Gastric Cancer

Additional gastrectomy is recommended after noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) despite the low incidence of lymph node metastasis (LNM). The eCura system, W-eCura score, and 11-point score reportedly predict LNM risk; however, their comparative performance remains unclear. We aimed to externally validate and directly compare five risk stratification approaches in patients with noncurative ESD. We retrospectively evaluated 634 consecutive patients with EGC who underwent noncurative ESD at a single high-volume center. Five prediction models were evaluated: the eCura system (7-point score and three-risk classification), W-eCura score (7-point score and three-risk classification), and 11-point score. All pathological findings were re-evaluated by an outcome-blinded expert pathologist. Model performance was assessed by discrimination, calibration, and decision-curve analysis (DCA). LNM was identified in 26 (4.9

Sarcopenia is an important prognostic factor in gastrointestinal malignancies, but CT-based definitions vary. This study evaluated recently published computed tomography (CT)-based cut-offs for skeletal muscle index (SMI) and psoas muscle thickness normalized to height (PMTH), derived from a young, presumably healthy reference population according to recommendations of the European Working Group on Sarcopenia in Older People (EWGSOP), in patients undergoing surgery for gastric cancer. This retrospective, single-center cohort study included patients who underwent surgery for gastric cancer between 2013 and 2018. Preoperative CT was used to assess SMI and PMTH. The recently published reference cut-offs were compared with the established definitions of Prado et al. (SMI) and Gu et al. (PMTH). Overall survival (OS) and recurrence-free survival (RFS) were the primary and secondary endpoints, respectively. Data from 212 patients with complete 5-year follow-up were analyzed. The reference cut-offs significantly discriminated OS and RFS (SMI, both p < 0.001; PMTH, both p = 0.002), whereas the established cut-offs showed weaker or no discrimination. Patients with both low SMI and low PMTH had the worst OS and RFS (both p < 0.001). Combined low SMI and low PMTH was associated with worse OS in univariable analysis (HR 2.57, 95

Marked differences in advanced gastric cancer (AGC) surgical outcomes have historically been documented between Eastern and Western centers. This study compared laparoscopic gastrectomy (LG) surgical outcomes for AGC between Japanese and Italian institutions. This international, retrospective cohort study included patients undergoing LG for AGC at 17 Italian (within the Italian Research Group for Gastric Cancer) and 5 Japanese institutions (2015–2022). Propensity score matching (PSM) was used to balance baseline characteristics. The primary endpoint was 90-day severe morbidity (Clavien-Dindo ≥ III). Secondary endpoints were 90-day mortality, R0 resection rates, and lymph node (LN) yield. Multivariable regression identified predictors of severe morbidity. From 1,617 patients, PSM selected 566 cases (283 per group). The Italian group (IG) showed a trend toward higher 90-day severe morbidity (14.8

Immune checkpoint inhibitors (ICIs) improve survival in advanced gastric cancer (GC), yet predicting therapeutic benefit versus toxicity remains challenging. Elevated interleukin-6 (IL-6) is linked to poor prognosis, but whether it simultaneously influences immune-related adverse events (irAEs) and how this relationship impacts survival remains unclear. We retrospectively analyzed 244 patients with advanced GC treated with ICIs. Predictors of high-grade irAEs were evaluated using Firth’s penalized logistic regression to mitigate small-sample bias. Independent prognostic factors for overall survival (OS) were identified via multivariable Cox analysis and validated using propensity score matching (PSM). Causal mediation analysis was performed to assess whether the effect of IL-6 on OS was mediated through irAEs. Biological mechanisms were explored using TCGA-STAD transcriptomic data. Baseline IL-6 was a strong independent predictor of high-grade irAEs (OR = 2.74, P < 0.001) and inferior OS (P = 0.019), a finding confirmed after PSM. Mediation analysis did not demonstrate a statistically significant mediating effect of irAEs on the relationship between IL-6 and survival. Bioinformatic validation linked high IL-6 expression to hyper-inflammatory signaling (TNF/IL-17 pathways) and immunosuppressive M2 macrophage infiltration. Baseline IL-6 was independently associated with both severe immune-related toxicity and inferior overall survival, suggesting that elevated systemic IL-6 reflects an adverse inflammatory state in which toxicity does not necessarily correspond to improved therapeutic outcomes. These findings support further evaluation of IL-6 in risk stratification and warrant prospective investigation into its potential therapeutic modulation in combination with ICIs.

Perineural invasion (PNI) is an established adverse prognostic factor in gastric cancer, but whether its prognostic effect varies with nodal burden and first metastatic site remains unclear. We retrospectively analyzed 12,898 patients with stage I-III gastric cancer who underwent curative-intent R0 gastrectomy at Fudan University Shanghai Cancer Center between 2000 and 2022. Multivariable Cox models with a pre-specified PNI-by-positive-node interaction estimated associations with overall survival (OS) and progression-free survival (PFS). First distant metastatic site was evaluated using Fine-Gray and Firth logistic site-contrast models. The PNI-nodal-burden association was assessed in an independent pathology cohort and the ACRG cohort. Each additional positive lymph node attenuated the PNI-associated hazard ratio for OS (interaction HR, 0.976) and PFS (interaction HR, 0.977; both interaction P < 0.001). PNI was independently associated with poorer OS (HR, 1.38; 95

Mismatch-repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastroesophageal adenocarcinoma (GEA) is associated with favorable prognosis but limited benefit from perioperative chemotherapy. Although immune checkpoint inhibition (ICI)-based approaches have shown promising activity in early-phase studies, the optimal therapeutic combinations and the feasibility of non-operative management (NOM) in resectable disease remain unclear. This exploratory, retrospective, multicenter, real-world study included 55 patients with resectable dMMR/MSI-H GEA, who were divided into subgroups, characterized and compared according to treatment strategy (chemotherapy, chemoimmunotherapy, immunotherapy and initial resection). Pathological and clinical complete response (pCR, cCR), progression-free (PFS) and overall survival (OS) were evaluated. Patients received chemotherapy (n=10), chemoimmunotherapy (n=16), immunotherapy (n=13), or initial resection without subsequent systemic treatment (n=16). Forty five (82

Neoadjuvant therapy (NAT) is recommended for locally advanced gastric cancer (LAGC), but some patients respond poorly. We aimed to construct a multimodal model integrating CT images, transcriptomic sequencing, and clinicopathological data to assess prognosis in LAGC patients receiving NAT. This multicenter study included 505 LAGC patients who underwent NAT. Radiomic features were extracted from preoperative CT images of 505 patients. RNA-seq was performed on 277 post-NAT specimens, with additional data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (n = 804). Patients were divided into training (168 cases), internal validation (72 cases), and external validation cohorts. Machine learning algorithms identified key radiomic, molecular, and clinical features associated with NAT response, which were then integrated into a multimodal model to predict overall survival (OS) and disease-free survival (DFS). Six radiomic and three molecular features significantly associated with NAT response were selected. Radiomic risk (hazard ratio [HR]: 4.0, P < 0.001) and molecular risk (HR: 7.1, P < 0.001) were independent prognostic factors. By integrating radiomic risk, molecular risk, and clinical characteristics, a multimodal model (MuMo) was constructed.The C-index results (OS, C-index = 0.855; DFS, C-index = 0.786) demonstrated that MuMo outperformed the single-modality models and ypTNM staging.Mechanistic analysis suggested that the efficacy of neoadjuvant therapy was significantly enriched in immune-inflammatory pathways. MuMo can effectively predict postoperative survival risk in LAGC patients receiving NAT, serving as a powerful tool for optimizing prognostic assessment.

The standard treatment for stage IV gastric cancer (GC) is chemotherapy, but advances in systemic therapy have rendered curative surgery a viable option. However, the role of minimally invasive surgery (MIS) in this context remains unclear. This multicenter retrospective cohort study aimed to evaluate safety and effectiveness of MIS post-chemotherapy for patients with cStage IVb GC. Patients with cStage IVb GC who underwent curative-intent MIS or open surgery post-chemotherapy at 19 institutions between 2011 and 2022 were reviewed. Propensity score-matching was performed to adjust for confounding variables. The primary outcome was postoperative complications. Secondary outcomes were perioperative outcomes and long-term survival. Among 237 eligible patients (MIS, 130; open surgery, 107), 64 matched pairs were analysed. The incidence of Clavien–Dindo grade ≥ II complications was 31.2

EMILIN-1 is an extracellular matrix glycoprotein with tumor-suppressive functions. While its loss is implicated in cancer progression, its specific role in the gastric tumor microenvironment and its clinical relevance remain poorly defined. Using in vitro cellular systems and genetically modified mouse models we investigated the consequences of impaired EMILIN-1 function on gastric epithelial transformation, stromal remodeling, and fibroblast reprogramming. Histopathological analysis, gene expression profiling, and functional assays were employed to assess phenotypic changes in epithelial, fibroblastic, and endothelial compartments. We found that gastric cancer (GC) cells downregulate EMILIN-1 in stromal fibroblasts and lymphatic endothelial cells via paracrine signaling, leading to reduced EMILIN-1 deposition and disrupted lymphatic organization. Mechanistically, the interaction between EMILIN-1 and α4β1 integrin, which is absent in GC cells, modulates tumor cell proliferation; loss of this axis allows tumor cells to escape ECM-mediated growth control. Furthermore, EMILIN-1 downregulation reprograms fibroblasts into a pro-tumorigenic phenotype, which enhances GC cell migration and clonogenic potential. EMILIN-1 loss-of-function (E955A) mice showed increased susceptibility to pre-neoplastic lesions, a finding mirrored in human dysplastic tissues where EMILIN-1 was markedly reduced. Our findings establish EMILIN-1 as a master regulator of gastric tissue integrity. Its loss creates a tumor-permissive microenvironment by disrupting epithelial homeostasis, impairing lymphatic structure, and promoting fibroblast activation. The consistent reduction of EMILIN-1 in early human dysplasia highlights its potential as a novel stromal biomarker for early GC risk stratification. Moreover, restoring the EMILIN-1/integrin axis represents a promising therapeutic strategy to re-establish growth control and suppress tumor progression.

Serum trefoil factor 3 (TFF3) has emerged as a promising biomarker for gastric cancer; however, its biological origin remains unclear. Gastric cancer was induced by Helicobacter pylori infection combined with N-methyl-N-nitrosourea (MNU), whereas a rat model was established using N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) alone. Serum TFF levels were measured by ELISA. Organ-specific TFF3 expression, cytokine profiles, STAT3 activation, and epigenetic regulation were analyzed using RT-PCR, immunohistochemistry, multiplex assays, Western blotting, and ChIP–qPCR. Serum TFF1–3 levels were significantly elevated in gastric cancer–bearing mice, with TFF3 showing robust diagnostic performance. In rats, serum TFF3 levels remained unchanged after total gastrectomy. TFF3 expression was selectively upregulated in the liver, accompanied by STAT3 activation. Gastric IL-6 expression was increased, suggesting portal-mediated signaling to the liver. ChIP–qPCR demonstrated sustained enrichment of H3K27ac at the TFF3 locus following IL-6 stimulation. Increased serum TFF3 in gastric cancer originates from the liver and is associated with IL-6–STAT3 signaling. Persistent elevation after gastrectomy may be explained by epigenetic activation, supporting the biological basis of TFF3 as a surrogate marker.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor arising from the gastrointestinal tract. Accurate pathological diagnosis and appropriate treatment for this malignancy require a multidisciplinary approach. In consideration of the differences in clinical practice between Asian and Western countries, the Asian Consensus Guidelines for the Diagnosis and Management of GISTs were published in 2016 by multidisciplinary experts in Asian countries (Japan, Korea, China, and Taiwan). Given the accumulation of new evidence since the previous publication, a multidisciplinary expert panel consisting of pathologists, surgical oncologists, and medical oncologists revised the Asian consensus guidelines. This narrative review provides updated consensus recommendations reflecting available evidence, expert opinion, and current clinical practice for the diagnosis and management of GIST in Asian countries.

Gastric cancer is the fifth most commonly diagnosed cancer. Although 10

Papillary adenocarcinoma (Pap) is a relatively rare histological subtype of differentiated adenocarcinoma, and its biological behavior has not been fully elucidated. The present study aimed to clarify the clinicopathological characteristics of Pap. This study retrospectively included 1701 patients with differentiated-type gastric cancer who underwent gastrectomy at our institution between 2009 and 2021. Clinicopathological characteristics, recurrence patterns, and survival outcomes were compared between the two groups. Patients in the Pap group were older and showed higher rates of venous—and lymphatic invasion, as well as more advanced clinical and pathological stages. In the multivariate analysis of cumulative recurrence, histological type was identified as an independent predictor (HR 2.051, p = 0.037). The most common initial site of recurrence was the liver in both groups, with a significantly higher incidence observed in the Pap group (p < 0.001). In the multivariate analysis of overall survival, histological type was also identified as an independent prognostic factor (HR 1.962, p = 0.044). Pap showed poorer survival than the Tub group, with a particularly higher incidence of liver metastasis recurrence.

Immunotherapy offers promise for gastric cancer (GC) patients, yet its efficacy is substantially limited by high rates of treatment resistance, the mechanisms of which remain incompletely characterised. We aimed to delineate the role and mechanistic basis of CXCL12 in conferring anti-PD-1 resistance in GC. An anti-PD-1-resistant GC mouse model was established through chronic anti-PD-1 induction and in vivo tumour tissue passaging. Human and murine GC cell lines stably overexpressing CXCL12 (OE-CXCL12) were generated via lentiviral transduction to construct corresponding OE-CXCL12 GC mouse models. Single-cell transcriptomics analysed the tumour microenvironment (TME) in anti-PD-1-resistant GC. Molecular docking and Drug Affinity Responsive Target Stability (DARTS) assays predicted and validated ligand-receptor binding, respectively. RNA or protein expression of specific molecules was quantified by RT-qPCR, ELISA, immunofluorescence, and western blotting. Anti-PD-1-resistant GC models showed upregulated CXCL12, PD-L1, and CD206 expression with unchanged PD-1. OE-CXCL12 reduced anti-PD-1 sensitivity, elevated M2-TAM infiltration and TGF-β, IL-10, IL-4 levels in TME, reduced M1-TAM and CD8⁺ T cell infiltration and IL-12 level, with differentially expressed genes enriched in HIF-1, PD-L1/PD-1 checkpoint, and PI3K/AKT signalling pathways. M2-TAM-conditioned medium elevated SOX2, OCT-4, NANOG in GC cells. Mechanistically, CXCL12 binds CXCR4 to activate PI3K/AKT/HIF-1α, promoting PD-L1 expression and M2-TAM polarisation. CXCL12 inhibition recovered anti-PD-1 efficacy. This identifies CXCL12 as a novel anti-PD-1 resistance gene in GC, with the CXCL12/CXCR4/PI3K/AKT/HIF-1α axis induces anti-PD-1 tolerance through a dual-pathway mechanism of promoting PD-L1 expression and M2-TAM polarisation, providing potential therapeutic strategies to prevent and reverse anti-PD-1 resistance in GC.

Peritoneal metastasis (PM) is the most common and clinically devastating mode of spread in Gastric Cancer. Despite advances in systemic therapy, outcomes for gastric cancer with peritoneal metastasis (GCPM) remain poor, largely because the distinctive biology of PM, including sparse vascularization and the peritoneal–plasma barrier, restricts drug delivery and promotes therapeutic resistance. To overcome these limitations, locoregional approaches such as cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced, but their broader use remains limited by invasiveness, patient selection challenges, and variable survival benefits. In this setting, catheter-based normothermic intraperitoneal chemotherapy (CBIP) has emerged as a practical and scalable strategy, particularly in East Asia. By enabling repeated intraperitoneal administration through an implanted port, CBIP provides sustained regional drug exposure with minimal procedural burden and can be readily combined with systemic therapy. Among available agents, Paclitaxel and Docetaxel are especially suitable because of their prolonged peritoneal retention and low systemic absorption. Accordingly, taxane-based CBIP represents a biologically rational and clinically feasible platform for GCPM. In this review, we summarize its pharmacologic basis, clinical evidence, and future innovations in drug formulation and delivery that may further improve outcomes in this highly challenging disease.

Patients who undergo total gastrectomy lose the ability to produce intrinsic factor and require lifelong supplementation to prevent vitamin B12 deficiency. While oral B12 has emerged as a potential alternative to parenteral therapy, data remain limited, and most clinicians still favor intramuscular injections. This scoping review aimed to map the current evidence on the efficacy, safety, and implementation of oral vitamin B12 supplementation in patients after total gastrectomy for gastric cancer. We included peer-reviewed studies reporting outcomes of oral vitamin B12 supplementation after total gastrectomy. A systematic literature search was conducted in scientific databases, including articles published up to November 2025. The reference lists of included articles were screened manually. Extracted data were synthesized narratively. The review was conducted in accordance with the PRISMA-ScR guidelines. Seven studies (n = 449, including 310 patients receiving oral B₁₂) were included. Most used mecobalamin at daily doses of 500–1500 µg. Oral B12 consistently normalized serum levels and alleviated symptoms in the majority of patients. Comparative studies showed that, in terms of biochemical response, oral supplementation was not inferior to parenteral therapy. However, symptom monitoring was inconsistent, follow-up durations were generally short (< 6 months), and only one study was randomized. Standardized clinical outcome measures were rarely used, and data from Western populations were limited. Heterogeneity in dosing regimens and B12 formulations further limited comparability across studies. Oral B12 appears to be a feasible route of supplementation after total gastrectomy, but current evidence is limited by heterogeneity, underreporting of clinical outcomes, and lack of long-term follow-up. High-quality trials with standardized outcome measures are warranted.

Artificial intelligence (AI) has rapidly advanced in surgical applications. However, existing single-modality AI models relying solely on image input lack the ability to integrate anatomical understanding with clinical reasoning, which is essential for safe and actual surgical decision-making. We constructed an AI model with multimodal training combining visual and linguistic data and named Surgical Vision-Language Model (Surgical-VLM) for real-time surgical support. We analyzed surgical videos from 50 cases of robotic distal gastrectomy and extracted 50 still images per case, generating 10,000 vision–question–answer (VQA) pairs. The model was fine-tuned using the Large Language and Vision Assistant (LLaVA) framework. Model performance was assessed using the newly developed Surgical-VLM Bench, which evaluates appropriateness of expression, anatomical accuracy, and clinical usefulness on a 5-point scale, and the Bidirectional Encoder Representations from Transformers (BERT) score. The results were compared with those of ChatGPT-5. Surgical-VLM achieved a mean total benchmark score of 11.33 ± 0.697 versus 10.72 ± 0.536 for ChatGPT-5. Surgical-VLM showed numerically higher mean scores in anatomical accuracy and clinical usefulness. The BERTScore was 0.768 ± 0.008 for Surgical-VLM and 0.804 ± 0.013 for ChatGPT-5. This proof-of-concept study demonstrates the feasibility of domain adaptation for a Surgical-VLM and proposes a clinically grounded benchmark for structured evaluation. In this pilot setting, the prototype generated context-aware responses and showed domain-dependent differences compared with a general-purpose multimodal model. Further validation with larger independent test sets, expanded VQA items, and external evaluators is required before any clinical use.

While the incidence of early-stage remnant gastric cancer (RGC) is increasing, evidence for the validity of endoscopic resection (ER) for RGC remains limited. We aimed to clarify outcomes of ER for RGC. This is the second analysis of a nationwide prospective cohort study of ER for early gastric cancer (EGC) at 41 Japanese centers from July 2010 to June 2012. We compared short-term and long-term outcomes of 355 patients with 369 RGCs and 8460 patients with 9394 primary EGCs in the naïve stomach. We calculated 5-year overall survival (OS) and disease-specific survival (DSS) rates. Hazard ratios (HRs) for all-cause mortality were estimated using a Cox regression model; patients with curatively resected primary EGC were the reference group. For RGCs and primary EGCs, median procedure times were 87 and 77 min (p < 0.001); en-bloc resection rates were 96.7 and 99.5