Cancer cells alter their metabolism for the production of precursors of macromolecules. However, the control mechanisms underlying this reprogramming are poorly understood. Here we show that metabolic reprogramming of colorectal cancer is caused chiefly by aberrant MYC expression. Multiomics-based analyses of paired normal and tumor tissues from 275 patients with colorectal cancer revealed that metabolic alterations occur at the adenoma stage of carcinogenesis, in a manner not associated with specific gene mutations involved in colorectal carcinogenesis. MYC expression induced at least 215 metabolic reactions by changing the expression levels of 121 metabolic genes and 39 transporter genes. Further, MYC negatively regulated the expression of genes involved in mitochondrial biogenesis and maintenance but positively regulated genes involved in DNA and histone methylation. Knockdown of MYC in colorectal cancer cells reset the altered metabolism and suppressed cell growth. Moreover, inhibition of MYC target pyrimidine synthesis genes such as CAD, UMPS, and CTPS blocked cell growth, and thus are potential targets for colorectal cancer therapy.ne of the prominent characteristics of rapidly growing tumor cells is their capacity to sustain high rates of glycolysis for ATP generation irrespective of oxygen availability, termed the Warburg effect (1). Recent studies have shown that cancer cells shift metabolic pathways to facilitate the uptake and incorporation of abundant nutrients, such as glucose and glutamine (2, 3), into cell building blocks, such as nucleotides, amino acids, and lipids, that are essential for highly proliferating cells (4). This seems to be a universal characteristic of highly malignant tumors (5), independent of their carcinogenetic origin (6). Understanding how cancer cells reprogram metabolism can stimulate the development of new approaches in cancer therapy.Although there is now substantial information about how these pathways are regulated, most existing studies on cancer metabolism have used in vitro cell lines. In addition to genetic and epigenetic alterations, altered tumor microenvironment (e.g., blood flow, oxygen and nutrient supply, pH distribution, redox state, and inflammation) plays a profound role in modulating tumor cell metabolism (7-9). Therefore, a systematic characterization of in vivo metabolic pathways was deemed necessary to understand how metabolic phenotypes are regulated in intact human tumors.Here we applied multiomics-based approaches [i.e., metabolomics, target sequencing of cancer-related genes, transcriptomics, and methylated DNA immunoprecipitation sequencing (MeDIPseq)] to paired normal and tumor tissues obtained from 275 patients with colorectal cancer (CRC) and uncovered the details of which factors contributed, and when they contributed, to metabolic reprogramming in colorectal cancer. The results were confirmed by analysis of colorectal tissue from Apc mutant mice and cancer cell lines.

Background The incidence of gastric cancer has been increasing among elderly persons in Japan. This study aimed to clarify risk factors for postoperative complications in oldest old patients with gastric cancer. Methods One-hundred ninety patients more than 75 years old with gastric cancer underwent gastrectomy between 2000 and 2011. Patients were classified into two groups: group A included 29 patients who were 85 years or older (oldest old patients), and group B included 161 patients who were 75-84 years of age. Perioperative parameters associated with complications were compared in each group. Results The preoperative estimated glomerular filtration rate was significantly lower in group A (p = 0.03). The two groups significantly differed in performance status (p = 0.018). Patients in group A received a lesser extent of lymph node dissection and had fewer lymph nodes excised. As a result, the duration of the operation was significantly shorter in group A. There were no significant differences in the frequency or grade of total complications or mortality between the two groups. Operative hemorrhage ([300 ml) and Hiroshima POSSUM (predicted morbidity risk [40) were risk factors in both groups A and B; the risk factors of preoperative serum albumin level and prognostic nutritional index (PNI) were specific to group A.Conclusions Adjustments to the extent of surgery among oldest old patients most likely reduces the incidence of postoperative complications in this group. Preoperative serum albumin level and PNI are significant predictors of postoperative complications in oldest old patients with gastric cancer.

Pancreatic thickness is a significant independent risk factor for PF development after DP with an endopath stapler. The stapler technique is thus considered to be an appropriate modality in patients with a pancreatic thicknesses of <16 mm.

LVI detected by D2-40 is important for the prediction of lymph node metastasis.

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