Gastric cancer (GC) is a highly heterogeneous disease, and the response of patients to clinical treatment varies substantially. There is no satisfactory strategy for predicting curative effects to date. We aimed to explore a new method for predicting the clinical efficacy of GC treatment based on immune variables detected via flow cytometry.

We collected 394 tumour tissues from GC patients for flow cytometry analysis and gating analysis of tumour-infiltrating immune cells (TIICs). Unsupervised consensus clusters were generated from the cohort to classify patients into different phenogroups, and their clinical characteristics were examined. The derived model was evaluated via principal component analysis and t-distributed stochastic neighbourhood embedding analysis. Kaplan-Meier's curves were used to determine the prognosis during a 920-day-long median follow-up period (interquartile range: 834-1071 days). Adjusted multivariate Cox regression analysis was used to evaluate the association of clusters with disease-free survival (DFS) and recurrence.

All patients were classified based on their TIIC profiles into the C1 (characterized by low CD45 negative cell, high lymphocyte, high neutrophil and low CD3 + T cell levels), C2 (characterized by high CD8 + CD279+ cell and low CD4+ Th and CD8+ Tc cell numbers) and C3 (characterized by high CD4 + CD25+ and Treg cell levels) phenogroups. Patients from the three clusters had varied pathologies, MMR statuses and TIIC distribution patterns (p < .05). Kaplan-Meier's analysis showed that the prognosis of C3 was inferior compared to C1 and C2 (p = .0025). Adjusted Cox proportional hazard models helped us identify that C1 and C2 exhibited a favourable factor of recurrence after surgery, compared to C3. Kaplan-Meier's analysis showed that C1 and C2 were associated with a better DFS than C3 in some GC patient subgroups.

The machine learning model developed was found to be effective model at predicting the prognosis of patients with GC and their TIIC profiles for risk stratification in clinical settings.

The optimal time to chemotherapy (TTC) in locally advanced gastric cancer (LAGC) patients treated with neoadjuvant chemotherapy (NLAGC) remains unclear.

Consecutive 524 patients with NLAGC between Jan. 2010 and Dec. 2022 were identified. Patients were categorized into three groups: TTC < 6w, 6w ≤ TTC ≤ 8w, and TTC > 8w. Survival analysis was conducted using the Cox proportional hazards model to assess the impact of TTC on gastric cancer-specific mortality (GCSM) and all-cause mortality (ACM). Cumulative competing risk curves were employed to evaluate the incidence of competing events.

Overall, 451 patients were included.Cumulative competing risk curves showed that the 3-year ACM and GCSM were significantly lower in the 6w ≤ TTC ≤ 8w group (ACM: 19.7% vs. 37.2% vs. 39.7%, GCSM: 19.7% vs. 35.2% vs. 38.8%) compared to the TTC < 6w and TTC > 8w groups. Compared to patients with 6w ≤ TTC ≤ 8w, those with TTC < 6w or >8w had an increased risk of GCSM (HR: 2.792 and HR: 2.343, respectively) and ACM (HR: 3.102 and HR: 2.719, respectively) after adjusting for confounders. Furthermore, 6w ≤ TTC ≤ 8w had later peak recurrence compared to TTC < 6w and TTC > 8w (Peak months: 9.7 vs. 4.3 vs. 3.1).

A postoperative chemotherapy timing of 6-8 weeks was associated with better survival and delayed recurrence in NLAGC patients. These findings suggest that the 6-8 week time-window should be a key timeframe for personalized postoperative adjuvant chemotherapy decisions.

The minimum number of retrieved lymph nodes for radical gastrectomy after neoadjuvant therapy remains controversial. The objective of this study was to determine the minimum threshold for retrieved lymph nodes in patients with gastric cancer after neoadjuvant therapy to accurately evaluate staging and prognosis.

Multivariate models were employed to investigate the correlation between the number of retrieved lymph nodes and survival outcomes and stage migration. The hazard ratio curves for each retrieved lymph node count compared with 1 retrieved lymph node (as a reference), including overall survival and disease-specific survival, were fitted using a LOWESS smoother, and the structural break points were determined by Chow test.

This international multicenter study analyzed the clinicopathological data of 2,490 patients with gastric cancer who underwent gastrectomy after neoadjuvant therapy. The median follow-up period for the overall population was 90.0 months, with a median of 22 retrieved lymph nodes. The study demonstrated that a greater number of retrieved lymph nodes was linked to a greater probability of detecting positive lymph nodes (odds ratio, 1.005; P = .030) as well as improved overall survival and disease-specific survival (overall survival: hazard ratio, 0.988; P < .001 and disease-specific survival: hazard ratio, 0.987; P < .001). The cutoff point analysis identified 24 as the minimum number of retrieved lymph nodes. The 5-year overall survival rate was significantly greater in the group with ≥24 retrieved lymph nodes (46.0%) compared with the group with 16-23 retrieved lymph nodes (35.3%) and the group with <16 retrieved lymph nodes group (29.3%) (P < .001). Similar trends were observed with regard to disease-specific survival. The time-dependent area under the curve analysis revealed that the group with ≥24 retrieved lymph nodes exhibited superior predictive performance for overall survival and disease-specific survival compared to the group with <24 retrieved lymph nodes, on the basis of ypN staging (overall survival: time-dependent areas under the receiver operating characteristic curve≥24, 0.71 vs time-dependent areas under the receiver operating characteristic curve<24, 0.67; disease-specific survival: time-dependent areas under the receiver operating characteristic curve≥24, 0.72 vs time-dependent areas under the receiver operating characteristic curve<24, 0.68).

The minimum number of retrieved lymph nodes for evaluation prognosis and reducing stage migration in patients with gastric cancer who undergo radical gastrectomy after neoadjuvant therapy was 24.

Many patients respond poorly to neoadjuvant chemotherapy (NACT), negatively affecting the surgical success rate. Identifying effective biomarkers and understanding the potential resistance mechanisms are urgently needed. Data of 18 patients with advanced stomach cancer who were treated with NACT categorized according to tumor regression grade into major histological response (MJHR) and nonhistological response (NHR) groups were retrospectively analyzed. Genomic signatures associated with the response to NACT were identified using whole-exome and RNA sequencing. Extraction of molecular signatures revealed increased deficient mismatch repair signature and tumor mutation levels in the NHR group. Compared to the MJHR group, the NHR group was also characterized by a greater number of copy number alterations (p = 0.08), which was further confirmed by RNA sequencing, and upregulation of aurora kinase A (AURKA) (p = 0.05) and cyclin-dependent kinase 6 (CDK6) (p = 0.049). Western blot analysis and immunohistochemical analyses further confirmed high CDK6 (p < 0.01/p < 0.0001) and AURKA (p < 0.01/p < 0.001) expression levels in the NHR group. Finally, palbociclib, an inhibitor of CDK4/6, effectively inhibited the proliferation (p < 0.05) and induced apoptosis of oxaliplatin-resistant gastric cancer cells (p < 0.01) in vitro. These findings support the potential value of AURKA and CDK6 amplification, as well as their effects on the tumor microenvironment, in predicting poor outcomes of NACT in patients with locally advanced gastric cancer. Thus, CDK4/6 inhibitors could be used to treat NACT-resistant patients with gastric cancer.

Estimating the disease burden of stomach cancer is essential to developing evidence-based prevention and treatment strategies.

To analyze the number of deaths and the temporal trends in the mortality and years of life lost (YLL) in relation to gender, age, and the impact of aging and comorbidity via non-communicable diseases on stomach cancer burden in one of the most developed regions of a transitioning country.

Mortality data of stomach cancer were collected from the Vital Statistics System of the Pudong New Area, Shanghai, China, from 2005 to 2019. The long-term trends in crude mortality rates (CMR), age-standardized mortality rates worldwide (ASMRW), and rate of YLL(YLLr) were analyzed using the Joinpoint regression program. The aging and non-aging factors affecting the mortality rate were evaluated by the decomposition method.

A total of 11,609 deaths from stomach cancer occurred from 2005 to 2019. The CMR and ASMRW of stomach cancer were 29.83/105 person-year and 12.20/105 person-year, respectively. The CMR, ASMRW, and YLLr in males were nearly twice as higher as those in females(CMR: 35.47/105 vs. 19.83/105, ASMRW: 15.64/105 vs. 7.74/105, YLLr: 378.63/105 vs. 229.13/105). The main co-morbidities involved the circulatory (24.64%) and respiratory system (20.62%). The main metastatic sites were liver (9.08%), lung (2.79%) and peritoneum (2.33%). The long-term trends in CMR and ASMRW were significantly decreasing in males, females, and the total population from 2005 to 2019. A total of 9,460 (81.48%) elderly people aged ≥ 60 years died of stomach cancer. The top three age groups with the highest CMR were ≥ 80 years, 70-79 years, and 60-69 years. The CMR and YLLr of people aged ≥ 80 years showed the largest significantly decreasing trends. The CMR caused by aging showed significantly upward trends [average annual percent changes (AAPC) 95%CI = 37.63(14.95,64.79)%, P < 0.001], which caused by non-aging factor showed significantly downward trends [AAPC 95%CI = -18.17(-22.83,-13.22)%, P < 0.001].

Age is an important factor affecting the trend of disease burden of stomach cancer. Paying attention to high-risk people may help to reduce the YLL.

The treatment of gastric cancer remains challenging, with immunotherapy serving as a critical component of the holistic approach to its treatment. The results of this study indicated that statins could decrease the serum levels of interleukin-enhancing binding factor 3 (ILF3) and programmed cell death ligand 1(PD-L1) in GC patients and improve their prognosis. Functional experiments demonstrated that simvastatin induced ferroptosis by inhibiting ILF3 in GC cells and enhanced the killing effect of activated CD8+ T cells on GC cells. The CUT&Tag assay revealed that, mechanistically, simvastatin inhibited ILF3 expression by reducing the acetylation level at residue site H3K14 in ILF3. Next-generation sequencing and Kyoto Encyclopedia of Genes and Genomes analysis revealed that ILF3 regulated PD-L1 expression through the DEPTOR/mTOR signaling pathway. Overall, simvastatin induced ferroptosis in GC cells by inhibiting ILF3 expression while promoting the activation of CD8+ T cells to augment antitumor immune responses, thereby facilitating synergistic immunotherapy.

Pembrolizumab, a PD-1 inhibitor, has shown potential for treating advanced gastric and gastroesophageal junction (GEJ) cancer. This meta-analysis evaluates its efficacy and safety, alone or combined with chemotherapy, in this population.

A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Databases including PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched up to October 31, 2024. Twelve studies comprising 4,069 patients were included. The primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included objective response rate (ORR), adverse events (AEs), and grade ≥ 3 AEs. Effect sizes were calculated using mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs).

Pembrolizumab combined with chemotherapy significantly improved OS (MD = 1.92 months; 95% CI: 0.94 to 2.91) and ORR (MD = 11.05%; 95% CI: 6.29 to 15.82) compared to chemotherapy alone. Pembrolizumab monotherapy did not show a significant effect on OS (MD = 0.24 months; 95% CI: -1.15 to 1.63) and was associated with a significant reduction in PFS (MD = -2.28 months; 95% CI: -2.85 to -1.71) compared to chemotherapy alone. For safety, pembrolizumab monotherapy significantly reduced the risk of AEs (OR = 0.68; 95% CI: 0.57 to 0.81) and grade ≥ 3 AEs (OR = 0.39; 95% CI: 0.30 to 0.51) compared to chemotherapy. Pembrolizumab combined with chemotherapy did not significantly alter the risk of AEs (OR = 1.01; 95% CI: 0.90 to 1.13) or grade ≥ 3 AEs (OR = 1.12; 95% CI: 0.99 to 1.27) compared to chemotherapy alone.

Pembrolizumab combined with chemotherapy improves survival and response rates with a manageable safety profile in advanced gastric and GEJ cancers. Monotherapy shows limited efficacy, highlighting the need for combination strategies and patient selection.

Neoadjuvant chemotherapy (NAC) has been confirmed to improve the prognosis of patients with advanced gastric cancer (AGC). However, no study has investigated whether Helicobacter pylori (HP) infection affects the postoperative survival of patients who receive NAC.

This retrospective cohort study included 307 patients with AGC who underwent laparoscopic radical gastrectomy after NAC at three hospitals in China between January 1, 2016, and April 31, 2020. Cox regression was used to assess prognostic factors for survival. Kaplan-Meier was used for survival analysis.

The HP + and the HP- group included 141 and 166 cases. The 3-year overall survival (OS) and disease-free survival (DFS) of the HP + group were significantly better than the HP- group (3-year OS: 75.9% vs. 60.2%, 3-year DFS: 70.2% vs. 52.3%; All P < 0.001). For the HP + group, ypTNM Stage III (HR, 4.00; 95% CI, 1.11-14.39; P = 0.034), NAC ≥ 4 cycles (HR, 0.43; 95% CI, 0.20-0.90; P = 0.026), and adjuvant chemotherapy (AC) ≥ 4 cycles (HR, 0.20; 95% CI, 0.09-0.48; P < 0.001) are independent prognostic factors for OS. In the cohort of HP + patients who received ≥ 4 cycles of NAC, the prognosis of patients who received ≥ 4 cycles of AC after surgery was better than that of patients who received < 4 cycles of AC (3-year OS: 92.5% vs 71.4%; P = 0.042).

Following NAC, HP + patients with AGC exhibit better prognosis than that of HP- counterparts. For potentially resectable HP + AGC patients, radical surgery following ≥ 4 cycles of NAC with ≥ 4 cycles of sequential AC might be recommended to improve survival.

Berries from the Vaccinium genus, known for their rich array of bioactive metabolites, are recognized for their antioxidant, anti-inflammatory, and anticancer properties. These compounds, including anthocyanins, flavonoids, and phenolic acids, have attracted significant attention for their potential health benefits, particularly in cancer prevention and treatment. Gastric cancer (GC), a leading cause of cancer-related deaths worldwide, remains challenging to treat, especially in its advanced stages. This study investigates the therapeutic potential of Vaccinium species in GC treatment using computational methods. RNA sequencing revealed upregulated genes associated with GC, while network pharmacology and molecular docking approaches identified strong interactions between cyanidin 3-O-glucoside (C3G), a key bioactive metabolite. Furthermore, molecular dynamics simulations of the HSP90AA1-C3G complex demonstrated stable binding and structural integrity, suggesting that C3G may inhibit HSP90AA1, a protein involved in cancer progression. These findings highlight the therapeutic potential of Vaccinium metabolites, offering a novel approach to GC treatment by targeting key molecular pathways. This research provides valuable insights into the role of berries as natural therapeutics, supporting their integration into future gastric cancer treatment strategies.

Recent research suggests that neoadjuvant chemotherapy is not effective for gastric cancer with signet ring cells.

The present study performs a scoping review of research that seeks to determine whether neoadjuvant chemotherapy is more effective than upfront surgery in the survival of locally advanced signet ring gastric adenocarcinoma.

Online databases such as Pubmed, scopus and embase were used to identify articles from the last 20 years that used survival, as an initial or secondary outcome variable, after upfront surgery or neoadjuvant chemotherapy as initial treatment in locally advanced gastric signet ring cells adenocarcinoma.

After a systematic selection process, five primary studies were selected that evaluated neoadjuvant chemotherapy compared to primary surgery.

Neoadjuvant chemotherapy does not appear to have greater benefit than initial surgery in gastric adenocarcinoma with locally advanced sign ring cells, it is necessary to define which is the most appropriate qt scheme for adenocarcinoma with sign ring cells, clinical trials type studies are required to improve the evidence. Finally, a national clinical practice guide is required as an interpretative map for the management of gastric cancer which may be appropriate as a first step to know the reality.

We elucidated the influence of sarcopenic obesity on postoperative outcomes in patients with oesophago-gastric cancer.

We conducted a systematic search on MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov to identify observational studies published from their inception to September 26, 2024. Studies involving patients who underwent radical resection for oesophago-gastric cancer and were evaluated for visceral fat mass and skeletal muscle mass through body composition were included in our analysis. The primary outcomes assessed were overall survival (OS) and postoperative complications. This protocol was registered in PROSPERO (CRD42023418403).

Ultimately, 13 studies (involving 4912 patients) were included in our qualitative and quantitative analyses. Among these studies, three were prospective cohort studies, while the remaining 10 were retrospective cohort studies. Twelve studies specifically investigated gastric cancer, while one focused on esophageal cancer. The prevalence of sarcopenic obesity ranged from 5.7% to 28.7%. Compared to the absence of sarcopenic obesity, its presence worsens OS (hazard ratio: 1.52, 95% confidence interval: 1.08-2.15, heterogeneity (I2) = 66%, certainty of the evidence: low) and increases the risk of postoperative complications (relative risk ratio: 1.88, 95% CI: 1.29-2.73, I2 = 77%, certainty of the evidence: moderate). The risk of bias in each study was deemed moderate to high.

Sarcopenic obesity worsens OS and increases the risk of postoperative complications in patients with oesophago-gastric cancer undergoing radical resection.

E3 ubiquitin ligases, crucial enzymes in the ubiquitination pathway, significantly influence the development of malignant tumors, including gastric cancer (GC), by regulating the stability of oncogenic and tumor-suppressive proteins. This study employed bioinformatics analysis of public databases alongside various experimental techniques-tissue arrays, real-time reverse-transcription polymerase chain reaction, western blot, immunofluorescence, and coimmunoprecipitation-to identify and explore the role of HECW1, a pivotal NEDD4 family E3 ubiquitin ligase, in GC progression. The results demonstrated that HECW1 is markedly overexpressed in GC tissues relative to normal gastric tissues, and its elevated expression correlates with poor prognosis in GC patients. In vitro experiments revealed that HECW1 overexpression significantly enhances the metastatic capabilities of GC cells. Mechanistically, HECW1 interacts with HIPK2 to facilitate its ubiquitination and degradation, thereby activating AKT and promoting the expression of downstream epithelial mesenchymal transition-related genes. In vivo experiments confirmed HECW1's role in promoting GC cell metastasis, highlighting the HECW1-HIPK2-AKT signaling axis as critical in GC metastasis. These findings not only elucidate a novel metastasis mechanism of GC but also suggest potential molecular targets for developing new therapeutic strategies against GC.

We carried out the meta-analysis to determine the predictive value of baseline neutrophil to lymphocyte ratio (NLR) and derived neutrophil to lymphocyte ratio (dNLR) levels in patients with gastroesophageal junction or gastric cancer (GJGC) who underwent immune checkpoint inhibitor (ICI) treatment.

Eligible articles were obtained through PubMed, the Cochrane Library, EMBASE, and Google Scholar, until April 15, 2023. The clinical outcomes evaluated in this study encompassed overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).

A total of 24 articles with 2221 patients were included in this meta-analysis. The pooled results demonstrated that patients with high NLR levels had significantly poorer OS (HR: 1.860, 95% CI: 1.564-2.213, p < 0.001) and PFS (HR: 1.678, 95% CI: 1.354-2.079, p < 0.001), and lower ORR (OR: 0.754, 95% CI: 0.621-0.915, p = 0.004) and DCR (OR: 0.391, 95% CI: 0.262-0.582, p < 0.001). Besides, we also found that high dNLR levels were significantly associated with shorter OS (HR: 2.117, 95% CI: 1.590-2.820, p < 0.001) and PFS (HR: 1.803, 95% CI: 1.415-2.297, p < 0.001).

Low baseline (Derived) NLR has the potential to predict the good efficacy of ICIs and survival outcomes in patients with GJGC. (Derived) NLR could be useful in determining the optimal treatment strategies for these patients.

Based on randomized clinical trials, this meta-analysis evaluated the efficacy and safety of intent-to-cure or prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of gastric cancer.

PubMed, Cochrane Library, Medline, and Embase databases were all systemically searched from 2004 to 2023. The quality of the study was assessed by using the Cochrane risk of bias method. The certainty of the evidence was determined by using the GRADE evaluation.

In this study, 12 articles with a total of 1181 patients were analyzed based on the inclusion criteria. The findings revealed that HIPEC had a higher survival rate (risk ratio [RR] 0.60; 95% confidence interval [CI] [0.43, 0.86], P = 0.005, RR 0.82; 95% CI [0.70, 0.97], P = 0.02, RR 0.83; 95% CI [0.71, 0.96], P < 0.01, and RR 0.63 [0.54, 0.73], P < 0.00001) after 1, 2, 3, and 5 years compared with the control group. The RR was statistically significant for 1, 2, 3, and 5 years. Furthermore, the observed overall recurrence rate for the HIPEC group was lower than control group and statistically significant (RR 0.59; 95% CI [0.50, 0.68], P < 0.0001). Higher disease-free survival rate (RR 1.42; 95% CI [1.07, 1.89], P < 0.01) was observed in the HIPEC group and statistically significant.

Gastric cancer patients treated with HIPEC have shown promising outcomes with regard to survival, recurrence, disease-free survival, and adverse reactions. However, multicenter trials with larger sample sizes consisting of different ethnicities is suggested.

Two-thirds of global cancers occur in low/middle income countries (LMIC). Northern Central America is the largest LMIC region in the Western Hemisphere and lack cancer registries to guide cancer control. We conducted a gastric cancer survival study in rural Western Honduras, characterized as having among the highest gastric cancer incidence rates in Latin America.

The cohort of incident gastric cancer diagnosed between 2002 and 2015 was studied with active follow-up with household visits. The regional gastric cancer registry was primary for case identification, with completeness examination with hospital data and national death certificates. Cox regression models were used for survival calculations.

Survival follow-up was achieved in 741/774 patients (95.7%). Household interviews were conducted in 74.1% (n = 549); 65.7% were male, median age at diagnosis was 64 years, 24.5% were <55 years; 43.9% of tumors had pyloric obstruction; 45.2%, 43.2%, and 7.3% of histology was intestinal, diffuse, and mixed, respectively. A total of 24.7% patients received treatment. The 5-year survival rates were 9.9% for both males and females, 7.7% for age <45, and 7.9% for diffuse gastric cancer. Median survival time was 4.8 months [95% confidence interval (CI), 4.2-5.6]. In the final Cox regression model including age, sex, Lauren subtype, and poverty index, only treatment was significantly associated with survival (hazard ratio = 2.43, 95% CI, 1.8-3.2).

Markedly low gastric cancer 5-year survival rates are observed in rural Central America. The majority of patients present with advanced disease and a minority have access to therapy.

The findings have implications for cancer control in the Central America LMICs and for US Latino populations. See related commentary by Riquelme and Abnet, p. 1550.

Gastrointestinal (GI) cancers, encompassing a range of malignancies within the digestive tract, present significant challenges in both diagnosis and treatment, reflecting a dire need for innovative therapeutic strategies. This article delves into the profound influence of non-histone methylation on the pathogenesis and evolution of gastrointestinal (GI) cancers. Non-histone proteins, undergoing methylation by enzymes such as Protein Arginine Methyltransferases (PRMTs) and Lysine Methyltransferases (KMTs), play pivotal roles in cellular signaling, metabolism, chromatin remodeling, and other processes crucial for cancer development. This review illuminates the complex mechanisms by which non-histone methylation affects key aspects of tumor biology, including oncogenesis, growth, proliferation, invasion, migration, metabolic reprogramming, and immune escape in GI malignancies. Highlighting recent discoveries, this work underscores the importance of non-histone methylation in cancer biology and its potential as a target for innovative therapeutic strategies aimed at improving outcomes for patients with GI cancers.

To explore whether dual-energy CT (DECT) quantitative parameters could provide analytic value for the diagnosis of patients with occult peritoneal metastasis (OPM) in advanced gastric cancer preoperatively.

This retrospective study included 219 patients with advanced gastric cancer and DECT scans. The patient's clinical data and DECT related iodine concentration (IC) parameters and effective atomic number (Zeff) were collated and analyzed among noun-peritoneal metastasis (NPM), OPM and radiologically peritoneal metastasis (RPM) groups. The predictive performance of the DECT parameters was compared with that of the conventional CT features and clinical characteristics through evaluating area under curve of the precision-recall (AUC-PR), F1 score, balanced accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Borrmann IV type diagnosed on CT and serum tumor indicator CA125 index were statistically different between the NPM and OPM groups. DECT parameters included IC, normalized IC (NIC), and Zeff of PM group were lower than the NPM group. The DECT predictive nomogram combined three independent DECT parameters produced a better diagnostic performance than the conventional CT feature Borrmann IV type and serum CA125 index in AUC-PR with 0.884 vs 0.368 vs 0.189, but similar to the combined indicator which was based on the DECT parameters, the conventional CT feature, and serum CA125 index in AUC-PR with 0.884 vs 0.918.

The lower quantitative NIC, IC ratio, and Zeff on DECT was associated with peritoneal metastasis in advanced gastric cancer and was promising to identify patients with OPM noninvasively.

The liver is a frequent site of metastasis in advanced gastric cancer (GC). Despite significant advancements in diagnostic and therapeutic techniques, the overall survival rate for patients afflicted with gastric cancer liver metastasis (GCLM) remains dismally low. Precision oncology has made significant progress in identifying therapeutic targets and enhancing our understanding of metastasis mechanisms through genome sequencing and molecular characterization. Therefore, it is crucial to have a comprehensive understanding of the various molecular processes involved in GCLM and the fundamental principles of systemic therapy to develop new treatment approaches. This paper aims to review recent findings on the diagnosis, potential biomarkers, and therapies targeting the multiple molecular processes of GCLM, with the goal of improving treatment strategies for patients with GCLM.

Gastric cancer represents a significant global health challenge due to its high mortality and incidence rates, particularly in Eastern Asia, Eastern Europe, and South America. This comprehensive review synthesizes the latest epidemiological data and explores both modifiable and non-modifiable risk factors associated with gastric cancer, aiming to delineate the multifactorial etiology of this disease. Modifiable risk factors include Helicobacter pylori infection, obesity, dietary habits, smoking and alcohol consumption, whereas nonmodifiable factors comprise genetic predispositions, age, family history and male gender. The interplay of these factors significantly impacts the risk and progression of gastric cancer, suggesting potential preventive strategies. The challenges in treating gastric cancer are considerable, largely because of the late-stage diagnosis and the heterogeneity of the disease, which complicate effective treatment regimens. Current treatment strategies involve a combination of surgery, chemotherapy, radiotherapy, and targeted therapies. The FLOT regimen (5-FU, Leucovorin, Oxaliplatin and Docetaxel) is now a standard for resectable cases in Europe and the US, showing superior survival and response rates over ECF and ECX regimens. For HER2-positive gastric cancer, trastuzumab combined with chemotherapy improves overall survival, as demonstrated by the ToGA trial. Additionally, immune checkpoint inhibitors like pembrolizumab and nivolumab offer promising results. However, the five-year survival rate remains low, underscoring the urgency for improved therapeutic approaches. Recent advancements in molecular biology and cancer genomics have begun to pave the way for personalized medicine in gastric cancer care, focusing on molecular targeted therapies and immunotherapy. This review also highlights the critical need for better screening methods that could facilitate early detection and treatment, potentially improving the prognosis. By integrating epidemiological insights with new therapeutic strategies, this article aims to thoroughly understand of gastric cancer's dynamics and outline a framework for future research and clinical management, advocating for a multidisciplinary approach to tackle this formidable disease.

Interleukin 31 (IL-31) is a proinflammatory cytokine, mainly secreted by Type II helper T cells. It signals through a heterodimeric receptor complex composed of IL-31 receptor α and oncostatin-M receptor β chain. The hallmark feature of IL-31, in its pathological role, is its ability to induce pruritus in mammals. Pruritus is a common symptom and major reason of morbidity in cancer patients, compromising their quality of life. Although, IL-31 is differentially expressed in different tumor types and could promote or inhibit cancer progression, high expression of IL-31 is a contributing factor to advanced stage tumor and severity of pruritus. The simultaneous existence of pruritus and cancer could either result from the aberrations in common proteins that co-exist in both cancer and pruritus or the therapeutic treatment of cancer could indirectly induce pruritus. Although the biology of IL-31 has predominantly been described in skin diseases such as atopic dermatitis and other inflammatory diseases, the precise role of IL-31 in the tumor biology of different cancer types remains elusive. Herein, we summarize the current understanding on the role of this cytokine in the pathogenesis of different cancers.

Trifluridine/tipiracil (FTD/TPI) is approved in third-line treatment of patients with advanced/metastatic gastric and gastroesophageal junction adenocarcinomas (aGA/GEJA). The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile.

The aim is to evaluate the efficacy and safety of FTD/TPI plus oxaliplatin with or without nivolumab in patients, with HER2 negative aGA/GEJA, unfit for triplet chemotherapy (TFOX/mFLOT regimen), in the first-line metastatic setting in comparison with the standard of care FOLFOX with or without nivolumab.

This study is a prospective randomised, open label, comparative, multicentre, phase II trial designed to include 118 patients. The primary objective is to evaluate the superiority of FTD/TPI plus oxaliplatin with or without nivolumab over FOLFOX regimen with or without nivolumab in terms of PFS in a population of patients non candidate for triplet chemotherapy. Nivolumab will be used for patients whose tumour express PD-L1 with a CPS score ≥5.

PRODIGE73-UCGI40-LOGICAN study will provide efficacy and safety data on the association of FTD/TPI plus oxaliplatin with or without nivolumab versus FOLFOX regimen with or without nivolumab in first-line palliative setting, in patients with aGA/GEJA (NCT05476796).

The relationship between hospital volume and surgical mortality is well documented. However, complete centralization of surgical care is not always feasible. The present study investigates how overall volume of upper gastrointestinal surgery at hospitals influences patient outcomes following resection for gastric adenocarcinoma.

National Cancer Database (2010-2019) patients with pathologic stage 1-3 gastric adenocarcinoma who underwent gastrectomy were identified. Three cohorts were created: low-volume hospitals (LVH) for both gastrectomy and overall upper gastrointestinal operations, mixed-volume hospital (MVH) for low-volume gastrectomy but high-volume overall upper gastrointestinal operations, and high-volume gastrectomy hospitals (HVH). Chi-squared tests were used to analyze sociodemographic factors and surgical outcomes and Kaplan-Meier method for survival analysis.

In total, 26,398 patients were identified (LVH: 20,099; MVH: 539; HVH: 5,760). The 5-year survival was equivalent between MVH and HVH for all stages of disease (MVH: 56.0%, HVH 55.6%; p = 0.9866) and when stratified into early (MVH: 69.9%, HVH: 65.4%; p = 0.1998) and late stages (MVH: 24.7%, HVH: 32.0%; p = 0.1480), while LVH had worse survival. After matching patients, postoperative outcomes were worse for LVH, but there was no difference between MVH and HVH in terms of adequate lymphadenectomy, margin status, readmission rates, and 90-day mortality rates.

Despite lower gastrectomy volume for cancer, postoperative gastrectomy outcomes at centers that perform a high number of upper gastrointestinal cancer surgeries were similar to hospitals with high gastrectomy volume. These hospitals offer a blueprint for providing equivalent outcomes to high volume centers while enhancing availability of quality cancer care.

The prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored.

We Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model's performance.

The enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram's good predictive performance and clinical utility.

Integrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible.

A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement.

The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy.

As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.

Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and identified subgroups that may experience superior outcomes. Conducted across 16 oncology centers in Turkey, this study retrospectively reviewed the clinical charts of adult patients diagnosed with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma from 2016 to 2023. This study included 111 patients (54 women, 57 men) with a median age of 58 years. The median progression-free survival (PFS) and overall survival (OS) were 11.7 months and 18.2 months, respectively, whereas the objective response rate (ORR) was 70.3%. Multivariable analyses revealed that previous curative surgery was a favorable independent prognostic factor for both PFS and OS. Conversely, an Eastern Cooperative Oncology Group performance status of 2 emerged as an adverse independent prognostic factor for OS. The safety profile of nivolumab plus chemotherapy was found to be manageable. Our findings support the use of nivolumab plus chemotherapy for the first-line treatment of Turkish patients with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. Patient selection based on clinical characteristics is crucial for optimizing treatment outcomes.

The effects of the dynamics of serum tumor markers (CA72-4, CEA, CA19-9, CA125 and AFP) before and after neoadjuvant chemotherapy (NACT) on the prognosis of gastric cancer(GC) patients remain unclear.

The training set contained 334 GC patients from Fujian Medical University Union Hospital (FJMUUH) and 113 GC patients in Qinghai University Affiliated Hospital (QhUAH) were used as an external validation set. Tumor marker regression load (ΔTMRL) indicator, including ΔCA72-4, ΔCEA, ΔCA19-9, ΔCA125, and ΔAFP, is defined as [(postNACT marker- preNACT marker)/preNACT marker]. Tumor marker regression load score (TMRLS) consists of ΔCA72-4, ΔCEA and ΔCA125. The predictive performance of the nomogram-TMRLS was evaluated using the area under the receiver operating characteristic(ROC) curve(AUC), decision curve analysis(DCA), and C-index.

Patients from FJMUUH were divided into two groups, TMRLS-low and TMRLS-high, determined by R package maxstat. Survival analysis revealed a higher 3-year overall survival(OS) in the TMRLS-low than in the TMRLS-high group. The TMRLS-high group who received postoperative adjuvant chemotherapy(AC) showed a significantly higher 3-year OS rate than those who did not. Multivariate COX regression analysis indicated that TMRLS was an independent prognostic factor for OS. A nomogram for predicting OS based on TMRLS showed a significantly higher C-index and AUC than the ypTNM stage. The above results were also found in the QhUAH external validation cohort.

TMRLS is a novel independent prognostic factor for GC who underwent NACT and a radical gastrectomy. Furthermore, the TMRLS-high group, who received postoperative AC, may achieve better survival outcomes. Notably, the predictive performance of the nomogram-TMRLS significantly outperformed that of the ypTNM stage.

Staging laparoscopy is a common diagnostic tool in gastric cancer, but its performance varies widely. The aim of this study was to gain Dutch nationwide consensus regarding the indications for and execution of staging laparoscopy in patients with gastric cancer.

All surgeons in the Netherlands specialized in gastric cancer surgery (n = 52) were asked to participate in a Delphi consensus study. The study involved an initial questionnaire with a 3-point Likert scale, an online consensus meeting, and a second questionnaire using a 2-point Likert scale (agree/disagree). Consensus was defined as 70% or more agreement among participants.

In total, 45 experts completed both questionnaires (87% response rate). Consensus was reached on the indication to perform staging laparoscopy in cT3-4 or cN + or diffuse-type gastric cancer, including Siewert type III oesophagogastric junctional cancer. The experts agreed that if preoperative scans suggest infiltration of surrounding organs (cT4), the tumour's resectability should explicitly be investigated. Consensus was also reached for a systematic peritoneal cavity inspection according to Sugarbaker's Peritoneal Cancer Index (PCI) score. All regions should be inspected routinely, although the omental bursa may be inspected on indication. Aspiration of ascites or peritoneal washing should be performed for cytology. The experts agreed that restaging laparoscopy should be performed before resection in case of progressive disease on preoperative imaging. Without progression, global inspection was considered sufficient.

The results of this Dutch nationwide Delphi consensus study exposed the variability of performing staging laparoscopy in patients with gastric cancer and provided the concept for a standardized protocol.

Accurate segmentation of gastric tumors from CT scans provides useful image information for guiding the diagnosis and treatment of gastric cancer. However, automated gastric tumor segmentation from 3D CT images faces several challenges. The large variation of anisotropic spatial resolution limits the ability of 3D convolutional neural networks (CNNs) to learn features from different views. The background texture of gastric tumor is complex, and its size, shape and intensity distribution are highly variable, which makes it more difficult for deep learning methods to capture the boundary. In particular, while multi-center datasets increase sample size and representation ability, they suffer from inter-center heterogeneity.

In this study, we propose a new cross-center 3D tumor segmentation method named Hierarchical Class-Aware Domain Adaptive Network (HCA-DAN), which includes a new 3D neural network that efficiently bridges an Anisotropic neural network and a Transformer (AsTr) for extracting multi-scale context features from the CT images with anisotropic resolution, and a hierarchical class-aware domain alignment (HCADA) module for adaptively aligning multi-scale context features across two domains by integrating a class attention map with class-specific information. We evaluate the proposed method on an in-house CT image dataset collected from four medical centers and validate its segmentation performance in both in-center and cross-center test scenarios.

Our baseline segmentation network (i.e., AsTr) achieves best results compared to other 3D segmentation models, with a mean dice similarity coefficient (DSC) of 59.26%, 55.97%, 48.83% and 67.28% in four in-center test tasks, and with a DSC of 56.42%, 55.94%, 46.54% and 60.62% in four cross-center test tasks. In addition, the proposed cross-center segmentation network (i.e., HCA-DAN) obtains excellent results compared to other unsupervised domain adaptation methods, with a DSC of 58.36%, 56.72%, 49.25%, and 62.20% in four cross-center test tasks.

Comprehensive experimental results demonstrate that the proposed method outperforms compared methods on this multi-center database and is promising for routine clinical workflows.

Gastric cancer is a prevalent and deadly malignancy, and the response to immunotherapy varies among patients. This study aimed to develop a prognostic model for gastric cancer patients and investigate immune escape mechanisms using deep machine learning and single-cell sequencing analysis. Data from public databases were analysed, and a prediction model was constructed using 101 algorithms. The high-AIDPS group, characterized by increased AIDPS expression, exhibited worse survival, genomic variations and immune cell infiltration. These patients also showed immunotherapy tolerance. Treatment strategies targeting the high-AIDPS group identified three potential drugs. Additionally, distinct cluster groups and upregulated AIDPS-associated genes were observed in gastric adenocarcinoma cell lines. Inhibition of GHRL expression suppressed cancer cell activity, inhibited M2 polarization in macrophages and reduced invasiveness. Overall, AIDPS plays a critical role in gastric cancer prognosis, genomic variations, immune cell infiltration and immunotherapy response, and targeting GHRL expression holds promise for personalized treatment. These findings contribute to improved clinical management in gastric cancer.

This study aimed to identify independent prognostic factors for gastric cancer (GC) patients after curative resection using quantitative computed tomography (QCT) combined with prognostic nutritional index (PNI), and to develop a nomogram prediction model for individualized prognosis.

This study retrospectively analyzed 119 patients with GC who underwent curative resection from January 2016 to March 2018. The patients' preoperative clinical pathological data were recorded, and all patients underwent QCT scans before and after curative resection to obtain QCT parameters: bone mineral density (BMD), skeletal muscle area (SMA), visceral fat area (VFA), subcutaneous fat area (SFA) and CT fat fraction (CTFF), then relative rate of change in each parameter (ΔBMD, ΔSMA, ΔVFA, ΔSFA, ΔCTFF) was calculated after time normalization. Multivariate Cox proportional hazards was used to establish a nomogram model that based on independent prognostic factors. The concordance index (C-index), area under the time-dependent receiver operating characteristic (ROC) curve and clinical decision curve were used to evaluate the predictive performance and clinical benefit of the nomogram model． RESULTS: This study found that ΔCTFF, ΔVFA, ΔBMD and PNI are independent prognostic factors for overall survival (OS) (hazard ratio: 1.034, 0.895, 0.976, 2.951, respectively, all p < 0.05). The established nomogram model could predict the area under the ROC curve of OS at 1, 3 and 5 years as 0.816, 0.815 and 0.881, respectively. The C-index was 0.743 (95% CI, 0.684-0.801), and the decision curve analysis showed that this model has good clinical net benefit.

The nomogram model based on body composition and PNI is reliable in predicting the individualized survival of underwent curative resection for GC patients.

Gastric cancer (GC) is one of the major malignancies threatening human lives and health. Non-SMC condensin II complex subunit D3 (NCAPD3) plays a crucial role in the occurrence of many diseases. However, its role in GC remains unexplored.

The Cancer Genome Atlas (TCGA) database, clinical samples, and cell lines were used to analyze NCAPD3 expression in GC. NCAPD3 was overexpressed and inhibited by lentiviral vectors and the CRISPR/Cas9 system, respectively. The biological functions of NCAPD3 were investigated in vitro and in vivo. Gene microarray, Gene set enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms.

NCAPD3 was highly expressed in GC and was associated with a poor prognosis. NCAPD3 upregulation significantly promoted the malignant biological behaviors of gastric cancer cell, while NCAPD3 inhibition exerted a opposite effect. NCAPD3 loss can directly inhibit CCND1 and ESR1 expression to downregulate the expression of downstream targets CDK6 and IRS1 and inhibit the proliferation of gastric cancer cells. Moreover, NCAPD3 loss activates IRF7 and DDIT3 to regulate apoptosis in gastric cancer cells.

Our study revealed that NCAPD3 silencing attenuates malignant phenotypes of GC and that it is a potential target for GC treatment.