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Yasuo Koyama

Publications and source records attributed to Yasuo Koyama.

6 recordsLinked to original sources
PubMed2005

A multicenter randomized study comparing 5-fluorouracil continuous infusion (ci) plus 1-hexylcarbamoyl-5-fluorouracil and 5-FU ci alone in colorectal cancer.

To verify the effectiveness of oral 1-hexylcarbamoyl-5-fluorouracil (HCFU) in improving the surgical cure rate in advanced colorectal cancer, a multicenter randomized comparative study was conducted. A total of 429 patients who had had curative resection for stage II and III colorectal cancer were randomly assigned to a study group receiving a 14-day course of 5-FU continuous infusion (320 mg/m2/day) followed by oral HCFU for a year (300 mg/day), or to the control group receiving a 14-day course of 5-FU continuous infusion alone. In terms of background factors, no significant differences were found between the 214 patients in the study group and the 215 in the control group. Adverse reactions during the treatment were more frequently seen in the study group. But with few exceptions, the toxicities were mild and the compliance was acceptable. The 5-year overall survival rate of the study group was similar to that of the control group. The 5-year disease-free survival rate of the study group was better than that of the control group in the patients with colon cancer (hazard ratio=1.87; 95% confidence interval 1.03-3.38; p=0.037). However, this benefit was not seen in the patients with rectal cancer. A significant improvement in the disease-free survival rate was demonstrated through the addition of HCFU to 5-FU continuous infusion for the patients with colon cancer. The usefulness of oral fluoropyrimidine as an adjuvant for curative surgery for colon cancer was further warranted.

Adult↗
PubMed2003

Methylation profile of the MLH1 promoter region and their relationship to colorectal carcinogenesis.

Methylation of the MLH1 promoter region has been suggested to be a principal mechanism of gene inactivation in sporadic microsatellite instability (MSI)-positive colorectal carcinoma. Recently, we have shown a novel methylation profile of the MLH1 promoter region (i.e., full, partial, and no methylation), among which full methylation was strongly associated with MSI. In this study, to confirm whether methylation requires the involvement of both alleles, we studied the MLH1 promoter region concerning the methylation profile and allelic loss. Furthermore, we studied correlations of methylation profiles with genetic alternations such as loss of heterozygosity (LOH) of the TP53 locus and KRAS mutation. Eighty-eight tumors were classified as full (n = 14), partial (n = 26), and no methylation (n = 48). Full methylation was observed in 78% (14/18) of high-frequency MSI, in which all CpG sites in the promoter region were methylated. Full methylation differed significantly from partial methylation regarding absence of TP53 LOH (0/12) and KRAS mutation (0/14). In cases with full methylation, we could show biallelic methylation by use of a single-base nucleotide polymorphism in the promoter. However, this did not accompany LOH of the MLH1 locus. In contrast, there were no significant differences in molecular features between partial and no methylation, except for low frequencies of LOH of the MLH1 locus (P = 0.02). In conclusion, biallelic extensive methylation of the MLH1 promoter region plays a significant role in gene inactivation and is independent of KRAS mutation and TP53 LOH.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Changes in colorectal cancer during a 20-year period: an extended report from the multi-institutional registry of large bowel cancer, Japan.

PURPOSE: This study was designed to examine trends of colorectal cancer in relation to age, gender, site, and survival during the past 20 years. METHODS: The multi-institutional registry of the Japanese Society for Cancer of the Colon and Rectum offered 87,695 surgical cases with invasive adenocarcinoma during 1978 to 1997 for analysis. We calculated survival rates and used the Cox's proportional hazard model for cases during 1978 to 1994. RESULTS: The number of cases showed a 2.5-fold increase with consistent male predominance confined to the distal colon and the rectum. Colon cancer in the last five-year period was more likely right-sided for females (odds ratio, 1.26; 95 percent confidence interval, 1.16-1.38) and males (odds ratio, 1.16; 95 percent confidence interval, 1.06-1.25) compared with the first period. Cancers in younger patients were more likely at Stage III to IV in the late 1990s if the cancers were in the distal colon, the rectum (for both genders), or the proximal colon (for females). Survival was improved except for cases with proximal colon cancer of Stage IV. In the multivariate analysis, hazard ratios for death in the postoperative five years were 0.77, 0.59, and 0.66 for proximal colon, distal colon, and rectal cancers, respectively, in the last period as compared with those in the first period [corrected]. Reduced hazard ratio for females was the largest for proximal colon cancer with Stage I to II. CONCLUSION: Although surgical outcome was largely improved, delayed presentation or diagnosis in younger patients remained a problem. Preferential localization in the proximal colon and survival benefit for females should be investigated.

Adenocarcinoma↗
PubMed2002

Changing site distribution of colorectal cancer in Japan.

PURPOSE: In North America and other high-risk areas, there has been a proximal shift in the subsite distribution of colorectal cancer. We wanted to determine whether any similar change has occurred in Japan, and where the incidence of this disease has increased sharply. METHODS: Data from the Reports of the Japanese Society for Cancer of the Colon and Rectum were used to analyze the time trend of colorectal cancer in Japan between 1974 and 1994 according to the patients' age at diagnosis and sex, and the site of the tumor within the colon or rectum. RESULTS: The percentage of patients over the age of 70, especially females, increased. The increase in the percentage of right-sided colon cancer in colorectal cancer cases was accompanied by a continuous decline in the percentage of rectal cancer in both sexes at all ages. In general, the percentage of right-sided colon cancer in colon cancer cases was stable in men, but increased in women. The rate among patients older than 70 years increased in men, but predominated and remained stable in women. No proximal shift in colon cancer was found in either sex under the age of 69. CONCLUSION: These findings indicated that a proximal shift in the subsite distribution of colorectal cancer has occurred in Japan. This rightward shift of colorectal cancer is due to the decreasing proportion of rectal cancer. Furthermore, the increasing proportion of older patients, especially females, may be another major determinant of the changing colon cancer subsite distribution.

Aged↗
PubMed2002

[Neo-adjuvant chemotherapy with carmofur for colorectal cancer--a multi-institutional randomized controlled study].

The efficacy and safety of preoperative chemotherapy with carmofur (HCFU) for colorectal cancer were evaluated in a randomized controlled study involving 63 institutes in the Kanto area. Patients aged 75 or younger with Dukes' B or C colorectal cancer were eligible if curative surgery was expected. In the end, 326 were eligible from 405 consecutive colorectal cancer patients. Patients in both the control (n = 162) and the new treatment group (n = 164) were given intravenous mitomycin C (MMC) 6 mg/m2 on day 0 and 7 after surgery and HCFU 300 mg/day orally from day 14 for a year. Patients in the new treatment group were also given oral HCFU for 14 days or more prior to surgery. All 326 patients were followed for 5 years or longer. Five-year overall and disease-free survival rates were not significantly different between the two groups (75.4% and 71.6% for the control, and 71.8% and 71.5% for the study group, respectively). In the subset analysis, neither cancer site nor nodal status affected the differences in overall- and disease-free survival rates between the groups. The present findings show no additional efficacy of preoperative chemotherapy with HCFU in survival from advanced colorectal cancer. Further investigations in terms of patient selection, treatment regimen, combined use of radiotherapy, and other factors would be required to determine the significance of preoperative chemotherapy against advanced colorectal cancer.

Aged↗