PurposeLaparoscopic gastrectomy is a widely accepted surgical technique. Recently, robotic gastrectomy has been developed, as an alternative minimally invasive surgical technique. This study aimed to evaluate the question of whether robotic gastrectomy is feasible and safe for the treatment of gastric cancer, due to its learning curve.Materials and MethodsWe retrospectively reviewed the prospectively collected data of 100 consecutive robotic gastrectomy patients, from November 2008 to March 2011, and compared them to 282 conventional laparoscopy patients during the same period. The robotic gastrectomy patients were divided into 20 initial cases; and all subsequent cases; and we compared the clinicopathological features, operating times, and surgical outcomes between the three groups.ResultsThe initial 20 robotic gastrectomy cases were defined as the initial group, due to the learning curve. The initial group had a longer average operating time (242.25±74.54 minutes vs. 192.56±39.56 minutes, P>0.001), and hospital stay (14.40±24.93 days vs. 8.66±5.39 days, P=0.001) than the experienced group. The length of hospital stay was no different between the experienced group, and the laproscopic gastrectomy group (8.66±5.39 days vs. 8.11±4.10 days, P=0.001). The average blood loss was significantly less for the robotic gastrectomy groups, than for the laparoscopic gastrectomy group (93.25±84.59 ml vs. 173.45±145.19 ml, P<0.001), but the complication rates were no different.ConclusionsOur study shows that robotic gastrectomy is a safe and feasible procedure, especially after the 20 initial cases, and provides a satisfactory postoperative outcome.

Pluripotent stem cells (PSCs) have distinct metabolic properties that support their metabolic and energetic needs and affect their stemness. In particular, high glycolysis is critical for the generation and maintenance of PSCs. However, it is unknown how PSCs maintain and acquire this metabolic signature. In this study, we found that core pluripotency factors regulate glycolysis directly by controlling the expression of glycolytic enzymes. Specifically, Oct4 directly governs Hk2 and Pkm2, which are important glycolytic enzymes that determine the rate of glycolytic flux. The overexpression of Hk2 and Pkm2 sustains high levels of glycolysis during embryonic stem cell (ESC) differentiation. Moreover, the maintenance of high glycolysis levels by Hk2 and Pkm2 overexpression hampers differentiation and preserves the pluripotency of ESCs in the absence of leukemia inhibitory factor. Overall, our study identifies a direct molecular connection between core pluripotency factors and ESC metabolic signatures and demonstrates the significance of metabolism in cell fate determination. STEM CELLS 2015;33:2699-2711 SIGNIFICANCE STATEMENTAlthough distinct metabolic properties are critical for the generation and maintenance of Pluripotent stem cells (PSCs), it is unknown how PSCs maintain and acquire this metabolic signature. In this study, we found that core pluripotency factors regulated glycolysis directly by targeting key glycolytic enzymes in embryonic stem cells (ESCs). Furthermore, we found that sustainment of high glycolytic flux delays ESC differentiation and enables certain populations of ESCs to retain the capacity for self-renewal and differentiation potential in the absence of LIF, demonstrating the significance of metabolism in stemness regulation and cell fate determination.

For cells to exit from pluripotency and commit to a lineage, the circuitry of a core transcription factor (CTF) network must be extinguished in an orderly manner through epigenetic modifications. However, how this choreographed epigenetic remodeling at active embryonic stem cell (ESC) genes occurs during differentiation is poorly understood. In this study, we demonstrate that C-terminal binding protein 2 (Ctbp2) regulates nucleosome remodeling and deacetylation (NuRD)-mediated deacetylation of H3K27 and facilitates recruitment of polycomb repressive complex 2 (PRC2)-mediated H3K27me3 in active ESC genes for exit from pluripotency during differentiation. By genomewide analysis, we found that Ctbp2 resides in active ESC genes and co-occupies regions with ESC CTFs in undifferentiated ESCs. Furthermore, ablation of Ctbp2 effects inappropriate gene silencing in ESCs by sustaining high levels of H3K27ac and impeding H3K27me3 in active ESC genes, thereby sustaining ESC maintenance during differentiation. Thus, Ctbp2 preoccupies regions in active genes with the NuRD complex in undifferentiated ESCs that are directed toward H3K27me3 by PRC2 to induce stable silencing, which is pivotal for natural lineage commitment. STEM CELLS 2015;33:2442-2455 SIGNIFICANCE STATEMENTWhile the pluripotent state is molecularly well defined, much less is known about the molecular mechanisms acting at the end of pluripotency. The goal of our study was to explore the epigenetic role of Ctbp2 in establishing ESC identity during exit from pluripotency. We demonstrated that Ctbp2 preoccupies regions in active ESC genes, and balances proper H3K27ac levels with NuRD complex and appropriate H3K27me3 levels via PRC2 at these loci during exit from pluripotency. Our study helps shed light on the epigenetic changes at the end of pluripotency, ultimately leading to understanding natural lineage commitments.

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