BackgroundAccording to the Lauren classification, gastric adenocarcinomas are divided into diffuse and intestinal types. The causative attribution explaining the dismal prognosis of diffuse-type remains unknown.MethodsWe examined the archive of 1000 patients with gastric adenocarcinomas who received radical gastrectomy in our center and assessed the effect of the Lauren classification on survival in a multivariate approach. Moreover we compared the variation of clinical features between the diffuse-type and intestinal-type and explored the contributing factors for the prognostic difference.ResultsThere were 805 resectable patients for the final analysis. Diffuse-type comprised of 48.7% in the gastric carcinoma in our group and showed poorer prognosis than intestinal-type (P=0.013). Multivariate analysis revealed that independent prognostic factors for gastric carcinoma patients were T stage (P<0.001), N stage (P<0.001) tumor size (P<0.001) and Lauren classification (P=0.003). For the clinical features, diffuse-type was significantly associated with younger age (p<0.001), female preponderance (p <0.001), distal location (P<0.001), advanced pT (p < 0.001), advanced pN (p < 0.001) and advanced TNM stage (p = 0.027).ConclusionsDiffuse type adenocarcinoma carries a worse prognosis that may be partially explained by the tendency of this subtype to present at more advanced T and N stage. However, Lauren classification has prognostic significance that is independent of T and N stage as well as other prognostic variables based on the multivariate cox analysis.
The aim of present study was to examine whether the C-reactive protein (CRP)-based systemic inflammatory response such as the Glasgow Prognostic Score (GPS; a combination of CRP and albumin) offers prognostic value that is superior to the circulating white cellular components as neutrophil/lymphocyte ratio (NLR) or platelet/lymphocyte ratio (PLR) in patients undergoing resection for stage III gastric cancer. The medical records of 324 patients with stage III gastric adenocarcinoma were reviewed. Potential prognosis factors were evaluated with the Kaplan-Meier methodology and multivariable Cox hazards model. An increase of GPS was associated with an increase weight loss, higher NLR, higher PLR, and larger tumor size. On multivariate analysis, only the GPS, tumor-nodes-metastasis staging, and adjuvant chemotherapy were associated independently with disease-free and overall survival. However, the NLR and PLR were not. In subgroup analysis, patients with a GPS of 2 had a significantly poorer median survival (13.70 months) when compared with patients with a GPS of 1 (27.4 months) or 0 (median survival had not been reached) in patients who had received adjuvant chemotherapy. Our study demonstrated that elevated preoperative GPS is superior to circulating white cellular components and was associated with reduced overall and disease-free survival for patients with stage III gastric cancer.
ObjectiveTo monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer (mGC).DesignTargeted sequencing of 416 clinically relevant genes was performed in 78 paired plasma and tissue biopsy samples to determine plasma-tissue concordance. Then, we performed longitudinal analyses of 97 serial plasma samples collected from 24 patients who were HER2+ to track the resistance during trastuzumab treatment and validated the identified candidate resistance genes.ResultsThe results from targeted sequencing-based detection of somatic copy number alterations (SCNA) of HER2 gene were highly consistent with fluorescence in situ hybridisation data, and the detected HER2 SCNA was better than plasma carcinoembryonic antigen levels at predicting tumour shrinkage and progression. Furthermore, most patients with innate trastuzumab resistance presented high HER2 SCNA during progression compared with baseline, while HER2 SCNA decreased in patients with acquired resistance. PIK3CA mutations were significantly enriched in patients with innate resistance, and ERBB2/4 genes were the most mutated genes, accounting for trastuzumab resistance in six (35.3%) and five (29.4%) patients in baseline and progression plasma, respectively. Patients with PIK3CA/R1/C3 or ERBB2/4 mutations in the baseline plasma had significantly worse progression-free survival. Additionally, mutations in NF1 contributed to trastuzumab resistance, which was further confirmed through in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade overcame trastuzumab resistance.ConclusionLongitudinal circulating tumour DNA sequencing provides novel insights into gene alterations underlying trastuzumab resistance in HER2+mGC.
Little is known about the role of association between ABO blood type and risk of pancreatic cancer develops through effects on hepatitis B viral (HBV) infection. Our study aimed to determine whether joint ABO blood type and HBV infection could increase the risk for pancreatic cancer. A total of 645 patients with pancreatic adenocarcinoma and 711 age-and sex-matched individuals who had nonmalignant diseases treated at the Sun Yat-sen University Cancer Center in China were retrospectively analyzed. Blood samples were tested for ABO blood type and hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), hepatitis B e antibody (anti-HBe) and hepatitis B core antibody (anti-HBc). Multivariable unconditional logistic regression analysis was used to estimate adjusted odds ratios [AORs] and 95% confidence interval [CI]. Multivariable analysis with adjustment for risk factors showed that A blood type, HBsAg-positive/anti-HBcpositive, anti-HBs-positive/anti-HBc-positive were significantly associated with pancreatic cancer. The estimated AORs (95% CI) were as follows: A blood type, 1.425 (1.071-1.894), HBsAg-positive/anti-HBc-positive, 1.610 (1.125-2.304), anti-HBspositive/anti-HBc-positive, 1.526 (1.159-2.011). The effect of A blood type significantly modified the risk of pancreatic cancer among subjects with anti-HBc-positive (AORs 5 1.882, 95% CI, 1.284-2.760). In our study, we reported an association between A blood type, infection with HBV and pancreatic cancer risk. Moreover, we found a synergism between A blood type and HBV infection in the development of pancreatic cancer.Pancreatic cancer is the fifth most common cancer and the fourth leading cause of cancer-related mortality worldwide.
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