No abstract

The investigation of prognostic factor for gastric cancer is still desirable because of dismal prognosis in gastric cancer. Lauren's classification is currently a useful histological classification. There are few large series evaluating the prognostic significance of Lauren's classification in gastric cancer. From January 1987 to December 2013, a total of 3071 patients received gastrectomy for gastric cancer. According Lauren's classification, 1423(46.3%) patients were intestinal type, 1000 patients (32.6%) were diffuse type, and 648 patients (21.1%) were mixed type. The clinicopathological characteristics and prognosis in Lauren's classification were analyzed in these patients. Our results showed that patients with intestinal type gastric cancer (57.7%) had a better 5-year overall survival than diffuse type (45.6%) and mixed type (43.4%, P < 0.001). The clinicopathological characteristics showed that gastric cancer patients with intestinal type were older (P < 0.001), male predominant (P < 0.001), smaller tumor size (P < 0.001), distal stomach predominant (P < 0.001), relative well differentiated (P < 0.001), less advanced Borrmann type (P < 0.001), less scirrhous type stromal reaction(P < 0.001), less infiltrating type of Ming's histology type(P < 0.001), less tumor invasion depth and less lymphovascular invasion (P < 0.001). Multivariate analysis with overall survival as an endpoint showed that age (P = 0.005), Borrmann classification (P < 0.001), pathological T category (P = 0.023), pathological N category (P < 0.001) and Lauren's classification (P = 0.003) were significant correlated in gastric cancer. Lauren's classification is an independent prognostic factor in gastric cancer patient undergoing gastrectomy. Lauren's classification can serve as a prognostic marker for gastric cancer patient receiving gastrectomy. The clinicopathological appearance and prognosis of mixed type gastric cancer is similar to diffuse type gastric cancer.

Robotic gastrectomy could achieve extended lymph node dissection similar to open surgery. Our results showed a significant learning curve effect in the initial 25 cases of the robotic group.

Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. To establish a Gnmt knockout mouse model, 2 lambda phage clones containing a mouse Gnmt genome were isolated. At 11 weeks of age, the Gnmt؊/؊ mice had hepatomegaly, hypermethioninemia, and significantly higher levels of both serum alanine aminotransferase and hepatic S-adenosylmethionine. Such phenotypes mimic patients with congenital GNMT deficiencies. A real-time polymerase chain reaction analysis of 10 genes in the one-carbon metabolism pathway revealed that 5,10-methylenetetrahydrofolate reductase, S-adenosylhomocysteine hydrolase (Ahcy), and formiminotransferase cyclodeaminase (Ftcd) were significantly down-regulated in Gnmt؊/؊ mice. This report demonstrates that GNMT regulates the expression of both Ftcd and Ahcy genes. Results from pathological examinations indicated that 57.1% (8 of 14) of the Gnmt؊/؊ mice had glycogen storage disease (GSD) in their livers. Focal necrosis was observed in male Gnmt؊/؊ livers, whereas degenerative changes were found in the intermediate zones of female Gnmt؊/؊ livers. In addition, hypoglycemia, increased serum cholesterol, and significantly lower numbers of white blood cells, neutrophils, and monocytes were observed in the Gnmt؊/؊ mice. A real-time polymerase chain reaction analysis of genes involved in the gluconeogenesis pathways revealed that the following genes were significantly down-regulated in Gnmt؊/؊ mice: fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphate transporter. Conclusion: Because Gnmt؊/؊ mice phenotypes mimic those of patients with GNMT deficiencies and share several characteristics with GSD Ib patients, we suggest that they are useful for studies of the pathogenesis of congenital GNMT deficiencies and the role of GNMT in GSD and liver tumorigenesis.

Purpose: Persistent interleukin-8 (IL-8) production contributes to chronic inflammation of the stomach. The proinflammatory IL-1h polymorphisms, which enhance the cytokine production, are associated with increased risk of gastric cancer. The À251A/T polymorphism of the IL-8 promoter is involved in several human diseases. Particularly, the À251A is associated with decreased risk of colorectal cancer. We aimed to determine whether the À251 allele resulting in high IL-8 expression was associated with increased risk of gastric carcinoma. Experimental Design: The À251A/T promoters were cloned and analyzed by luciferase assay. Binding of nuclear proteins to the À251A/T promoters was analyzed by electrophoretic mobility shift assay.The À251A/T promoters were differentiated by PCR-RFLP. Comparison of gastric cancer risk between the À251A/T promoters was done by a case-control study. Results:The À251Tallele possessed transcriptional activity 2-to 5-fold stronger than the À251A counterpart. Electrophoretic mobility shift assay showed that the À251A promoter had strong ability to bind to an unknown protein or multiprotein complex. The À251T allele was associated with increased risk of noncardia (P trend = 0.012) and cardia (P trend = 0.029) carcinomas. Gastric carcinoma patients with the low-risk AA genotype had a tendency to sustain intestinal-type carcinomas (m 2 = 6.816; P = 0.033); however, the high-risk À251Tallele was associated with >2-fold increased risk of diffuse-type (AA versus AT + TT: odds ratio, 2.52; 95% confidence interval,1.16-5.49; P = 0.017) and mixed-type (AA versus AT + TT: odds ratio, 2.22; 95% confidence interval, 1.12-4.40; P = 0.019) carcinomas. Conclusions:The IL-8 À251Tallele is significantly associated with increased risk of gastric carcinoma, particularly the diffuse and mixed types in Chinese population.