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The present study aims to investigate whether malnutrition defined by the Global Leadership Initiative in Malnutrition (GLIM) criteria using hand-grip strength (HGS) adequately predict postoperative complications and long-term survival in patients underwent radical gastrectomy for gastric cancer in a similar manner to GLIM-defined malnutrition using skeletal muscle index (SMI).Patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019 were included in this study. Clinical data were prospectively collected. Malnutrition was diagnosed based on the two-step approach following the GLIM criteria. Skeletal muscle mass was assessed using SMI based on abdominal computed tomography (CT) scans, or assessed using HGS.A total of 1359 patients were included in this study, in which 36.2% of the patients were at risk of malnutrition (Nutritional Risk Screening 2002 scores ≥3). The incidence of malnutrition was 28.2% and 27.5% using SMI and HGS, respectively. There was a high agreement between the two criteria of malnutrition (kappa = 0.863, P 0.001). Both of the two criteria of malnutrition were independently associated with postoperative complications (SMI-GLIM, P = 0.041; HGS-GLIM, P = 0.023), overall survival (P 0.001, both), and disease-free survival (P 0.001, both), with similar odds ratio or hazard ratio after adjusting for the same confounding variables. HGS-GLIM malnutrition (P = 0.046) but not SMI-GLIM malnutrition (P = 0.270) was associated with a higher incidence of severe complications.GLIM criteria using HGS is a useful tool to diagnose malnutrition and has a similar or even better predictive value for postoperative complications and long-term survival after radical gastrectomy for gastric cancer compared with GLIM criteria using SMI.

ZIC2 is involved in the tumor progression of many types of cancers. The role of ZIC2 in the metastasis of colorectal cancer and its mechanism are not yet clear. In this study, we found that high ZIC2 expression was not only associated with poor prognosis, relapse-free survival and advanced metastasis but was also an independent prognostic factor in colorectal cancer patients. Moreover, ZIC2 knockdown inhibited cell proliferation, migration and invasion, while the upregulation of ZIC2 had the opposite effect in vitro. ZIC2 overexpression induced TGF-β1 expression and increased Smad3 phosphorylation. The carcinogenic effects of elevated ZIC2 expression can be eliminated by interfering with the TGF-β1 receptor with inhibitors. This further verified the promoting effect of ZIC2 on the TGF-β signaling pathway. In vivo experiments have also confirmed that ZIC2 can promote liver metastases of colorectal cancer. The results suggest that ZIC2 is associated with poor prognosis and relapse-free survival in colorectal cancer patients. Moreover, ZIC2 promoted colorectal cancer progression and metastasis by activating the TGF-β signaling pathway. Hence, ZIC2 is expected to be a new therapeutic and prognostic target for colorectal cancer in the future.

Summary Background The present study aims to investigate the prognostic value of Global Leadership Initiative in Malnutrition (GLIM)-defined malnutrition in overweight patients who underwent gastrectomy for gastric cancer, and to explore whether the addition of muscle quality, strength and gait speed could improve the predictive power for postoperative outcomes. Methods Overweight patients (body mass index (BMI) ≥23 kg/m2) who underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the two-step approach following the GLIM criteria. Skeletal muscle mass and quality was assessed using computed tomography (CT) determined skeletal muscle index (SMI) and skeletal muscle density (SMD), respectively. Hand-grip strength and 6-m gait speed were measured before surgery. Results A total of 587 overweight patients were included, in which 262 patients were identified as having obesity (BMI ≥25 kg/m2). The prevalence of malnutrition was 11.9% and 10.7% for overweight and obese patients, respectively. GLIM-defined malnutrition alone was not predictive for postoperative complications in overweight patients. The addition of low gait speed or muscle quality to GLIM-defined malnutrition led to a significant predictive value for postoperative complications. Low gait speed plus GLIM-defined malnutrition remained significant in the multivariate analysis. GLIM-defined malnutrition was predictive for overall survival (OS) and disease-free survival (DFS). Addition of low gait speed to GLIM-defined malnutrition increased the hazard ratio (HR) for the prediction of OS and DFS (univariate analysis: 2.880 vs. 2.238 for OS, 2.410 vs. 1.937 for DFS; multivariate analysis: 2.836 vs. 1.841 for OS, 2.433 vs. 1.634 for DFS). Addition of low hand-grip strength to GLIM-defined malnutrition led to a higher HR for the prediction of OS (2.144 vs. 1.841) in the multivariate analysis. Conclusion Muscle quality, strength and gait speed added prognostic value to GLIM-defined malnutrition for the prediction of postoperative complications and/or survival in overweight patients who underwent radical gastrectomy for gastric cancer, especially gait speed, which could be incorporated into nutritional assessment protocols.

Few studies have comprehensively analyzed the correlations among body composition parameters, muscle strength, and physical performance, as well as the influence of these factors on the postoperative complications and survival after radical gastrectomy for gastric cancer.A prospective study was conducted including patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral fat area (VFA), subcutaneous fat area (SFA) was obtained by measurement of preoperative computed tomography (CT) images. Grip strength and 6-m gait speed were measured to assess muscle strength and physical performance before surgery.There was a positive correlation between SMI and SMD, as well as between SFA and VFA. SMD negatively correlated with SFA and VFA. SMI had a positive correlation with VFA, but showed minimal correlation with SFA and visceral to subcutaneous fat ratio (VSR). Grip strength and gait speed were both positively correlated with SMI and SMD, but showed minimal correlation with SFA, VFA and VSR. SMI and grip strength independently predicted postoperative complications, rather than SMD or gait speed. Whereas SMD and gait speed had independent predictive value for overall survival (OS) and/or disease-free survival (DFS), rather than SMI or grip strength. VSR independently predicted postoperative complications, rather than VFA or SFA alone. Low SFA was an independent risk factor for OS and DFS. High VFA was associated with worse survival in overweight patients (body mass index, BMI ≥25), but was associated with better survival in non-overweight patients (BMI25). High SFA did not significantly influence survival in overweight patients, but was associated with better survival in non-overweight patients.There is an extensive and complex correlation among body composition parameters, grip strength, and gait speed in patients with operable gastric cancer. A comprehensive analysis of these parameters has significant predictive value for postoperative complications and survival.

Objectives We investigated whether measurement of muscle quantity/quality has additional predictive value for postoperative complications and long-term survival after gastrectomy for gastric cancer in patients with probable sarcopenia, as defined by the new European Working Group on Sarcopenia in Older People 2 consensus. Methods We conducted a prospective study of patients who underwent a radical gastrectomy for gastric cancer between August 2014 and June 2019. Muscle strength was measured using a handgrip dynamometer. Computed tomography images at the third lumbar vertebra level were used to assess muscle quantity and quality by the measuring cross-sectional muscle area and mean muscle attenuation, respectively. Probable sarcopenia was defined by low muscle strength. Sarcopenia was diagnosed by additional low muscle quantity or quality. Clinical outcomes were obtained by prospective data collection and follow up. Results Probable sarcopenia was identified in 419 patients, including 285 patients with sarcopenia. Patients with sarcopenia had a higher incidence of postoperative complications, higher costs, longer length of postoperative hospital stay, and worse overall survival (OS) and disease-free survival (DFS) compared with patients with low muscle strength only. The multivariate logistic analysis showed that sarcopenia and hypoproteinemia were independent risk factors for postoperative complications in patients with probable sarcopenia. Moreover, multivariate Cox analyses showed that sarcopenia remained an independent risk factor for OS and DFS in patients with probable sarcopenia. Conclusions The measurement of muscle quantity/quality has additional predictive value for postoperative complications, OS, and DFS after gastrectomy for gastric cancer in patients with probable sarcopenia.