or cN1. LSPGJ combined with NAC followed by minimally invasive gastrectomy was a safe and feasible treatment strategy for patients with advanced gastric cancer with symptomatic GOO. This procedure may contribute to the early recovery of oral intake and help maintain NAC dose intensity, potentially improving prognosis, particularly for patients with low BMI and advanced-stage disease.