Effects of different radical distal gastrectomy on postoperative inflammatory response and nutritional status in patients with gastric cancer.

Objectives: The inflammatory response caused by gastric cancer surgery and the low nutritional status of patients with gastric cancer can cause growth of tumour cells, reduce immunity, and increase tumour burden. We investigated the effects of different surgical methods on postoperative inflammatory response and nutritional status in patients with distal gastric cancer. Methods: Clinical data of 249 patients who underwent radical distal gastrectomy for distal gastric cancer from February 2014 to April 2017 were retrospectively analysed. Patients were divided according to the surgical method (open distal gastrectomy [ODG], laparoscopic-assisted distal gastrectomy [LADG] and total laparoscopic distal gastrectomy [TLDG]). Characteristics of different surgical procedures, including inflammation parameters and nutritional indicators, and different time points (preoperatively, 1 day postoperatively, and 1 week postoperatively) were compared using non-parametric test analysis. Results: At postoperative day 1, white blood cell count [WBC], neutrophil count [N], neutrophil/lymphocyte ratio [NLR], and platelet/lymphocyte ratio [PLR] increased in the three groups, and ΔN and ΔNLR were significant; the smallest change was observed in TLDG (P < 0.05). Albumin [A]and prognostic nutrition index [PNI] significantly decreased; the smallest ΔA and ΔPNI, which were statistically significant, were noted in TLDG. One week postoperatively, WBC, N, NLR, and PLR decreased, and WBC, N, and NLR showed significant difference. A and PNI of the three groups increased after 1 week, and A and PNI showed significant differences. Conclusion: Postoperative inflammatory response and nutritional status of patients with distal gastric cancer are associated with the surgical technique. TLDG has little influence on the inflammatory response and nutritional level compared with LADG and ODG.

Not All Kirsten Rat Sarcoma Viral Oncogene Homolog Mutations Predict Poor Survival in Patients With Unresectable Colorectal Liver Metastasis.

Objective: To assess the characteristics of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and investigated whether all KRAS mutations predict poor prognosis in patients with unresectable colorectal liver metastasis (CRLM). Methods: Correlations between KRAS-mutation status and clinicopathological characteristics of 93 patients with unresectable CRLM at our institution between 2010 and 2018 were retrospectively analyzed. Kaplan-Meier and Cox proportional hazard models were used to evaluate the prognostic significance of KRAS mutations. Results:KRAS were primarily single-point mutations, identified in 41.9% of patients. There were no significant differences in clinicopathological characteristics between wild-type KRAS and mutant KRAS. Patients with mutant KRAS had significantly worse overall survival (OS) and progression-free survival (PFS) than those with wild-type KRAS. Moreover, patients with codon 12 mutations had worse OS and PFS than those with wild-type KRAS, whereas mutations in codon 13 were not associated with a worse prognosis. Among the 5 most common mutations in codons 12, G12V, and G12D were associated with worse OS, furthermore, G12C mutation seemed to associated with worse PFS than patients with wild-type KRAS. Conclusion:KRAS codon 12 mutations were predictive for a poor prognosis in patients with unresectable CRLM. G12D and G12V mutations were associated with worse OS, whereas G12C mutation seemed to be associated with decreased PFS.

Large tumor size is a poor prognostic factor of gastric cancer with signet ring cell: Results from the surveillance, epidemiology, and end results database.

There has been a steady increase in the incidence of signet ring cell (SRC) carcinoma, a distinct histological type with cells containing abundant intracytoplasmic mucin. We aimed to analyze the clinicopathological characteristics and prognostic value of patients with SRC gastric cancer (GC) who underwent gastrectomy.Clinical data of 10,312 GC patients who underwent D2 radical gastrectomy were obtained from the Surveillance, Epidemiology, and End Results database and were retrospectively analyzed. X-tile plots were constructed to illustrate the optimal cut-off points using the minimum P-value from the log-rank Chi-squared test. The Kaplan-Meier method was used for the analysis of the overall cumulative probability of survival. Their differences were evaluated using the log-rank test. The Cox multiple factors analysis was performed using the logistic regression method.In total, 946 (9.17%) SRC GC patients with pT1a-4bN0-3bM0 stage cancer were recruited. The optimal cut-off point for size was 49 mm. The 3-year overall survival (OS) rates of the SRC GC, large-size, and small-size groups were 35.89%, 30.63%, and 44.96%, respectively (P < .05). Cox multivariate analysis showed that tumor size (odds ratio [OR] = 2.032), T3 category (OR = 1.324), T4a category (OR = 1.945), and T4b category (OR = 2.163) were independent hazard prognostic factors.SRC GC has a distinct biological behavior, presents as a large-sized tumor (≥49 mm), and is associated with worse outcomes. SRC GC patients have 2.032 times risk of mortality. SRC patients with larger tumors are at higher risk for infiltrative growth, lymph node metastasis, and distant metastasis.

Not all mutations of KRAS predict poor prognosis in patients with colorectal cancer.

The mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS) has been reported to be prognostically important in patients with colorectal cancer (CRC). In this study, we investigated whether all KRAS mutations predict poor prognosis in patients with CRC. Our analysis of characteristics of KRAS mutations revealed the mutation rate for codon 12 was 72.7%, of which G12D was the highest (47.5%) followed by G12V (30.6%), and the mutation rate for codon 13 was 22.0%, of which all were G13D. In support of the concept that prognostic value of the KRAS codon-12 mutations is different from the codon-13 mutations, results from our Cox proportional hazard model studies showed that codon-12 mutations correlated with worse overall survival (OS; HR = 2.846, 95% CI: 1.967-4.118, P < 0.001) and progression free survival (PFS; HR = 2.011, 95% CI: 1.450-2.789, P < 0.001). No prognostic significance was revealed for codon-13 mutations. On further analysis, we found that mortality risk was significantly increased with G12D and G12V (G12D: HR = 2.802, 95% CI: 1.793-4.381, P < 0.001; G12V: HR = 2.802, 95% CI: 1.793-4.381, P < 0.001), as was the risk of disease progression (G12D: HR = 2.079, 95% CI: 1.396-3.099, P < 0.001; G12V: HR = 2.408, 95% CI: 1.517-3.822, P < 0.001). To conclude, our results support the concept that codon-12 mutations were predictive for a poor prognosis in Chinese patients with CRC. Specifically, G12D and G12V were independent prognostic factors for worse OS and PFS.

EYA1 promotes tumor angiogenesis by activating the PI3K pathway in colorectal cancer.

Blood vessels are one of the major routes for the dissemination of cancer cells. Malignant tumors release growth factors such as vascular endothelial growth factor(VEGF) to induce angiogenesis, thereby promoting metastasis. Here, we report that The Drosophila Eyes Absent Homologue 1 (EYA1), which is overexpressed in colorectal tumor cells, can promote colorectal tumor angiogenesis by coordinating with the hypoxia-inducible factor 1 (HIF-1α) to increase the expression of VEGF-A. Moreover, data indicated that the enhancement of HIF-1α expression by Eya1 depended on its ability to activate the phosphatidylinositol 3-kinase (PI3K) signaling pathways to increase the phosphorylation of AKT subunits. Overexpression of Eya1 increased tumor angiogenesis in vivo and in vitro. Our study suggested that Eya1 is essential in regulating cancer cell-mediated angiogenesis and contributes to tumor growth, and that Eya1 provides a potential and specific target for new anti-angiogenesis drug development.