Characteristics and prognosis of synchronous multiple early gastric cancer

AIM:To assess the clinicopathologic characteristics,risk factors,and prognosis for synchronous multiple early gastric cancer(SMGC).METHODS:A total of 146 patients with SMGC and1194 patients with single gastric cancer who had undergone gastrectomy between 1989 and 2008 were retrospectively analyzed to determine their clinicopathologic characteristics and postoperative survival.Tumors were classified into groups on the basis of location and histology.Smoking habits were evaluated using the Brinkman index.Clinical and pathological factors were compared using either Fisher’s exact test or Pearson’sχ2test.Logistic regression analysis was performed to identify independent risk factors.Survival rate was calculated using the Kaplan-Meier method.RESULTS:SMGCs accounted for 10.9%of gastric cancer cases and occurred predominantly in elderly male patients with a family history of gastric cancer who were both smokers and drinkers.These tumors were typically macroscopically elevated and histologically differentiated.There were no significant differences between SMGC and single gastric cancer patients with respect to tumor location,tumor size,lymph node metastasis,the number of metastatic lymph nodes,venous invasion,or tumor stage(P=0.052,P=0.347,P=0.595,P=0.805,P=0.559,and P=0.408,respectively).Further,there was no significant difference in postoperative survival between the patient groups(P=0.200).Of the 146SMGC patients,a single patient had remnant cancer.CONCLUSION:A careful preoperative endoscopy is necessary for patients who are at high risk of SMGC,and minimally invasive treatment may be indicated in some cases.

Molecular targeting to treat gastric cancer

Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.

Molecular targeting therapy using bevacizumab for peritoneal metastasis from gastric cancer

AIM: To clarify the significance of vascular endothelial growth factor(VEGF) in peritoneal metastasis from gastric cancer, using the gastric cancer cell line MKN-45 compared with the high potential peritoneal dissemination gastric cancer cell line MKN-45 P. METHODS: The supernatant of culture medium of MKN-45 cells or MKN-45 P cells was collected and the concentrations were measured of various cytokines, matrix metalloproteinases, growth factor and angiogenic factors, including VEGF. We performed an initial pilot study to explore whether bevacizumab, a humanized monoclonal antibody against VEGF, had any suppressive effect on the peritoneal dissemination from gastric cancer in an experimental nude mouse modelof peritoneal metastasis. RESULTS: The concentrations of interleukin-6(IL-6), IL-8, VEGF and matrix metalloproteinase-2 protein in the culture supernatant were each significantly higher than each of those for MKN-45. In the in vivo study, the volume of ascites and the mitotic index were significantly lower in the therapy group than in the nontherapy group. The survival curve of the therapy group was significantly higher than that of the non-therapy group. These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer. CONCLUSION: Findings suggested that bevacizumab for inhibiting VEGF could suppress peritoneal dissemination from gastric cancer.

Relevance of Surgery in Stage IV Gastric Carcinoma

New anticancer drugs are being increasingly used for advanced and recurrent gastric cancer in many institutions. Therefore, the relative importance of surgery may have changed, and there may also be controversy as to whether patients with stage IV gastric cancer should or not undergo surgical resection. The relevance of surgery in this population was studied. The relevance of surgery was studied in 304 cases of stage IV gastric cancer who were treated at KurumeUniversityHospitalfrom 1995 to 2009. Multivariate analysis showed that distant organ metastasis was significantly correlated with surgery. In stage IV cases, chemotherapy and the number of stage IV factors were independent prognostic factors. In surgery cases, venous invasion, chemotherapy, and residual tumor were independent prognostic factors. R0 was significantly higher in the surgery with chemotherapy group than in the chemotherapy alone group, but there was no significant difference in R1 or R2 cases between the surgery with chemotherapy group and the chemotherapy alone group. In R2 cases, use of a new drug was an independent prognostic factor. The rate of R0 was significantly higher in the preoperative chemotherapy group than in the surgery alone group. In preoperative chemotherapy cases, the S-1/cisplatin (CDDP) group had a 50% 2-year survival rate, and these cases underwent postoperative chemotherapy using the S-1 regimen. A multimodal treatment is considered most effective for stage IV gastric cancer, where this includes preoperative chemotherapy, surgery, and postoperative chemotherapy using the new anti-cancer drugs.