PURPOSE: The surgical resection has been still the only curative treatment modality for the gastric cancer, but the overall prognosis has not been so satisfactory because of high relapse rate. So the necessity of adjuvant chemotherapy has been increased. We evaluated the effect of MLF (5-fluorouracil, leucovorin and mitomycin C) regimen on the prevention of relapse and survival benefit after postopertive adjuvant chemotherapy. MATERIALS AND METHOD: The MLF regimen consisted of 5-FU 375 mg/m2 IV on days 1 through 5; LV 20 mg/m2 IV just before 5-FU infusion on days 1 through 5; and MMC 9 mg/m2 IV on day 1 (7 mg/m2 from the 2nd cycle). RESULTS: One hundred patients were entered into the trial; 56 were male & 44 female, and the range of age was 20 to 82. The total number of chemotherapy cycles was 514. According to AJCC staging, 4 cases were in stage IA, 14 IB, 23 II, 42 IIIA, 15 IIIB, respectively and 2 cases were in stage IV. The estimated median survival was 32 months in stage IIIA, and 28 months in IIIB. The 5 year survival was 90% in stage IB, 76% in II, 29.6% in IIIA and 21.8% in IIIB. Severe neutropenia (WHO grade > or = 3) was observed in 11.8%, and throbocytopenia 0.4%. Severe nausea and vomiting was observed in 1.8%, diarrhea in 1.7%, and mucositis in 1.5%, but there was no toxic death. CONCLUSION: The MLF adjuvant chemotherapy may be effective for resectable gastric cancer with minimal toxicities, but phase III study is needed to confirm its efficacy.
Chemotherapy, Adjuvant* ; Diarrhea ; Drug Therapy ; Female ; Fluorouracil* ; Humans ; Leucovorin* ; Male ; Mitomycin* ; Mucositis ; Nausea ; Neutropenia ; Prognosis ; Recurrence ; Stomach Neoplasms* ; Vomiting

No abstract available
Fluorouracil* ; Lovastatin* ; Stomach Neoplasms* ; Stomach* ; Thymidylate Synthase

PURPOSE: We have conducted this study to investigate the role of c-myc and AAT in gastric carcinoma progression and to see if clinical application of its expression in cancer tissue is of help for the diagnosis or in determining prognosis of gastric carcinoma. MATERIALS AND METHOD: The expression of c-Myc and AAT by immunohistochemical method applied to paraffin-embedded tissue sections of endoscopic biopsy materials of 71 cases of gastric carcinoma (24 early and 47 advanced) and immunoreactivities of antigens were correlated with histological differentiation of carcinoma, degree of tumor infiltration of mononuclear cells, serum levels of carcinoembryonic antigen (CEA) and presence of distant metastases. RESULTS: c-Myc in gastric carcinoma tissue was expressed in 24 cases (33.8%), and the rate of immunoreactivity of c-Myc was higher in the advanced carcinoma cases (38.2%) than early carcinoma cases (25.0%), but the difference was not stastistically significant. The elevated c-Myc expression correlated well with the elevation of serum CEA levels (P<0.05), with the presence of distant metastses (p<0.05), especially with peritoneal metastsis (p<0.05). AAT expression in gastric carcinoma was shown in 11 cases (14.1%), and the rate of immunoreactivity of AAT was significantly higher in advanced carcinoma cases (21.3%) than early carcinoma cases (4.2%) (p<0.05). The elevated expression of AAT correlated well with the elevation of serum CEA levels (p<0.05), and showed negative correlation with the degree of mononuclear cell infiltration in tumor area (p<0.05). The increased expression of c-Myc and AAT in gastric carcinoma correlated well (p=0.05, k= 0.31), which suggests the cooperative action of the two in gastric carcinoma progression. CONCLUSIONS: Our findings suggest that c-Myc expression may be a good marker of high grade malignancy in gastric carcinoma, and may be able to be used clinically in predicting distant metastases, especially for peritoneal dissemination. Our data also imply that c-myc, through its proliferative action, may play an important role in the progression of gastric carcinoma in cooperation with AAT which has immunosuppresive action.
Biopsy ; Carcinoembryonic Antigen ; Diagnosis ; Neoplasm Metastasis ; Prognosis

PURPOSE: We measured the gastric cancer tissue uPA and plasminogen activator inhibitor-1 (PAI-1) levels and compared them to those of the peripheral and portal blood levels to evaluate the correlation. MATERIALS AND METHODS: Tissue uPA and PAI-1 levels were measured by ELISA assay (Monozyme, Netherland) in paired 85 normal and cancer tissues resected from gastric cancer patients. In 50 patients, blood uPA and PAI-1 levels were measured from pre- operative peripheral and portal blood, post-operative portal blood. RESULTS: Gastric cancer tissue uPA and PAI-1 levels increased from the early stage. The elevated cancer-to-normal ratios of the uPA and PAI-1 were constant from stage I to IV. There were correlations of uPA between normal and cancer tissues (r2=0.38) and between peripheral and pre-resection portal blood level (r2=0.64). There were no correlations between tissue PAI-1 level and blood PAI-1 levels. However, there were correlations in PAI- 1/uPA ratio between cancer tissue and peripheral blood (r2=0.25), peripheral blood and pre- resection portal blood (r2=0.60). CONCLUSION: Even if the cancer tissue levels of uPA and PAI-1 increased from the early stage of gastric cancer, only blood uPA level correlated with tissue uPA level. A modest correlation found in PAI-1/uPA ratio between cancer tissue and blood suggests applicability of blood PAI-1/uPA ratio in predicting tissue uPA, PAI-1 expression.
Enzyme-Linked Immunosorbent Assay ; Humans ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Stomach Neoplasms* ; Urokinase-Type Plasminogen Activator*

PURPOSE: The development of new therapeutic modalities such as gene therapy, which still requires further investigation, is clearly important to improve the prognosis of gastric cancer. This study was conducted to evaluate the effect on the growth and the tumorigenicity of retrovirus-mediated p53 gene transduction into gastric cancer cells. MATERIALS AND METHODS: Human gastric cancer cell lines were cultured and their DNAs were analyzed to evaluate the p53 status with PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and DNA sequencing. Retroviral supernatants were obtained from each producer cell line, PA317/LNCX and PA317/LNC/p53, after construction of retroviral vector LNC/p53 containing human p53 cDNA and producer cell line PA 317/ LNC/p53. To investigate the effect of retrovirus-mediated p53 gene transduction in human gastric cancer cell lines, the in vitro growth rates and in vivo tumorigenicities of the N-87 cell line having mutant p53 and the YCC-S-2 cell line having wild-type p53 were compared before and after infection with LNC/p53 retrovirus. RESULTS: The following results were obtained: 1) The growth inhibition of N-87 cells after p53 transduction was signficant when compared to that of the parent N-87 cells. The growth of the p53 transduced YCC-S-2 cells and the parent YCC-S-2 cells was not different. 2) In nude mice, the growth of tumors formed by N-87 cells was modestly inhibited after retrovirus-mediated wild-type p53 gene transduction. However, the growth of tumors formed by YCC-S-2 cells was not inhibited by retrovirus-mediated p53 gene transduction. 3) The expression rate of p53 protein after p53-containing retroviral infection in the KATO-III cell lines, which have no p53 gene, was dose-dependent on the m.o.i. of retrovirus, although it was not more than 15% with the m.o.i. of 100 upon immunohistochemical analysis. CONCLUSION: The growth inhibition by retrovirus-mediated p53 transduction in human gastric cancer cells was significant in a gastric cancer cell line having mutant p53 in vitro, and the growth of tumor masses formed by a gastric cancer cell line having mutant p53 was modestly inhibited after p53 transduction using retroviral vector in nude mice, although it was not statistically significant. Only modest inhibition of tumor growth using retrovirus-mediated p53 gene transduction in vivo is most likely to be due to low transduction efficiency.
Animals ; Cell Line* ; DNA ; DNA, Complementary ; Genes, p53* ; Genetic Therapy ; Humans* ; Mice ; Mice, Nude ; Parents ; Prognosis ; Retroviridae ; Sequence Analysis, DNA ; Stomach Neoplasms* ; Zidovudine

PURPOSE: Reclassfication of the medullary carcinoma using a strict histologic criteria and analysis of the clinical and pathological characteristics of the medullary carcinoma. MATERIAL & METHODS: Thirty-seven cases of the breast carcinoma originally diagnosed as medullary carcinoma were reviewed. One to ten microscopic slides of each case were reexamined and reclassified using the strictly defined histologic criteria defined by Ridolfi et al. Tumors were excluded from the category of the typical medullary carcinoma (TMC) on the basis of presence of glandular features, focal marginal infiltrations, or sparse mononuclear infiltrations. Tumor with two or more atypical features, or extensive marginal infiltrations, no mononuclear cell infiltration and/or less than 75% syncytial growth were classified as infiltrating ductal carcinoma with medullary feature (IDC). A predominantly syncytial growth pattern (75% or more) was requisite for inclusion in both TMC and atypical medullary carcinomas (AMC). RESULTS: Twenty-two tumors (60%) fulfilled the criteria for TMC, and 12 tumors (32%) were AMC and three tumors (8%) were IDC. TMC occupied 3.1% of breast cancer. The mean age of patients with TMC was 45.4+/-11.2 years and the average size of the tumor in TMC was slightly larger than that of breast cancer in general, although not statistically significant. The frequency of lymph node metastasis in TMC was similar to breast cancer in general. Five year survival of patients with TMC was 95.5% which was significantly better than breast cancer in general. CONCLUSION: The TMC occupied 3.1% of breast cancer. The mean age of patient, tumor size and lymphnode metastasis were not different from that of breast cancer but 5 years survival of patient with TMC was significantly better than breast cancer in general.
Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Carcinoma, Medullary* ; Humans ; Lymph Nodes ; Neoplasm Metastasis

PURPOSE: To evaluate the relationship between nuclear DNA contents and prognostic factors and survival in breast cancer patients. MATERIALS AND METHODS: We determined nuclear DNA content from 91 paraffin-embedded malignant breast tumors and evaluated relationship between DNA nuclear content and well-known prognostic indicators of breast cancer and the survival of the patients by statistical analyses. RESULTS: Twenty nine (34.5%) of the 91 tumors examined were diploid, and the remainder (65.5%) contained one or more aneuploid clones. S-phase fraction (SPF) ranged from 1.4 to 68.3% (median 11.2%) and it was higher in aneuploidy tumors than in diploid tumors (p<0.05). Positive axillary lymph nodes were found in 72.7% of the patients who had a tumor with a high SPF (above the median 11.2%) and in 27.3% of those with tumor with low SPF (below median) (p<0.05). The overall survival rate was 96.1% in DNA diploid and 87.6% in DNA aneuploid tumors, showing that DNA ploidy had no prognostic significance in breast cancers. The actuarial survival rates were 96.4% and 86.3% for low and high SPF, respectively (p=0.28). The patients with high SPF showed high disease free survival rate compared to the patients with low SPF but the difference had no statistical significance. CONCLUSION: Our results indicate DNA aneuploid tumors were more prevalent in breast cancer patients with high SPF or lymph node metastasis and larger patient accumulation with longer follow-up period will be helpful to identifiy the relationship between flow- cytometrical analysis and prognosis.
Aneuploidy ; Breast Neoplasms* ; Breast* ; Clone Cells ; Diploidy ; Disease-Free Survival ; DNA* ; Follow-Up Studies ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Ploidies ; Prognosis ; Survival Rate

PURPOSE: Oncogen or growth factor receptor such as phospholipase C isoenzyme gamma-1 (PLC gamma-1), epidermal growth factor receptor (EGFR), and Her-2/neu which related with tyrosin kinasemay and then regulating vell proliferation may have a role as prognostic factors for breast cancer. MATERIAL AND METHODS: With assumption that expression of PLC gamma-1, EGFR and Her-2/neu oncogene has close relationship with prognosis of breast cancer, 59 breast cancer patients who were operated upon at Korea University Hospital during a period of 6 years starting June 1988 to May 1994 were selected for this study. This study was carried out by comparing between expression of PLC gamma-1, EGFR and Her-2/neu oncogene and patient's survival rate. These expression were also compared with TNM system, estrogen and progesterone receptor and at same time these expressions were compared with each other to see whether there are any relationship among these expression. RESULTS: Expression of PLC gamma-1, EGFR and Her-2/neu were present in 42% (25/59), 46% (27/59) and 20% (12/59). The expression of PLC gamma-1 was closely related with the expression of EGFR (p<0.05) and Her-2/neu (p<0.05), but there were no relationship between the expression of PLC gamma-1 and hormonal receptors and TNM stage (p>0.05). The expression of EGFR was closely related with the expression of Her-2/neu (p<0.05) and hormone receptors (p<0.05), but there were no relationship between the expression of EGFR and pathologic TNM stage (p>0.05). The expression of Her-2/neu was not closely related with hormone receptors and TNM stage except axillary lymph node metastasis. There were close relationship between overall and disease free survival and PLC gamma-1 and Her-2/neu. But EGFR had only related with disease free survival rate. CONCLUSION: In conclusion, the expression of PLC gamma-1, EGFR and Her-2/neu oncogene in human breast cancer may be useful prognostic factors independently and it may potentiated its individual value as a prognostic factors if use them together.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Epidermal Growth Factor* ; Estrogens ; Humans* ; Korea ; Lymph Nodes ; Neoplasm Metastasis ; Oncogenes ; Phospholipases* ; Prognosis ; Receptor, Epidermal Growth Factor* ; Receptors, Progesterone ; Survival Rate ; Type C Phospholipases*

PURPOSE: To understand the involvement of BRCA1 gene in Korean breast and/or ovarian cancer families. MATERIALS AND METHODS: Germline mutations of BRCA1 gene were analyzed in 13 families which included 3 hereditary site-specific breast cancer families, 6 suspected breast cancer families, and 3 suspected breast-ovarian cancer family, and one Li-Fraumeni family by screening BRCA1 gene using single strand conformation polymorphism (SSCP) analysis on polymerase chain reaction (PCR) amplified genomic DNA and confirmed the results by sequencing. RESULTS: Including one family with previously reported nonsense mutation of BRCA1 gene, we detected two mutations in unrelated families. One newly identified mutation was frame shift mutation resulting from TG deletion in codon 1701, which results in a truncated BRCA1 protein, at codon 1714. CONCLUSION: The proportion of families who inherit the mutated BRCA1 gene seems to be small among Korean breast and/or ovarian cancer families.
BRCA1 Protein ; Breast Neoplasms ; Breast* ; Codon ; Codon, Nonsense ; DNA ; Frameshift Mutation ; Genes, BRCA1* ; Germ-Line Mutation* ; Humans ; Mass Screening ; Ovarian Neoplasms* ; Polymerase Chain Reaction

PURPOSE: Prognosis of primary gastric cancer invading neighboring organs is very poor. However, with en bloc resection, a relatively favorable prognosis can be expected even in patients with such advanced cancer. But there has been controversy on the effectiveness of gastrectomy combined with en bloc resection of the invaded organs, and we conducted this study to evaluate the prognostic effects as well as the outcome of the combined resection. MATERIALS AND METHODS: Among 2,603 who underwent gastrectomy due to gastric carcinoma from January 1987 to December 1994 at the Department of Surgery, Yonsei University College of Medicine, 157 patients (6.0%) in whom curative combined resections of grossly invaded adjacent organs (cT4) were perfonned entered this study. Any case with distant metastasis was excluded. Comparisons and multivariate analysis between the invasion (pT3) group and the non-invasion (pT4) group were made for age, sex, tumor size, location, Borrmann type, depth of invasion, lymph node metastasis, histologic type and 5-year survival rate. RESULTS: One-organ combined resection was done in 60 (38.2%) patients; Two-organ, in 80 (51.0%) patients; and three-organ, in 17 (10.8%) patients. Most commonly combined organ was distal pancreas and transverse colon was the next. Histologic confirmation of invasion was made in 40.9%. 157 patients with T4 were divided into pT3 or pT4. Significant differences were found in type of operation, location of tumor, and TNM staging. Postoperative complications of combined resection were observed in 48 cases (30.6%) and the wound infection was the most frequent one. There were only 2 cases (1.3%) of immediate postoperative mortality in the combined group, and the causes of death were pulmonary complication and acute renal failure. Five-year survival rate (5-YSR) of pT3 group was 43.0% and that of pT4 was 26.2%. In comparison of 5-YSR according to TNM stages, no significant difference was found between pT3 and pT4 (45.0% vs. 66.7% in IIIa; 25.4% vs. 18.4% in IV). No difference of 5-YSR was observed in the groups categorized according to the number of resected organs. The comparison of 5-YSR between the 157 curatively-combined cases and the 63 palliatively-combined cases showed a significant difference (35.6% vs. 4.2%, p=0.000). Multivariate analysis showed that lymph node metastasis and microscopic tumor invasion served as significant parametets. CONCLUSION: En bloc combined resection of adjacent invaded organs along with systematic lymph node dissection would be beneficial to gastric cancer patients with neighboring organ invasion.
Acute Kidney Injury ; Cause of Death ; Colon, Transverse ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Mortality ; Multivariate Analysis ; Neoplasm Metastasis ; Neoplasm Staging ; Pancreas ; Postoperative Complications ; Prognosis ; Stomach Neoplasms* ; Survival Rate ; Wound Infection