No abstract

Recent molecular studies have shown that the genetic profiles of differentiated-type adenocarcinomas of the stomach are associated with distinct cellular mucin phenotypes (gastric-intestinal-and mixed-phenotypes). Therefore, we examined whether these cellular mucin phenotypes reflect specific molecular genetic alterations, and whether the phenotypes can be used to help categorize the intramucosal neoplasias of gastric tumors. We subclassified tumors into four cellular phenotypes using immunohistochemical mucin analysis. In all, 62 early gastric carcinomas (gastric-phenotype, 13; intestinal-phenotype, 17; mixed-phenotype, 31; unclassifiedphenotype, 1) were examined using a combination of polymerase chain reaction microsatellite assays and immunohistochemical analysis in order to detect chromosomal allelic losses of multiple cancer-related chromosomal loci (1p, 3p, 4p, 5q, 8p, 9p, 13p, 17p, 18q and 22q), microsatellite instability (MSI), and overexpression of the p53 protein. In addition, we analyzed the relationship between MSI status and hMLH1 promoter hypermethylation, which is thought to be a cause of high MSI status. For gastric phenotype cancers, the frequency of 3p allelic loss was higher than that of other microsatellite markers, whereas 5q allelic loss was frequently found in intestinal phenotype cancers. The genetic profile of mixed phenotype cancers is comprised of two distinct genetic types: LOH and MSI types. In the former, 5q, 3p and 18q allelic losses are seen frequently in intramucosal carcinomas. On the other hand, 17p, 1p and 9p allelic losses are associated with the development of submucosal carcinomas. MSI was observed only in mixed phenotype cancers (six of 31 mixed phenotype cancers). Overexpression of the p53 protein is common in differentiated-type gastric cancers. In addition, the MSI status of the tumor cells was correlated with the extent of hypermethylation of the hMLH1 promoter. We suggest that the cellular mucin phenotypes of the differentiated-type adenocarcinomas result from distinct genetic alterations.

No abstract

BACKGROUND: Lymph node metastasis in patients with gastric cancer is one of the important prognostic factors. However, there is no consensus concerning the best classification for lymph node metastasis as a prognostic factor. So, to evaluate the ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (the ratio of LN meta) as a prognostic factor, we compared the ratio of LN meta with lymph node status according to the Japan Classification of Gastric Carcinoma and the total number of metastatic lymph nodes with multivariate analysis.METHODS: Between 1991 and 1997, a total of 360 patients with primary gastric cancer who underwent gastrectomy with D2 or more extended lymph node dissection were included in this study. Ten kinds of prognostic factors and three types of different classifications for lymph node metastasis were analyzed by multivariate analysis using the Cox regression.RESULTS: The average number of dissected lymph nodes and metastatic lymph nodes were 55.0 (range, 11-184) and 2.6 (range, 0-86), respectively. There were significant differences of the 5-year cumulative survival rates among each group of the ratio of LN meta (0%, 1%-9%, 10%-24%, and more than 25%). Age, tumor size, curability, and the ratio of LN meta were selected as independent prognostic factors by forward stepwise selection. The ratio of LN meta showed the highest hazard ratio by Cox regression.CONCLUSION: The ratio of LN meta appears to be an important prognostic factor and the best classification factor for lymph node metastasis.

No abstract

No abstract

Summary We attempted to characterize the motivation, comprehension and expectations of patients who had given informed consent to participate in phase I trials of anti-cancer agents at the National Cancer Center of Japan. Thirty-three patients were given a simple multiplechoice questionnaire and asked to return it at a later date. The completed survey was returned by 32 patients. The patients were surveyed before they had received any investigational phase agents. Nineteen per cent of patients were motivated to participate in the phase trials by the possibility of therapeutic benefit, 9% because participation seemed a better choice than no treatment and only 6% for altruistic reasons. Most patients comprehended the major features of a phase trial, namely its investigational nature, the unknown effects of the agent investigated and the unclear benefit to the patients themselves. Fifty-nine per cent of the patients anticipated that they might suffer severe or life-threatening side-effects if they participated in the phase trial, and 43% were able to indicate accurately the purpose of the phase trial as a dose determination study. Although only a minority of the patients indicated that their motivation to participate was possible treatment benefit to themselves, when answering questions regarding expectations, more than half indicated that there might be personal benefits of varying degrees by participation.

No abstract