Malnutrition has been reported to lead to poor postoperative outcomes. The Global Leadership Initiative on Malnutrition (GLIM) criteria were published in 2019 as a global consensus on the criteria for diagnosing malnutrition. However, the relationship between GLIM-defined malnutrition and treatment outcomes in patients with cancer has not been fully investigated. Therefore, this study aimed to clarify the impact of GLIM-defined malnutrition on the treatment outcomes of patients with cancer. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov and identified observational studies published from inception to January 17, 2022. We conducted a systematic review and random-effects meta-analysis studies that included patients with cancer aged >18 years who received any kind of treatment and whose nutritional status was assessed using GLIM criteria. We independently assessed the risk of bias and quality of evidence using Quality In Prognosis Studies and Grading of Recommendations, Assessment, Development, and Evaluation approach. The primary outcomes were overall survival (OS) and postoperative complications. Hazard ratios and 95% confidence intervals (CIs) for OS and relative risk ratios and 95% CIs for postoperative complications were pooled. The protocol was published by PROSPERO (CRD42022304004). Of 67 studies after screening, ten studies (n = 11,700) reported the impact of GLIM-defined malnutrition on postoperative outcomes. Compared with no malnutrition, GLIM-defined malnutrition may worsen OS (hazard ratio, 1.56; 95% CI, 1.38-1.75; I² = 37%) and increase postoperative complications (relative risk ratio, 1.82; 95% CI, 1.28-2.60; I² = 87%). The risk of bias in each study was either moderate or high. The certainty of the evidence was low because of publication bias and a moderate or high risk of bias. GLIM-defined malnutrition may worsen OS and increase the risk of postoperative complications in patients with cancer undergoing treatment. Further studies are needed to confirm these findings and mitigate this risk.

There is no consensus on the efficacy of perioperative immunonutrition in patients with upper gastrointestinal (GI) cancer surgery. We clarified the impact of perioperative immunonutrition on postoperative outcomes in patients with upper GI cancers. We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981–2022 using search terms related to immunonutrition and upper GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy, including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were infectious complications, defined as events with a Clavien–Dindo classification grade ≥ II that occurred within 30 days after surgery. After screening, 23 studies were included in the qualitative synthesis and in the quantitative synthesis. The meta-analysis showed that immunonutrition reduced infectious complications (relative risk ratio: 0.72; 95% confidence interval: 0.57–0.92; certainty of evidence: Moderate) compared with standard nutritional therapy. In conclusion, nutritional intervention with perioperative immunonutrition in patients with upper GI cancers significantly reduced infectious complications. The effect of immunonutrition for upper GI cancers in reducing the risk of infectious complications was about 30%.

FOXO3 is a member of the FOXO transcription factors thought to play a tumor-suppressor role in gastrointestinal cancer, while tumor-promoting function of FOXO3 has also been reported. These results suggest a context-dependent function of FOXO3 in tumor development. However, the relationship between the FOXO3 expression pattern and its role in tumorigenesis has not been elucidated. We examined the FOXO3 expression in 65 human primary gastric cancer and patient-derived xenograft tissues by immunohistochemistry and identified three subtypes according to subcellular localization: FOXO3-nuclear accumulated (FOXO3-Nuc), FOXO3-nuclear/cytoplasmic or cytoplasmic distributed (FOXO3-Cyt), and FOXO3-negative. In the FOXO3-Cyt gastric cancer cells, the expression of the constitutive active mutant FOXO3 (Act-ER FOXO3) induced the nuclear accumulation of FOXO3 and significantly suppressed colony formation and proliferation. The inhibition of the PI3K-AKT pathway by inhibitor treatment also suppressed the proliferation of FOXO3-Cyt gastric cancer cells, which was associated with the nuclear accumulation of endogenous FOXO3. Furthermore, the expression of Act-ER FOXO3 by an endogenous promoter significantly suppressed gastric tumorigenesis in Gan mice, a model of gastric cancer. Finally, treatment of FOXO3-Cyt human gastric cancer-derived organoids with an AKT inhibitor significantly suppressed the survival and proliferation. These results indicate that FOXO3 is a latent tumor suppressor for FOXO3-Cyt-type gastric cancer cells and that activation of the PI3K-AKT pathway protects this type of gastric cancer cell from FOXO3-mediated growth suppression via constitutive nuclear export. Thus, the inhibition of the PI3K-AKT pathway and nuclear translocation of endogenous FOXO3 may have therapeutic applications in the treatment of FOXO3-positive and cytoplasmic-type gastric cancer.

This study investigated the paradox of high visceral fat mass increasing severe complications but improving long-term prognosis after radical gastrectomy for gastric cancer. This was a retrospective cohort study of consecutive patients with primary stage I–III gastric cancer who underwent gastrectomy between April 2008 and June 2018. The visceral adipose tissue index (VAI) was calculated by dividing the visceral fat mass preoperatively measured on computed tomography by the square of the height. Patients with VAIs below the median cut-off value were classified as low-VAI, while those above it were classified as high-VAI. We compared the postoperative complication rate and overall survival (OS) in the low- and high-VAI groups after adjusting patient characteristics using propensity score matching (PSM). There were 155 patients in both groups after PSM. After matching, there was no significant difference in factors other than BMI and VAI that were not adjusted. The high-VAI group had more severe postoperative complications (p = 0.018), but the OS was significantly better in the high-VAI group (hazard ratio 0.611, 95%CI 0.403–0.928, p = 0.021). Preoperative high visceral fat mass not only increased severe complications, but also improved OS after gastrectomy in patients with advanced gastric cancer.