Search Results (3,809)

Helicobacter pylori infection is a major cause of gastric cancer, and eradication before advanced precancerous gastric changes develop provides a biologically plausible opportunity for primary prevention. Adolescence represents a strategically favorable, although not universally established, window for intervention in Japan because persistent childhood-acquired infection can be identified before extensive mucosal damage while school-based programs provide organized access to defined birth cohorts. This narrative review evaluates the evidence supporting population-based adolescent H. pylori screening, its potential harms and uncertainties, and the lessons derived from Japanese implementation. Representative programs demonstrate that organized screening is feasible but show substantial heterogeneity in participation, diagnostic pathways, antimicrobial resistance, eradication outcomes, and retention across the care cascade. Direct evidence that adolescent screening reduces future gastric cancer incidence or mortality is not yet available. As H. pylori prevalence declines, the balance among screening yield, diagnostic performance, antimicrobial exposure, cost, and equity will continue to change. International experience further indicates that prevention strategies should be matched to local epidemiology and healthcare systems. Adolescent screening should therefore be viewed as an adaptive prevention strategy whose target population, diagnostic pathway, and treatment approach require periodic reassessment. Full article

Background/Objectives: H. pylori is the main preventable risk factor for gastric cancer through the development of extensive precancerous lesions, namely mucosal atrophy and intestinal metaplasia. Methods: This multicenter, nationwide study enrolled consecutive patients who underwent their first upper gastrointestinal endoscopy with standard biopsies. Clinical, endoscopic and histological data were gathered for statistical analysis using both univariate and multivariate analyses. Results: Data from 775 patients were collected, and H. pylori infection was detected in 172 (22.2%) cases. The infection prevalence significantly increased with age, and it was significantly higher in patients aged ≥50 years compared to younger patients (26.2% vs. 13.7%; p < 0.001; OR: 2.23; 95% CI = 1.48–3.36). The prevalence of extensive gastric precancerous lesions was 2.6%. The multivariate analysis showed that H. pylori infection (OR: 4.77; 95% CI = 1.51–15; p = 0.007), family history of gastric cancer (OR: 4.86; 95% CI = 1.36–15; p = 0.007), and age (OR: 1.07; 95% CI = 1.02–1.13; p = 0.007) independently increased the risk of these lesions. Conclusions: Data provided by this large study on the endoscopic prevalence of both H. pylori infection and extensive precancerous lesions in the stomach may be useful for designing preventive strategies aimed at reducing gastric cancer mortality. Full article

Background: Anastomotic leak (AL) is a major complication after esophagectomy, and gastric conduit perfusion is considered a key determinant of anastomotic integrity. Indocyanine green (ICG) fluorescence angiography is increasingly used for intraoperative perfusion assessment, although its clinical effect remains uncertain. We evaluated whether routine implementation of ICG assessment was associated with a lower incidence of AL compared with a historical no-ICG cohort, and explored intraoperative factors potentially associated with AL. Methods: Single-center before–after cohort study of consecutive adults undergoing Ivor-Lewis esophagectomy for cancer between January 2023 and December 2025, using a prospectively maintained database. ICG entered routine practice in March 2025, defining a historical no-ICG cohort and an ICG cohort. ICG (2 mL of a 25 mg/10 mL solution) was administered at three intraoperative timepoints; time to fluorescence (TTF), arcade–conduit fluorescence pattern, arterial blood gas values, and hemodynamic parameters were recorded. AL was defined according to Esophagectomy Complications Consensus Group criteria. Results: Sixty patients were included (ICG, n = 17; no-ICG, n = 43). AL occurred in 4/17 (23.5%) versus 5/43 (11.6%) patients (odds ratio 2.34, 95% CI 0.54–10.05; p = 0.256). Overall postoperative morbidity, conduit necrosis, pulmonary and infectious complications, reintubation, and 90-day mortality did not differ; a single death occurred, in the no-ICG cohort. All TTF values were below 60 s (range 23–46 s) and did not differ between patients with and without AL, nor did the fluorescence pattern; ICG never modified the planned anastomotic site or prompted additional conduit resection. Exploratory within-ICG analyses showed lower thoracic-phase PaO₂ and PaCO₂ and higher pH in patients who developed AL. Conclusions: Routine qualitative ICG assessment of gastric conduit perfusion was feasible; however, this small before–after cohort was insufficient to determine its effect on AL. Larger studies using standardized quantitative fluorescence assessment are required. Full article

Rnd3 is an atypical member of the Rho GTPase family whose activity is mainly regulated by expression, localization and protein stability rather than canonical GDP/GTP cycling. In cancer, Rnd3 has been described both as a tumor suppressor and as a tumor-promoting factor, creating an apparent functional paradox. We propose that this paradox is resolved by a mechanistic invariant: Rnd3 exerts a conserved inhibition of RhoA/ROCK1-dependent actomyosin contractility, whose phenotypic output is redirected by context-specific accessory effectors rather than reversed. In this review, we revisit this paradox by integrating evidence from mechanistic studies, tumor models and patient-associated datasets. We propose that Rnd3 should not be interpreted through a binary oncogene/tumor-suppressor framework, but rather as a context-dependent regulator of tumor cell state. In many tumor settings, Rnd3 repression or loss of Rnd3 function favors proliferation, apoptosis resistance and therapy resistance through pathways involving Notch, NF-κB, EGFR/ERK, EZH2-dependent chromatin regulation, m6A-mediated RNA control, microRNAs and chaperone-mediated autophagy. However, in selected contexts, including RTK-driven glioblastoma, hepatocellular carcinoma, non-small-cell lung cancer, melanoma and gastric cancer, Rnd3 may support tumor fitness, migration or invasive plasticity. We therefore propose a functional stratification model in which Rnd3 output depends on the biological process, tumor lineage, pathway activity and mechanical state of the cell. Full article

Background/Objectives: Days alive and out of the hospital at 30 days (DAOH30) integrates survival, index hospitalization, and readmission. We characterized DAOH30 after gastrectomy, assessed its complication-severity gradient and readmission burden, and explored its association with an index-cancer-excluded Charlson Comorbidity Index (CCI). Methods: This single-center retrospective analysis included adults undergoing R0 total gastrectomy or subtotal distal gastrectomy for non-metastatic gastric adenocarcinoma between January 2020 and April 2026. DAOH30 was derived from the index postoperative length of stay, readmission days, and 30-day mortality. Rank-based tests and median quantile regression were used. Results: Among 123 patients, median DAOH30 was 21 days (interquartile range, 18–22; range, 4–26). No 30-day deaths occurred; eight patients (6.5%) were readmitted. Median DAOH30 decreased from 22 days without complications to 21 days after Clavien–Dindo grade I–II complications and 17 days after grade ≥ III complications (Kruskal–Wallis p < 0.001; one-sided Jonckheere–Terpstra p < 0.001; two-sided permutation sensitivity p < 0.001). After adjustment, grade ≥ III complications were associated with 4.00 fewer median DAOH30 days (bootstrap 95% confidence interval, −7.31 to −2.25; model-based p < 0.001). Readmissions contributed 73 additional inpatient days, with a median decrement of 9.5 days per readmitted patient. No statistically significant independent association was detected between the index-cancer-excluded CCI and DAOH30 (adjusted median difference, −0.17 days per point; bootstrap 95% confidence interval, −1.34 to 0.40; model-based p = 0.640). Conclusions: DAOH30 summarized early hospital burden, but in this no-mortality, low-readmission cohort it was largely determined by index length of stay. Multicenter validation with patient-reported anchoring is warranted. Full article

Background and Objectives: Intra-corporeal esophagojejunostomy after totally laparoscopic total gastrectomy (TLTG) remains one of the most technically demanding steps of minimally invasive gastric surgery. The management of the common entry hole in linear stapler-based reconstructions still relies on advanced intra-corporeal suturing. The sutureless L-shape esophagojejunostomy with endoscopic assistance (SLEJ) technique, previously described by our group, was developed to overcome this limitation by combining an L-shaped linear stapler configuration with intraoperative endoscopic quality control. Building upon our initial results on the perioperative feasibility of the technique, the present study aimed to evaluate its intermediate-term anastomotic, functional, and oncological outcomes. Materials and Methods: Patients who underwent TLTG with D2 lymph node dissection and SLEJ reconstruction for gastric cancer between July 2024 and January 2026 were evaluated. Eligibility criteria included a minimum postoperative follow-up of six months, clinical and endoscopic surveillance, and complete contrast-enhanced thoraco-abdominopelvic computed tomography records. Protocol-based upper gastrointestinal endoscopy was performed at six-month intervals irrespective of symptoms to objectively assess anastomotic lumen width, mucosal healing, reflux findings, and possible intraluminal recurrence. The primary endpoint was anastomosis complication-free survival (anastomotic stenosis, alkaline reflux/reflux esophagitis, marginal ulcer, bleeding due to ulceration, and intraluminal recurrence); secondary endpoints were disease-free survival (DFS), local recurrence and changes to nutritional status. Results: A total of 26 patients (18 men and 8 women; mean age 59.0 ± 7.8 years) were analyzed. Anastomotic stricture developed in two patients and was successfully managed with two sessions of endoscopic balloon dilation in both. Similarly, alkaline reflux was documented in two additional patients and resolved under medical treatment. None of the patients required surgical revision. The mean ACFS follow-up duration was 12.42 months with ACFS rates of 92.3% at six months and 81.1% from the twelfth month onward. No local anastomotic recurrence was detected during follow-up. Disease progression occurred in four patients (15.4%), presenting as distant organ metastasis (n = 2) or peritoneal carcinomatosis (n = 2). The mean DFS follow-up duration was 12.62 ± 6.18 months, and the twelve-month OS and DFS rates were 82.1% and 84.0%. Postoperative body weight decreased significantly compared with preoperative values (76.69 ± 15.59 kg vs. 63.23 ± 10.55 kg; p < 0.001). A significant decrease was observed in the mean SMI between the preoperative and follow-up assessments (p < 0.001). The mean preoperative SMI was 49.90 ± 9.04 cm²/m², compared with 44.53 ± 7.98 cm²/m² at follow-up. No statistically significant changes were observed between the preoperative and follow-up periods for serum albumin and PNI variables (p = 0.703 and p = 0.970). Conclusions: The present intermediate-term analysis suggests that the SLEJ technique is feasible and associated with acceptable intermediate-term anastomotic, functional, and oncological outcomes in this preliminary single-center cohort. By standardizing common entry-hole management without intra-corporeal suturing and incorporating intraoperative endoscopic quality control, the technique offers a feasible alternative to established linear stapler-based reconstructions. Full article

Objectives: The present study investigated whether the pre-treatment Advanced Lung Cancer Inflammation Index (ALI) could serve as a prognostic indicator of disease-free survival (DFS) in patients with locally advanced gastric cancer treated with neoadjuvant chemotherapy followed by curative D2 gastrectomy. Methods: We retrospectively analyzed 157 patients with gastric adenocarcinoma who received treatment between 2016 and 2025. The pre-treatment ALI was derived from body mass index, serum albumin concentration, and the neutrophil-to-lymphocyte ratio. The association of clinical and laboratory variables with DFS was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression. Results: Median patient age was 63.6 years (61.1% male). Overall, 50.3% of patients experienced recurrence. Multivariate analysis demonstrated that ALI is an independent prognostic factor for DFS (HR = 0.867; 95% CI: 0.768–0.978; p = 0.020). Advanced age (p = 0.040), advanced clinical N stage (p < 0.001), and non-FLOT regimens (p = 0.003) also significantly predicted poorer DFS. Kaplan–Meier analysis confirmed that median DFS was significantly shorter in the low ALI group (38.9 months) compared to the high ALI group (52.0 months; p = 0.029). Conclusions: A low pre-treatment ALI score independently predicts shorter DFS in locally advanced gastric cancer patients treated with neoadjuvant chemotherapy and surgery. ALI serves as an accessible, low-cost biomarker to identify high-risk patients, warranting further prospective validation. Full article

Background: Nutritional deterioration is a common consequence of gastrectomy for gastric cancer and may persist despite standardized perioperative care. However, prospective longitudinal evidence describing the early course of postoperative nutritional recovery remains limited. This study aimed to characterize nutritional recovery trajectories following curative gastrectomy and to evaluate the influence of the extent of gastric resection on postoperative recovery. Methods: A prospective cohort of 239 consecutive patients undergoing curative-intent subtotal or total gastrectomy for gastric adenocarcinoma was followed between January 2022 and December 2025. The longitudinal complete-case analysis included 217 patients with available assessments at all three predefined time points: preoperatively (T0), at hospital discharge (T1), and three months after surgery (T3). Nutritional–immune biomarker trajectories were assessed preoperatively (T0), at hospital discharge (T1), and three months after surgery (T3) using serum albumin, total cholesterol, absolute lymphocyte count, and the Controlling Nutritional Status (CONUT) score. Longitudinal changes were evaluated using linear mixed-effects models with patient-specific random intercepts. Results: All evaluated nutritional–immune biomarkers changed significantly in an adverse direction after surgery, reaching their most unfavorable values at hospital discharge (all p < 0.001), followed by partial biochemical recovery at three months. Because albumin, lymphocyte count, and CONUT are influenced by the acute inflammatory and metabolic response to surgery, the discharge changes should not be interpreted as direct evidence of acute malnutrition. Nevertheless, none of the evaluated biomarkers returned to its preoperative value. Recovery between discharge and three months represented 65.6% of the initial decline for serum albumin, 50.5% for absolute lymphocyte count, 51.7% for total cholesterol, and 60.9% for the CONUT score. After adjustment for age, sex, neoadjuvant chemotherapy, baseline body mass index, ASA status, pathological T3–T4 stage, and major postoperative morbidity, total gastrectomy was associated with a greater early decline in absolute lymphocyte count at hospital discharge (β = −165.7 cells/mm³; 95% CI, −204.9 to −126.6; p < 0.001). This difference was no longer present at three months (p = 0.955). No significant time-by-gastrectomy interactions were observed for albumin, cholesterol, or corrected CONUT. Conclusions: Nutritional recovery following gastrectomy is a dynamic and prolonged process characterized by marked early nutritional–inflammatory biomarker changes and incomplete biochemical restoration at three months. Resection extent was not independently associated with persistently less favorable albumin, cholesterol, or corrected CONUT trajectories. The findings describe early biochemical changes and should not be extrapolated to body composition, functional recovery, micronutrient status, quality of life, or long-term survivorship. These findings apply primarily to patients who survived and completed the three-month follow-up. Full article

Background/Objectives: Gastric cancer remains a leading cause of cancer-related mortality worldwide, highlighting the need for novel therapeutic strategies. Drug repositioning offers a cost-effective approach by identifying new therapeutic applications for clinically approved drugs. Fluphenazine (FPZ), a dopamine receptor D2 antagonist used as an antipsychotic drug, has demonstrated anticancer activity; however, its effects on gastric cancer remain unclear. Methods: This study investigated the anticancer effects of FPZ alone and in combination with cisplatin (DDP) in gastric cancer. Results: In MKN-45 cells, viability was 100%, 101.16%, 61.26%, and 53.12% in the control, FPZ, DDP, and combination groups, respectively; the corresponding values in AGS cells were 100%, 84.95%, 89.94%, and 73.94%. FPZ also inhibited migration and induced apoptosis, while combined treatment increased cytosolic and mitochondrial reactive oxygen species levels and mitochondrial stress. Furthermore, FPZ reduced IL-6 and IL-8 expression and attenuated DDP-induced inflammatory responses. In the mouse xenograft model, the tumor volumes were 1233.65, 1115.75, 768.88, and 309.44 mm³ in the control, FPZ, DDP, and combination groups, respectively. Conclusions: These findings support the potential of FPZ as a repurposed anticancer agent for gastric cancer, particularly in combination with DDP. Full article

Background/Objectives: Gastric cancer (GC) remains a leading cause of cancer-related mortality, with metastasis being the primary driver of poor prognosis. The extracellular matrix glycoprotein tenascin-C (TNC) is implicated in tumor progression and metastasis, yet its regulatory mechanisms in GC remain poorly understood. Here, we identify RNA N6-methyladenosine (m6A) demethylase fat mass and obesity-associated protein (FTO) as a key modulator of TNC expression, promoting epithelial–mesenchymal transition (EMT) and GC metastasis. Methods: Integrating The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) and Gene Expression Omnibus (GEO) datasets (GSE246567, GSE181840, GSE163126, GSM4837878), we demonstrate that TNC is significantly upregulated in GC and correlates with worse clinical outcomes. Functional assays both in vitro and in vivo reveal that TNC knockdown suppresses GC cell proliferation, migration, invasion, and tumor metastasis, while overexpression of TNC rescues these effects. Mechanistically, FTO selectively demethylates TNC mRNA, reducing m6A modification at the 3’ untranslated region, thereby enhancing TNC mRNA stability and expression. RNA pull-down assays identify YTH domain family protein 2 (YTHDF2) as the m6A reader that recognizes the methylated site on TNC 3’UTR, and YTHDF2 knockdown partially rescues TNC expression and stability upon FTO loss. m6A RNA immunoprecipitation (MeRIP) and dual-luciferase reporter assays confirm FTO’s direct regulation of TNC via m6A demethylation. Furthermore, TNC promotes EMT by activating the phosphoinositide 3-kinase (PI3K)-AKT (protein kinase B) signaling pathway, as demonstrated by rescue experiments using the AKT activator SC79 and the PI3K inhibitor LY294002. Results: High FTO and TNC expression levels in clinical tissue samples correlate with poor patient survival. Conclusions: These findings reveal that the FTO/TNC/EMT axis represents a previously unrecognized epigenetic mechanism driving GC metastasis and suggest that targeting FTO-mediated m6A modification may provide a novel therapeutic strategy for GC patients with high metastatic potential. Full article

Background and Objectives: Tumor regression grade (TRG) in gastric cancer patients treated with neoadjuvant/perioperative chemotherapy is increasingly recognized as an important indicator of treatment efficacy and long-term prognosis. However, in geriatric patients, data on neoadjuvant therapy and on the relationship between pathological response and survival remain limited. In this study, we investigated the prognostic significance of pathological response, assessed according to Becker’s TRG in geriatric patients with locally advanced gastric adenocarcinoma who received neoadjuvant/perioperative chemotherapy and underwent gastrectomy. Materials and Methods: We retrospectively analyzed 82 patients aged ≥65 years with histologically confirmed gastric adenocarcinoma who received neoadjuvant/perioperative chemotherapy followed by curative gastrectomy at a single center between 2017 and 2024. Pathological response was evaluated using the Becker tumor regression grading (TRG) system and classified as good (TRG 1–2) or poor (TRG 3). Clinicopathological features, treatment characteristics, disease-free survival (DFS), and overall survival (OS) were compared between groups. Survival was estimated using the Kaplan–Meier method and compared with the log-rank test. Univariable and multivariable Cox proportional hazards models were used to assess the prognostic impact of TRG and other clinicopathological factors on DFS and OS. Results: The study included 82 geriatric patients, of whom 50 (61.0%) showed a good pathological response (TRG 1–2), while 32 (39.0%) showed a poor pathological response (TRG 3). Poor response was more frequently seen in clinical stage III disease and was accompanied by a higher rate of lymphovascular invasion. Median DFS was 42.4 months in the good response group versus 13.0 months in the poor response group (p < 0.001), and median OS was 47.7 and 15.5 months, respectively (p < 0.001). In multivariable analysis, ECOG performance status (HR 2.697; 95% CI 1.381–5.269; p = 0.004), lymphovascular invasion (HR 4.960; 95% CI 1.545–15.919; p = 0.007), and poor pathological response (HR 2.066; 95% CI 1.055–4.045; p = 0.034) remained independent predictors of DFS. For OS, ECOG performance status (HR 2.719; 95% CI 1.398–5.290; p = 0.003), lymphovascular invasion (HR 4.448; 95% CI 1.400–14.132; p = 0.011), and poor pathological response (HR 2.311; 95% CI 1.161–4.601; p = 0.017) remained independent predictors of OS. Conclusions: Our study suggests that pathological response assessed by the TRG system is a valuable prognostic marker in geriatric gastric adenocarcinoma. Good pathological response was associated with longer DFS and OS, while poor pathological response remained an independent predictor of both shorter DFS and OS. Full article

Background: Peritoneal metastasis (PM) is a lethal and often occult event in advanced gastric cancer (GC), and its preoperative detection remains difficult. The role of peripheral NK and NKT−like cells in predicting PM has not been well defined. Methods: We retrospectively analyzed 433 patients who underwent surgery for GC from 2016 to 2020. Patients were stratified by PM status and randomly assigned to training and held−out internal validation cohorts. Flow cytometry−derived lymphocyte subset percentages were treated as compositional data, and NK and NKT−like cell variables were entered into the model after log−ratio transformation. Candidate variables were selected using LASSO logistic regression in the training cohort and further assessed by multivariable logistic regression. Model performance was evaluated using AUROC, AUPRC, and confusion matrices in the validation cohort. Nomogram and SHAP analyses were used for model interpretation. Results: Seven predictors were retained in the final model: log−ratio−transformed NKT−like cells, direct bilirubin, prealbumin, lymphocyte count, lactate dehydrogenase, CA125, and log−ratio−transformed NK cells. The model achieved an AUROC of 0.879 (95% CI: 0.805–0.936) and an AUPRC of 0.698 (95% CI: 0.524–0.848) in the validation cohort. At the conventional threshold of 0.50, the model achieved an accuracy of 0.915, sensitivity of 0.821, specificity of 0.941, PPV of 0.793, and NPV of 0.950. At the Youden−optimal threshold of 0.101, sensitivity, specificity, accuracy, PPV, and NPV were 1.000, 0.892, 0.915, 0.718, and 1.000, respectively. Conclusions: A preoperative model integrating log−ratio−transformed NK/NKT−like cell variables and routine hematological parameters showed good ability to identify PM in GC and may help select patients for diagnostic laparoscopy or closer preoperative evaluation. Full article

Background/Objectives: Partially covered duodenal stents rapidly relieve malignant gastric outlet obstruction, but tumor overgrowth restenosis limits durability. We compared six preprocedural inflammatory, nutritional, and immune indices for predicting this outcome in patients with gastric cancer. Methods: We retrospectively analyzed 68 consecutive patients from a prospectively maintained cohort. The primary endpoint was endoscopically or radiologically confirmed tumor overgrowth restenosis. Discrimination was assessed using receiver operating characteristic curves (pairwise DeLong tests with Bonferroni correction) and time-dependent areas under the curve (AUCs) accounting for death as a competing risk. Multivariable cause-specific Cox models were restricted to preprocedural covariates; post-stenting chemotherapy or radiotherapy was examined in time-dependent sensitivity analyses. Results: Technical and clinical success rates were 100% and 94.1%. Seventeen patients (25.0%) developed restenosis at a median of 66 days. The C-reactive protein–albumin–lymphocyte (CALLY) index showed the highest AUC (0.859), followed by the C-reactive protein-to-albumin ratio (CAR; 0.822) and neutrophil-to-lymphocyte ratio (0.774); these three indices did not differ significantly. At an exploratory, internally derived cutoff of ≤0.110, CALLY had 76.5% sensitivity and 84.3% specificity and remained associated with restenosis after adjustment for stenosis site and stent length (adjusted hazard ratio, 12.30; 95% confidence interval, 3.89–38.83; C-index, 0.836), with consistent results in continuous, time-dependent, and tumor-covariate-adjusted analyses. The 180-day cumulative incidence was 52.4% with low CALLY versus 4.3% with high CALLY. Conclusions: C-reactive protein-based indices showed the highest numerical discrimination, although pairwise differences among CALLY, CAR, and NLR were not statistically significant. CALLY is a promising exploratory biomarker for restenosis risk stratification, but its cutoff should not guide clinical decisions until externally validated. Full article

Oral targeted therapies now constitute a substantial and growing proportion of anticancer drug therapy, shifting administration from the controlled intravenous setting to patient-managed oral therapy in the outpatient setting, where systemic exposure depends on factors that parenteral therapy largely bypasses. Food effects, gastric pH, first-pass metabolism, transporter activity, organ function, concomitant medications and adherence contribute to variability in exposure, and many oral anticancer agents have narrow therapeutic indices in which modest exposure changes carry clinical consequence. This review synthesizes the pharmacokinetic determinants of oral anticancer drug exposure across twenty-seven exemplar agents spanning the main mechanistic classes and translates them into actionable pharmacy practice. Its contribution is a cross-class agent-level comparison in which within-class divergences are made explicit, the integration of determinants usually reviewed separately, and an explicit statement of the evidence level behind every entry. We examine food effects, the interaction between acid-suppressive therapy and pH-dependent agents, the dominant role of cytochrome P450 3A4 and of the efflux transporters P-glycoprotein and breast cancer resistance protein, and the exposure–response relationships that motivate therapeutic drug monitoring, for which the evidence remains uneven and does not yet support routine use. We propose a structured framework for operationalizing these principles in daily practice. Full article

Gastric cancer remains a major cause of cancer mortality worldwide, mainly due to its frequent diagnosis at advanced stages and the high probability of recurrence even after curative treatment. Conventional postoperative follow-up is mainly based on imaging studies, endoscopy and serological tumor markers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 72-4 (CA72-4)This narrative review was based on a structured literature search of PubMed, Scopus, Web of Science, MEDLINE, the Cochrane Library, and ClinicalTrials.gov from database inception through June 2026, with 75 studies included in the final narrative synthesis. Among these analytes, circulating tumor DNA (ctDNA)currently provides the most mature data for the detection of molecular residual disease and postoperative risk stratification. Although it allows for the early detection of recurrent or residual disease prior to imaging confirmation, postoperative ctDNA has shown significant prognostic value in many studies; however, routine use as a basis for decision-making in treatment planning is still considered investigational and will require future prospective clinical validation. Tumor-informed ctDNA approaches offer high analytical specificity and sensitivity in low-burden disease settings. In contrast, tumor-agnostic approaches, such as methylation analysis and fragmentomics, may improve the scalability of the method. However, they require further validation in the postoperative setting. At the same time, emerging data indicate that extracellular vesicles, exosomal RNA and peritoneal lavage analytes can provide complementary biological information, especially in cases of peritoneal dissemination. Despite the significant prospects, the use of liquid biopsy in guiding the treatment of gastric cancer remains under investigation. This is because even today there are limitations. Characteristic are the low ctDNA excretion and the anatomical heterogeneity of the disease, as well as clonal hematopoiesis. Limitations also include the lack of standardization as well as the cost and the need for prospective clinical studies. This review summarizes the biological basis of molecular residual disease, liquid biopsy technologies, ctDNA data, the concept of molecular recurrence, and the future prospects of multi-analytic and artificial intelligence (AI)-assisted surveillance models in gastric cancer. Full article