Purpose : Population-based data on the proportion and prognosis of liver metastases at diagnosis of gastric cancer are currently lacking. Besides, the treatment of gastric cancer with liver metastases is still controversial now. Methods : Patients with gastric cancer and liver metastases (GCLM) at the time of diagnosis in advanced gastric cancer were identified using the Surveillance, Epidemiology, and End Result (SEER) database of the National Cancer Institute. Multivariable logistic and Cox regression were performed to identify predictors of the presence of GCLM at diagnosis and factors associated with all-cause mortality. Results : We identified 3507 patients with gastric cancer and liver metastases at the time of diagnosis, representing 16.89% of the entire cohort and 44.12% of the subset with metastatic disease to any distant site. Among entire cohort, multivariable logistic regression identified thirteen factors (age, race, sex, original, tumor location, pathology grade, Lauren classification, T staging, N staging, tumor size, number of extrahepatic metastatic sites to bone, lung, and brain, insurance situation and smoking) as predictors of the presence of liver metastases at diagnosis. Median survival among the entire cohort with GCLM was 4.0 months (interquartile range: 1.0-10.0 mo). Patients receiving comprehensive therapy had longer median overall survival, of which the median survival was 12.0 months (interquartile range: 6.0-31.0 mo). Multivariable Cox model in SEER cohort confirmed nine factors (age, tumor location, Lauren classification, T staging, number of extrahepatic metastatic sites to bone, lung, and brain, surgery, chemotherapy, RSC and marital status) as independent predictors for overall survival. Conclusions : The findings of this study provided population-based estimates of the proportion and prognosis for LM at time of GC diagnosis. These findings provide preventive guidelines for screening and treatment of LM in GC patients.
ObjectiveThe aim of this study is to identify prognostic imaging biomarkers and create a radiogenomics nomogram to predict overall survival (OS) in gastric cancer (GC).MaterialRNA sequencing data from 407 patients with GC and contrast-enhanced computed tomography (CECT) imaging data from 46 patients obtained from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) were utilized to identify radiogenomics biomarkers. A total of 392 patients with CECT images from the Nanfang Hospital database were obtained to create and validate a radiogenomics nomogram based on the biomarkers.MethodsThe prognostic imaging features that correlated with the prognostic gene modules (selected by weighted gene coexpression network analysis) were identified as imaging biomarkers. A nomogram that integrated the radiomics score and clinicopathological factors was created and validated in the Nanfang Hospital database. Nomogram discrimination, calibration, and clinical usefulness were evaluated.ResultsThree prognostic imaging biomarkers were identified and had a strong correlation with four prognostic gene modules (P < 0.05, FDR < 0.05). The radiogenomics nomogram (AUC = 0.838) resulted in better performance of the survival prediction than that of the TNM staging system (AUC = 0.765, P = 0.011; Delong et al.). In addition, the radiogenomics nomogram exhibited good discrimination, calibration, and clinical usefulness in both the training and validation cohorts.ConclusionsThe novel prognostic radiogenomics nomogram that was constructed achieved excellent correlation with prognosis in both the training and validation cohort of Nanfang Hospital patients with GC. It is anticipated that this work may assist in clinical preferential treatment decisions and promote the process of precision theranostics in the future.
The IGF1 signal pathway is highly activated in some subtype of gastric cancer(GC) that exhibits poor survival and chemotherapy resistance. Although the results of clinical trials of anti-IGF1R monoclonal antibodies and IGF-1R inhibitors have been mostly disappointing in unselected cancer patients, some patients benefit from anti-IGF1R therapy in these failed studies. Therefore, it is necessary to characterize the complex IGF signaling in GC and help refine the strategies targeting the IGF1 pathway. We found that GC cell lines exhibit differential responses to the specific IGF1R inhibitor OSI906. According to the phosphorylation status of Akt upon the OSI906 treatment, we divided the GC cell lines into IGF1R-dependent and IGF1R-independent cells. Both in vitro and in vivo experiments indicate that Dox-induced knockdown of NEDD4 significantly suppresses tumor growth of IGF1R-dependent GC cells and NEDD4 overexpression promotes tumor growth of IGF1R-dependent GC cells. In contrast, the proliferation of IGF1R-independent GC cells is not affected by NEDD4 silencing and overexpression. The rescue experiments show that a PTEN-IRS1 axis is required for NEDD4-mediated regulation of Akt activation and tumor growth in GC cells. Clinically, NEDD4 is expressed higher in IGF1-high GC tissues compared with IGF1-low GC tissues and normal tissues, and the co-high expression of NEDD4 and IGF1 predicts a worse prognosis in GC patients. Taken together, our study demonstrated that NEDD4 specifically promotes proliferation of GC cells dependent on IGF1/IGF1R signaling by antagonizing the protein phosphatase activity of PTEN to IRS1, and targeting NEDD4 may be a promising therapeutic strategy for IGF1 signal pathway-driven gastric cancer.
Background The overlap guiding tube (OGT) method, which was designed by our team to assist in overlap esophagojejunostomy, could potentially provide new perspectives for esophagojejunostomy. The application of the OGT-assisted method was first explored by our team and has not yet been reported. Methods This cohort study analyzed the 3 month outcomes of 38 gastric/gastroesophageal junction (G/GEJ) tumor patients who underwent OGT-assisted overlap esophagojejunostomy. Results There were 27 males and 11 females, aged 40–82 years. All patients underwent surgery successfully. The success rate of inserting anvil fork into esophageal lumen at first attempt was 97.4%. The total operation time, esophagojejunostomy time, volume of intraoperative blood loss, and length of surgical incision were 317.6 ± 51.5 min, 20.8 ± 3.8 min, 50.0 (range 15.0–200.0) ml, and 5.0 (range 4.0–8.0) cm, respectively. No procedures were converted to other laparoscopic anastomosis techniques or open approaches. The time to postoperative initial flatus, liquid diet intake, soft diet intake, and length of postoperative hospital stay were 3.0 (range 1.0–6.0) days, 4.0 (range 2.0–9.0)days, 6.0 (range 3.0–11.0) days, and 8.5 (range 6.0–16.0) days, respectively. Overall, postoperative complications were observed in 8 (21.1%) patients. Among them, one patients developed esophagojejunal anastomotic leakage. After 3 months of follow-up, none of the patients developed anastomotic stenosis or experienced unplanned secondary surgery or perioperative death. Conclusions OGT-assisted overlap esophagojejunostomy for patients with G/GEJ tumors is safe and feasible, with good short-term effects. OGT method has a satisfactory success rate of inserting anvil fork into esophageal lumen at first attempt and could prevent from developing esophageal submucosa pseudocanals.
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