Gastric cancer is one of the most frequent malignancies worldwide. Despite improvements in diagnosis and therapy, the overall prognosis remains poor. In the last decade, several anti-angiogenic drugs for cancer treatment have been approved and lately also introduced to gastric cancer treatment. While the initial trials focused only on unresectable or metastatic cancer, anti-angiogenic treatment is now also investigated in the perioperative and neoadjuvant setting. In this review, an overview of the role of angiogenesis and angiogenic factors in gastric cancer as well as anti-angiogenic treatment of gastric cancer is provided. Findings from in vitro and animal studies are summarized and put in a context with translational data on angiogenesis in gastric cancer. The most important angiogenic factors and their effect in gastric cancer are highlighted and clinical trials including anti-angiogenic drugs are discussed. Finally, an outlook of biomarkers for predicting response to anti-angiogenic treatment is presented, the ongoing trials on this topic are discussed and current challenges of anti-angiogenic therapy are outlined.

The enteric neurotransmitter acetylcholine governs important intestinal epithelial secretory and immune functions through its actions on epithelial muscarinic Gq-coupled receptors such as M3R. Its role in the regulation of intestinal stem cell function and differentiation, however, has not been clarified. Here, we find that nonselective muscarinic receptor antagonism in mice as well as epithelial-specific ablation of M3R induces a selective expansion of DCLK1-positive tuft cells, suggesting a model of feedback inhibition. Cholinergic blockade reduces Lgr5-positive intestinal stem cell tracing and cell number. In contrast, Prox1-positive endocrine cells appear as primary sensors of cholinergic blockade inducing the expansion of tuft cells, which adopt an enteroendocrine phenotype and contribute to increased mucosal levels of acetylcholine. This compensatory mechanism is lost with acute irradiation injury, resulting in a paucity of tuft cells and acetylcholine production. Thus, enteroendocrine tuft cells appear essential to maintain epithelial homeostasis following modifications of the cholinergic intestinal niche.

Various blood cell ratios exist which seem to have an impact on prognosis for resected gastric cancer patients. The aim of this systematic review was to investigate the prognostic role of blood cell ratios in patients with gastric cancer undergoing surgery in a curative attempt. A systematic literature search in MEDLINE (via PubMed), CENTRAL, and Web of Science was performed. Information on survival and cut-off values from all studies investigating any blood cell ratio in resected gastric cancer patients were extracted. Prognostic significance and optimal cut-off values were calculated by meta-analyses and a summary of the receiver operating characteristic. From 2831 articles, 65 studies investigated six different blood cell ratios (prognostic nutritional index (PNI), lymphocyte to monocyte ratio (LMR), systemic immune-inflammation index (SII), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR)). There was a significant association for the PNI and NLR with overall survival and disease-free survival and for LMR and NLR with 5-year survival. The used cut-off values had high heterogeneity. The available literature is flawed by the use of different cut-off values hampering evidence-based patient treatment and counselling. This article provides optimal cut-off values recommendations for future research.

Introduction: The incidence of early-onset gastric adenocarcinoma (patients 50years) in a surgical cohort and assess treatment options.

Objectives: The objective was to provide evidence for age-dependent use of neoadjuvant treatment by clinical comparisons of young (lower quartile, 71.3 years) patients with esophageal and esophagogastric-junction adenocarcinoma. Background: Neoadjuvant treatment is the standard of care for locally advanced and node-positive EAC. However, the effect of age on oncological outcomes is disputable as they are underrepresented in treatment defining randomized controlled trials. Methods: Patients with EAC undergoing esophagectomy between 2001 and 2022 were retrospectively analyzed from three centers. Patients having distant metastases or clinical UICC-stage I were excluded. Cox proportional hazards regression was used to identify the variables associated with survival benefit. Results: Neoadjuvant treatment was administered to 185/248 (74.2%) young and 151 out of 248 (60.9%) elderly patients (P=0.001). Young age was associated with a significant overall survival (OS) benefit (median OS: 85.6 vs. 29.9 months, hazard ratio 0.62, 95% CI: 0.42–0.92) after neoadjuvant treatment versus surgery alone. In contrast, elderly patients did only experience a survival benefit equaling the length of neoadjuvant treatment itself (median OS: neoadjuvant 32.8 vs. surgery alone 29.3 months, hazard ratio 0.89, 95% CI: 0.63–1.27). Despite the clear difference in median OS benefit, histopathological regression was similar ((Mandard-TRG-1/2: young 30.7 vs. old 36.4%, P= 0.286). More elderly patients had a dose reduction or termination of neoadjuvant treatment (12.4 vs. 40.4%, P<0.001). Conclusion: Old patients benefit less from neoadjuvant treatment compared to younger patients in terms of gain in OS. Since they also experience more side effects requiring dose reduction, upfront surgery should be considered as the primary treatment option in elderly patients.