Yogurt containing Lactobacillus paragasseri OLL2716 (LG21 yogurt) has been reported to improve delayed gastric emptying and modulate autonomic nervous system (ANS) activity. Ghrelin, a peptide hormone produced in the stomach, enhances gastric motility and acid secretion and modulates autonomic function. This study examined whether LG21 yogurt affects ghrelin-related responses in gastric cells. MKN45 cells, a human gastric adenocarcinoma-derived cell line, were treated with LG21 cells (live or heat-treated) or LG21 culture supernatant, and ghrelin messenger RNA (mRNA) expression was quantified. Both LG21 cells and the culture supernatant significantly increased ghrelin mRNA expression, suggesting contributions from bacterial cells and metabolites. To support the transcript data, secreted ghrelin was additionally measured by enzyme-linked immunosorbent assay after treatment with LG21 cells, and LG21 cells significantly increased ghrelin secretion. LG21 yogurt induced an earlier increase in ghrelin mRNA than did yogurt prepared with the starter strains Lactobacillus delbrueckii subsp. bulgaricus OLL1255 and Streptococcus thermophilus OLS3294 but without LG21 (LG21-free yogurt). The effect also varied by strain: LG21 increased ghrelin mRNA expression, whereas the L. paragasseri type strain showed no significant effect. Additional pharmacological experiments in MKN45 cells further supported the possibility that prostaglandin E2-EP4 signaling contributes to the ghrelin response in this model. These findings indicate that, in the exploratory in vitro MKN45 model used here, LG21 yogurt modulates ghrelin-related readouts in a strain-dependent manner, with contributions from both LG21 and the starter strains.

We present a case report of severe gastritis and colitis in the context of recent zolbetuximab administration in a patient receiving combination chemotherapy for metastatic gastric adenocarcinoma. This case highlights the potential gastrointestinal toxicity associated with zolbetuximab, particularly in patients with previous mucosal injury from chemotherapy and tumor involvement.

Liver metastasis is associated with reduced benefit from immune checkpoint inhibitors (ICIs) in several gastrointestinal cancers, yet the background liver status is rarely considered in immunotherapy biomarker studies. Here, we examine whether metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) may alter the immune environment of liver metastases and affect ICI efficacy. The available evidence is strongest, and most mechanistic, for colorectal liver metastasis and derives largely from preclinical models; it is emerging for pancreatic ductal adenocarcinoma and limited for gastric and biliary tract cancers. MASLD and MASH should not be treated as interchangeable: simple steatosis, active steatohepatitis, fibrosis, and cirrhosis represent distinct liver conditions with different possible effects on hepatic seeding and immune-cell access. Early steatohepatitic inflammation may promote hepatic colonization through lipid availability, hepatocyte stress, and myeloid-cell recruitment, whereas advanced fibrosis can reduce initial colonization while impairing lymphocyte access to established lesions. ICI efficacy requires viable tumor-reactive T cells, relief from myeloid-cell suppression, and direct tumor-T-cell contact; MASLD- and MASH-related liver changes may interfere with each of these requirements through mechanisms beyond checkpoint-ligand expression alone. We distinguish T-cell exhaustion from liver metastasis-associated T-cell deletion, and highlight macrophage-mediated elimination of tumor-specific CD8-positive T cells, myeloid chemokine signaling-driven suppressor-cell recruitment, and stromal remodeling as candidate mechanisms, supported mainly by preclinical evidence, that may reduce ICI response. These mechanisms remain unvalidated as predictors of ICI response in cohorts with MASLD/MASH staging. Future studies should assess liver fat, inflammatory activity, fibrosis stage, tumor genotype, and ICI outcomes in the same patients to test whether MASLD/MASH stage is associated with differential benefit.

Common variable immunodeficiency (CVID) is associated with immune dysregulation and an increased risk of gastric malignancy. The coexistence of CVID with autoimmune gastritis, pernicious anemia, and genetic defects such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency may suggest a possible association with altered gastric adenocarcinoma risk. However, the clinical interplay remains incompletely understood and not well established. We present a case of a 54-year-old Caucasian woman with a high-grade intestinal tubulovillous adenoma in the stomach body, who developed gastric adenocarcinoma, which was subsequently resected, and had a recurrence of the tumor with a background of chronic lymphocytic gastritis almost four years later. She was later diagnosed with CVID and was found to have pernicious anemia and CTLA-4 haploinsufficiency. This case highlights the potential interplay between CVID, CTLA-4 haploinsufficiency, and autoimmune gastric pathology in the development of gastric adenocarcinoma. Early recurrence despite initial curative resection underscores the need for increased vigilance and consideration of structured surveillance strategies in high-risk patients with overlapping autoimmune gastric conditions. Further research is needed to guide screening and prevention in this population.

Background/Objective: Laparoscopic gastrectomy (LG) and robotic gastrectomy (RG) exhibit similar surgical outcomes in patients with gastric cancer (GC), except for the higher cost associated with RG. Comparative surgical outcome studies after open conversion from laparoscopic (OL) and robotic (OR) gastrectomy in GC are limited. This study aimed to evaluate clinical effectiveness while considering differences in procedural cost. Methods: This retrospective cohort study included a comparative analysis of patients with GC who underwent OL or OR. Inclusion criteria were histologically confirmed adenocarcinoma and curative resection for GC using OL or OR. Exclusion criteria included initially planned open surgery and other laparoscopic or robotic procedures without gastrectomy. Clinicopathological characteristics, as well as short- and long-term surgical outcomes, were compared between groups. Results: Overall, 118 (1.9%) of 6336 LG cases and 10 (2.6%) of 384 RG cases were included (p = 0.3308). Clinicopathological characteristics were statistically comparable between groups. Postoperative complication incidence, evaluated using the Clavien-Dindo classification, was 19.5% and 10% in the OL and OR groups, respectively (p > 0.05). The median hospital stay was 8 and 9.5 days in the OL and OR groups, respectively (p > 0.05). Reasons for open conversion were similar between groups and included adhesion, bleeding, advanced disease, and positive resection margins, among others. Overall 5-year survival was 0.79 (0.72-0.88) and 0.88 (0.67-1.0) in OL and OR, respectively (p = 0.596). Conclusions: Short- and long-term surgical outcomes after OL and OR did not differ statistically. Selection of LG versus RG should be performed with caution.

Background/Objectives: Hepatoid adenocarcinoma is a rare adenocarcinoma subtype. Synchronous esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma with hepatoid differentiation is exceptionally uncommon. This report describes lesion-specific staging, pathological response assessment, and individualized management after neoadjuvant chemoimmunotherapy. Methods: De-identified clinical, imaging, laboratory, operative, and pathological data were retrospectively reviewed. Both lesions were staged according to the AJCC 8th edition and reassessed using the CAP modified Ryan four-tier tumor regression grading system. Results: A 61-year-old man presenting with dysphagia had separate ESCC and gastric cardia adenocarcinoma, both staged cT2N0M0. One cycle of pembrolizumab 200 mg, nab-paclitaxel 300 mg, and cisplatin 100 mg was administered. Agranulocytosis precluded further neoadjuvant therapy; after neutrophil recovery, R0 resection was performed. Pathological review showed ESCC ypT1aN0M0, score 1, and cardia adenocarcinoma ypT1aN0M0, score 3, with approximately 30% regional hepatoid differentiation. All 10 examined lymph nodes were negative. AFP was not measured before treatment; post-treatment/preoperative values were 14.45 and 14.68 ng/mL, and the postoperative value was 6.08 ng/mL. Postoperative tislelizumab monotherapy was selected as an individualized, non-standard strategy, mainly because of affordability. At approximately 6 months after surgery, no recurrence, metastasis, or maintenance-related adverse event was identified. Conclusions: This case emphasizes biopsy under-sampling and lesion-specific staging and pathological assessment. The regression-score difference is descriptive and confounded by baseline burden, histology, and one-cycle exposure; the AFP findings do not validate a surveillance biomarker.

Gastric cancer (GC) remains a major global health challenge, ranking among the most lethal malignancies due to late diagnosis, high tumor heterogeneity, and limited treatment efficacy. The search for safer, nutritionally based adjuncts to conventional therapies is therefore a research priority. Donkey milk (DM), traditionally used as a hypoallergenic substitute for infants, is emerging as a functional food with remarkable bioactivity. Its composition closely resembles human milk, with high levels of bioactive proteins, a favorable polyunsaturated lipid profile, antioxidant vitamins, and immune-supportive minerals. Despite its growing nutraceutical appeal, the anticancer potential of DM in GC has not yet been explored. This study represents the first investigation of DM in human gastric adenocarcinoma (AGS) cells. Using increasing concentrations of whole DM (25-100%), a dose-dependent inhibition of cell viability and migration was observed. Mechanistic insights reveal that DM induces mitochondrial oxidative stress, disrupts cell cycle progression (S/G2 accumulation at 75%, G2 arrest at 100%), and unexpectedly triggers a pro-inflammatory gene signature suggesting stress-driven immunostimulation rather than canonical apoptosis. These findings highlight a non-classical, context-dependent cytotoxic mechanism that distinguishes DM from conventional pro-apoptotic agents. DM may represent a promising nutraceutical candidate for GC management, bridging traditional food resources with modern oncology. By inhibiting hallmark cancer traits while engaging unique immunological pathways, DM offers a sustainable, low-toxicity approach with translational potential. Future studies will focus on the characterization of active components, validation in organoid and animal models, and exploring clinical applications of DM-derived bioactive components in cancer prevention and therapy.

Hydrophobic deep eutectic solvents (HDESs) have been recognized as effective environmentally friendly extraction media for the recovery of lipophilic bioactive chemicals. Nonetheless, their incorporation with sophisticated delivery systems remains mostly unexamined. This study aimed to develop a curcuminoid-rich powder formulation from turmeric (Curcuma longa L.) and to evaluate its physicochemical properties, antioxidant activity, and effects on cell metabolic activity in vitro. Initially, 30 HDES systems based on thymol or menthol were prepared and compared in terms of their curcuminoid extraction performance. The thymol/lactic acid system (2:1, molar ratio) produced the highest total curcuminoid concentration among the screened HDES systems. The extraction parameters were subsequently optimized using a Box-Behnken response surface design. Under the optimized conditions, the total curcuminoid concentration in the analyzed extract solution was 6692.12 ppm. Then, the obtained extracts were incorporated into a double-layer emulsification system by high-pressure homogenization and converted into encapsulated powder form by spray-drying. The particle distribution index (PDI) of the prepared emulsion system was determined as 0.282, indicating a homogeneous distribution of particles within the emulsion system. The total curcuminoid-based encapsulation efficiency of turmeric powders obtained using a double-layer encapsulation system was determined to be 87.33%. Under separately simulated gastric and intestinal conditions, the detected curcuminoid recovery values were similar, at 31.24% and 31.10%, respectively. The ABTS radical-scavenging activity measured after the simulated intestinal treatment reached 81.57%. However, the possible contribution of residual HDES components to this activity could not be determined. The encapsulated powder caused a concentration-dependent reduction in the metabolic activity of DU-145 prostate cancer and Caco-2 colorectal adenocarcinoma cells in the MTT assay. To conclude, the integrated approach enabled the production of a curcuminoid-rich powder with high encapsulation efficiency. The findings support further investigation of the formulation's technological and biological properties.