menaquinone-6 and Stomach-Neoplasms

We experienced a case of epidural hematoma caused by coagulopathy 3 days after surgery. A 72-year-old man, who had undergone a total gastrectomy, suffered from nausea and vomiting by ileus. He underwent repair of ileus under general anesthesia with thoracic epidural anesthesia. Three days after surgery, abnormal bleeding followed by disorder of prothrombin activity (PT) and activated partial thromboplastin time (aPTT) and paralysis due to thoracic epidural hematoma developed. It was suspected that these coagulopathies were the results of vitamin K deficiency. Vitamin K deficiency in this patient was considered to have been caused by cephem antibiotics containing N-methyl-thiotetrazole (NMTT) side chain and no oral intake of food for a few days preoperatively. The patient was treated with fresh frozen plasma and intravenous menatetrenon, which improved abnormal bleeding and disorder of PT and aPTT within 24hr. After a discussion with orthopedic consultants, we selected a conservative therapy rather than surgical removal of the hematoma. Thoracic epidural hematoma disappeared two months after surgery, but motor paralysis requiring rehabilitation remained. In conclusion, when patients have not eaten anything for a few days and antibiotics with an NMTT sidechain has been administered, care must be taken to prevent vitamin K deficiency and coagulopathy.

Topics: Aged; Anesthesia, Epidural; Anesthesia, General; Carbapenems; Gastrectomy; Hematoma, Epidural, Spinal; Humans; Ileus; Infusions, Intravenous; Male; Plasma; Postoperative Complications; Stomach Neoplasms; Tetrazoles; Vitamin K 2; Vitamin K Deficiency

Vitamin K2 (VK2) has a growth inhibitory effect on various types of cancer cells in vitro, and its efficacy has been demonstrated in clinical applications in a number of patients with leukemia and hepatocellular carcinoma. In this study, the effect of cell growth inhibition and apoptosis induction and the concomitant use of an anticancer agent by VK2 (menaquinone: MK4), on gastric cancer cell lines were examined. When 4 kinds of gastric cancer cells (KATO III, MKN7, MKN74 and FU97) were exposed to MK4, the cell growth was inhibited in an MK4 dose-dependent manner. Morphologically, apoptosis induced by MK4 was recognized in FU97, but only a slight number of apoptotic images was recognized in other cell lines. On the contrary, in all the cell lines, the percentage of APO2.7 positive cells increased significantly in the MK4-treated group as compared to the controls. Caspase-3 activity increased significantly in KATO III and FU97 as compared to the controls, while no significant differences were noted in MKN7 or MKN74. Moreover, in all the cell lines, the percentage of G0/G1-phase cells ( approximately 70% in KATO III and FU97, and > or =80% in MKN7 and MKN74) increased in comparison to the controls, suggesting that cell-cycle arrest had occurred. All of the gastric cancer cell lines were given MK4 in different concentrations and two kinds of anticancer agent, with the result that cell growth was inhibited by the anticancer agent in a dose-dependent manner when it was given with MK4 in concentrations of up to 10 microM. In conclusion, our results demonstrate that the effect of MK4 on apoptosis and cell-cycle arrest differs in differentiated (MKN7, MKN74) and undifferentiated (KATO III, FU97) gastric cancer cell lines, and that MK4 alone or with anticancer agents has an antitumor effect on gastric cancer cell lines.

Topics: Antibodies; Antineoplastic Agents; Apoptosis; Caspase 3; Caspases; Cell Cycle; Cell Line, Tumor; Docetaxel; Humans; Stomach Neoplasms; Taxoids; Vitamin K 2