Akira Naruke

Many malignant tumors consist of heterogeneous subpopulations of cells. This heterogeneity is associated with genetic characteristics. However, it remains unclear whether gene expression levels differ among specific sites of tumors in gastric cancer.

56 Background: The biopsy specimen by endoscopy can only show the surface of its gene profiles. We hypothesis whether the biopsy specimen can reflect all part of gene profile or not. We tested how 5-FU related genes and angiogenesis gene expressed in the invasion depth in the primary tumor of the Stage II or III advanced gastric cancer. Methods: Twenty-five patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed.Formalin-fixed, paraffin-embedded tumor tissues were dissected from the surface section (mainly mucosa), the middle section (mainly submucossa) and the deep section (the part invaded most deeply) of the primary tumor and the normal gastric mucosa tissue by the laser-captured microdissection technique and were analyzed for target gene expressions using a quantitative real-time polymerase chain reaction.We analyzed for target genes as TS, TP, DPD, ERCC1, EGFR, VEGF and HIF1α. Results: In the primary tumor, TP and HIF1α gene expression in the surface section was significantly higher than in the deep section (p=0.021, p=0.012). These gene expression and the depth of the primary tumor had a correlation coefficient (TP; r=0.29, HIF1α; r=0.33). There was no significantly difference between surface and deep section in the primary tumor in TS, DPD, ERCC1, VEGF, EGFR except TP and HIF1α. There was no significantly difference between surface and middle section in the primary tumor in all gene expression. There was no significantly difference between middle and deep section in the primary tumor in all gene expression. Conclusions: Only TP and HIF1α had tendency that these gene expression became higher as invaded from the surface section to the deep section of primary tumor. These data suggested that biopsy specimens could be predicted gene expression profile from the surface of gastric cancer. But as you know, gastric cancer has a heterogeneity gene profile. We need at least few samples to say whole gene expression of its tumors. This is preliminary data, it will need further study to proof these result.

In patients with carcinomatous peritonitis caused by the invasion and peritoneal dissemination of gastrointestinal cancer, disease progression can trigger complications such as ileus, ascites, and hydronephrosis.Anorexia, impaired oral intake, nausea, vomiting, abdominal pain, abdominal bloating, anuria, and other symptoms can develop, negatively affecting patients' general condition and quality of life.The treatment of carcinomatous peritonitis is an important determinant of outcomes, but the guidelines for its diagnosis, the evaluation of its response to chemotherapy, and the question of which standard therapy to apply remain unestablished.In recent years, however, clinical trials have attempted to evaluate the benefits of systemic chemotherapy and the intraperitoneal administration of drugs such as cisplatin and paclitaxel in patients with advanced or recurrent gastric cancer who have peritoneal dissemination.In the field of palliative therapy, octreotide has been approved in Japan for the amelioration of symptoms associated with gastrointestinal obstruction.Such treatment is expected to contribute substantially to improving patients' quality of life.

The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to be the most effective treatment for advanced gastric cancer in the United States, Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently considered to be the first candidate as the standard drug for advanced gastric cancer. S-1 based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes, are expected to yield good results. Above all, S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable frontline standard for patients with AGC. We therefore need to develop new agents and combination chemotherapy regimens to achieve a greater survival benefit in AGC.