Toshiki Yamashita

Methylated TMS1 and DAPK genes predict prognosis and response to chemotherapy in gastric cancer.

Gastric cancer is the second most common cause of cancer deaths worldwide. The identification of molecular genetic parameters that are associated with response to chemotherapy and prognosis is of utmost interest. We examined methylation of the apoptosis‐related genes, TMS1 and DAPK, in 81 primary gastric cancers using methylation‐specific PCR and compared their methylation status with clinicopathological findings. Aberrant methylation of TMS1 and DAPK genes was detected in 26 (32.1%) tumors and in 18 (22.2%) tumors, respectively. The overall survival of patients with both methylated genes was significantly shorter compared with those with only one methylated gene or no methylated genes (p = 0.0003). Neither gene methylation had any relation to other clinicopathological findings. Next, we examined 43 patients treated by 5‐fluorouracil–based chemotherapy, who had distant metastasis or recurrence after radical resection, to determine the relation between chemosensitivity and methylation. The response rate was lower in patients with either methylation than without (TMS1: 22.2% vs. 48.0%; DAPK: 21.4% vs. 44.8%). Overall survival tended to be shorter in the patients with both methylations compared with either or no methylations (p = 0.0806). The time to progression of patients with methylation of TMS1 or DAPK was significantly shorter than patients without methylation (TMS1: p = 0.0123; DAPK: p = 0.0464). Furthermore, the time to progression of patients with both methylated genes was significantly shorter than patients with one methylation or no methylation (p = 0.0082). In conclusion, TMS1 and DAPK methylation might predict the prognosis and response to chemotherapy in gastric cancer.

Is lymphadenectomy needed for all submucosal gastric cancers

OBJECTIVE To find out if it is feasible to extend the indication for local resection of submucosal gastric cancer without increasing the risk of lymph node metastases. DESIGN Retrospective study. SETTING University hospital, Japan. SUBJECTS 104 patients with gastric cancer confined to the submucosal layer who underwent conventional gastrectomy with lymphadenectomy. INTERVENTIONS The risk of nodal metastases was analysed retrospectively depending on the depth of submucosal invasion, size of the tumour, and other clinicopathological findings. MAIN OUTCOME MEASURES The degree of submucosal invasion, size of the tumour, and incidence of lymph node metastasis. RESULTS 15/104 patients (14%) had lymph node metastases. No patient in whom submucosal invasion was less than 500 microm or tumour was less than 15 mm in diameter developed lymph node metastases. Fewer patients had lymphatic permeation (37/89) and venous involvement (21/89) in the group without lymph node metastases. CONCLUSION These data seem to support the hypothesis that early, minimally invasive, gastric cancer measuring < 15 mm in diameter could be treated by endoscopic mucosal or local resection, and gastrectomy with lymphadenectomy might be unnecessary.

Effect of Intra-Arterial Injection of Mitoxantrone-Lipiodol Emulsion on Hepatocellular Carcinoma

The effect of intra-arterial injection of mitoxantrone emulsified with ethiodized oil was investigated in 24 patients with hepatocellular carcinoma. After treatment, 6 of the patients underwent hepatectomy. In 18 unresected cases, there were 8 (44%) partial responses, which had continued 2 to 10 months (mean, 7.4 months). In the remaining 6 resected cases, the necrotic areas in the main nodules accounted for 65% (mean, 85%) of the nodule, with complete necrosis in three cases. The results in this preliminary study are encouraging to further study.