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Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 199 records · Page 11Linked to original sources

[Cooperative Study of Surgical Adjuvant Chemotherapy for Colorectal Cancer (fourth report): five-year results after surgery].

In collaboration with 428 institutions nation-wide, comparative studies on the optimal daily dosage of UFT were carried out for non-curative resection cases of colorectal cancer for two years from January 1984 to December 1985. The administration method employed was as follows. Group C received 12 mg/m2 of MMC on the day of operation, followed by 6 mg/m2 every 2 months 6 times, and from the 2nd week after the operation 600 mg/body of UFT was continuously administered every day for 1 year. Group D received 400 mg/body of UFT every day and the same amount of MMC as Group C. Analysis was made of 556 evaluable cases. There was no difference in the survival rate between the two groups. With respect to the dosage per body weight (kg), 8-12 mg/kg of UFT produced good prognoses and less side effects than the group which received more than 12 mg/kg. It seems necessary to administer UFT at its optimal dosage for colorectal cancers.

Antineoplastic Combined Chemotherapy Protocols↗

[Experimental and clinical study in vitro chemosensitivity test for succinate dehydrogenase inhibition test].

The usefulness and problems in the succinate dehydrogenase inhibition (SDI) test as an in vivo chemosensitivity test were reviewed and discussed. SDI test is based on the correlation of succinate dehydrogenase activity with cell viability. The optimal condition of SDI test were evaluated with respect to concentration of anticancer drugs, incubation time, effect of sodium succinate on formazan production and enzymatic disaggregation of solid tumors. Analysis of the chemosensitivity of clinical tumors revealed that the origin of tumor, histological differentiation, DNA distribution patterns, estrogen receptor status in breast cancer, and difference of primary and metastatic lesions were critical for determining the chemosensitivity of tumor tissues. Correlation between in vitro sensitivity in the SDI test and in vivo clinical results of chemotherapy was evaluated. Since SDI test reflects cell viability and is a simple, rapid and inexpensive methods, it is appropriate both for clinical chemosensitivity testing and for the screening of anticancer drugs.

Colonic Neoplasms↗

[Fluorocytometric DNA analysis of intestinal metaplasia associated with gastric carcinoma].

Histopathologic studies and fluorocytometric DNA analysis were carried out in 39 patients with intestinal metaplasia (IM) of the mucosa associated with gastric carcinoma, in order to determine possible relationships. According to the histological degree of IM, 39 cases were divided into 16 (41%) with slight-to-moderate, and 23 (59%) with severe IM. The 39 tumors were histologically divided into 20 (51%) differentiated tumors and 19 (49%) undifferentiated tumors. The DNA patterns of tumors revealed 17 (43%) to be euploidy and 22 (57%) to be aneuploidy. The DNA content of the metaplastic epithelial cells was measured, and the percentage of the cells in S and G2 + M phases of the cell cycle was taken as the index of proliferative activity. DNA analysis of the non-metaplastic epithelium was performed in 10 as a control group. While the histological differentiation of the tumors and the degree of IM were not related to the proliferative activity of IM, the IM around the aneuploid tumors did have higher proliferative activity (14.01 +/- 6.16%) than that around euploid tumors (11.08 +/- 7.13%) or of normal mucosa (9.95 +/- 9.92%). This approach will help to determine cell kinetics of IM around the gastric tumor. Our study indicated a relationship between DNA ploidy and the proliferative activity of IM around gastric cancer.

Cell Cycle↗

Poorly differentiated medullary carcinoma of the stomach.

BACKGROUND: The biologic behavior of poorly differentiated medullary carcinoma of the stomach is unclear. METHODS: A clinicopathologic study on 74 poorly differentiated medullary carcinomas (PMC) and 73 nonmedullary carcinomas (NMC) of the stomach was done. PMC were defined as gastric carcinomas in which more than 50% of the tumor area contained poorly differentiated adenocarcinoma with no fibrous stroma. RESULTS: They were characterized by a location in the upper 33% of the stomach (49%), grossly expansive growth (69%), frequent vascular permeation (57%), and simultaneous liver metastasis (15%). Although the 5-year survival rate was similar for PMC and NMC, death of PMC was related more frequently to liver metastasis (47%) and less frequently to peritoneal dissemination (12%). The outcome of patients with PMC was influenced by frequent vascular permeation, extended lymph node metastasis, and simultaneous liver metastasis. CONCLUSIONS: These results indicate that PMC are characterized by expansive growth of the tumor and simultaneous or recurrent metastasis to the liver. Therefore, the biologic behavior of poorly differentiated medullary carcinoma is similar to that of well-differentiated carcinoma of the stomach.

Carcinoma↗

Hyperthermia enhances the inhibition of tumor growth by 1-(2-tetrahydrofuryl)-5-fluorouracil/uracil (1:4) in tumors in mice and humans.

The cytotoxicity of several antitumor drugs is enhanced by hyperthermia (HT). Using mouse Sarcoma-180 (S-180) tumors, the authors examined the effects of 5-fluorouracil (5-FU) and a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and uracil in a molar ratio of 1:4 (UFT), in combination with HT. The antitumor effect of 5-FU was not enhanced significantly by HT. Growth inhibition by UFT plus HT was significantly greater than that by UFT alone, whereas inhibition by UFT alone was significantly greater than that by 5-FU. The intracellular metabolism of 5-FU and FT in whole homogenates of S-180 cells, human tumor cell lines (SC-2 and Lu-99), and five fresh human tumor tissues also was investigated. Conversion of FT to 5-FU, phosphorylation, and degradation of 5-FU were assayed with [3H]FT or [3H]5-FU, and the products were separated by thin-layer chromatography. The conversion of FT to 5-FU and the phosphorylation of 5-FU were more rapid at 43 degrees C than at 37 degrees C, whereas the degradation of 5-FU to 2-fluoro-beta-alanine remained unchanged. This acceleration of the active metabolism of FT and 5-FU may be one explanation for the enhanced effect of UFT by HT.

Animals↗

Prophylactic lymph node dissection in patients with advanced gastric cancer promotes increased survival time.

BACKGROUND: There is no consensus of opinion regarding the efficacy of lymph node dissection. METHODS: Data were analyzed from 452 patients with advanced gastric cancer who underwent curative resection in the Department of Surgery II, Kyushu University Hospital, between 1970 and 1985, with special reference to the lymph node metastasis. RESULTS: Metastatic lesions were evident in the dissected lymph nodes of 300 of 452 (66.4%) patients. Survival time for patients without lymph node metastasis was longer than for those with it (P less than 0.01). In patients without lymph node metastasis, the tumor was smaller, serosal invasion was less prominent, tumor growth was less infiltrating, and the tumor stage was, therefore, less advanced. Lymphatic involvement was found in 38.9% of the patients with no evidence of lymph node metastasis. CONCLUSIONS: Because the postoperative mortality rate is low in patients with lymph node dissection, the authors advocate prophylactic lymph node dissection to prevent a recurrence.

Aged↗

Flavone acetic acid increases the antitumor effect of hyperthermia in mice.

The combined effects of flavone acetic acid (FAA), a synthetic flavonoid, and hyperthermia on B16 melanoma cells were investigated. In vitro, FAA alone at concentrations below 100 micrograms/ml was not cytotoxic with a 60-min exposure at 37 degrees C. Hyperthermia at 43 degrees C for 60 min enhanced the cytotoxicity of FAA only at concentrations over 100 micrograms/ml. Inhibition of the growth of B16 melanoma solid tumor by FAA and/or hyperthermia was examined in vivo. FAA (100-200 mg/kg) inhibited tumor growth in a dose-dependent manner. The combined treatment of FAA (200 mg/kg) and hyperthermia (43 degrees C, 15 min) significantly inhibited tumor growth compared to a treatment of FAA or hyperthermia alone. The maximum antitumor effect of FAA combined with hperthermia was obtained when FAA was administered 2 or 4 h before heat. The significantly increased cytotoxicity of FAA combined with hyperthermia seems to relate to specific decreases in tumor blood flow, a reduction in tumor pH, and an increased tumor temperature, without altering pH in the normal tissues. This combined treatment of FAA and hyperthermia warrants further study for treating subjects with solid tumors.

Animals↗

Signet ring cell carcinoma of the stomach.

Between 1965 and 1985, 51 of 1500 patients (3.4%) with gastric cancer who had gastric resection had signet ring cell gastric cancer. Patients with this form of cancer tended to be younger and female; the tumors were smaller and involved the stomach body, serosal invasion was less prominent, and lymph node metastases were less likely to be present. Early mucosal and submucosal cancer was present in 54.9% of the patients with the signet ring cell and in 24.6% with other types of gastric cancer. In 15.7% of patients with signet ring cell cancer, a noncurative resection was performed. The 5-year survival rate was 74.5% for patients with signet ring cell cancer and 52.4% for those with other types of gastric cancer (P less than 0.01). In patients with signet ring cell gastric cancer, the lesion is less extensive; thus, these patients probably can expect a longer survival time.

Adenocarcinoma, Mucinous↗

A clinicopathologic study of mucinous gastric carcinoma.

A clinicopathologic study of 42 mucinous gastric carcinomas (MGC) and 73 nonmucinous gastric carcinomas (NGC) was done. The tumor was defined as MGC when more than one half of tumor area had mucin pools. The 5-year survival rate for curatively treated patients was almost the same in MGC (58%) and NGC (56%), and clinicopathologic features, except for lymphatic permeation, showed no significant difference between MGC and NGC. Findings in MGC patients who died of a recurrence within 3 years included total gastrectomy, upper location, large size, infiltrative growth, extraserosal invasion, positive lymph node metastasis, more advanced stage, and a noncurative operation. There was no significant correlation between the degree of mucin content and other data, including the prognosis. Histologically, MGC were divided into well-differentiated and poorly differentiated types, according to the degree of glandular formation of the tumor cells. In patients with well-differentiated MGC, the age of onset was older, tumor growth was localized, and there were metastases to the liver. In patients with poorly differentiated MGC, the age of onset was younger, tumor growth was infiltrative, and there was peritoneal dissemination. These results show that the biologic behavior of MGC is similar to that of NGC and that the lesion basically is determined by the histologic subtype, not by the mucin content.

Adenocarcinoma↗

Chemosensitivity and DNA ploidy in head and neck squamous cell carcinomas.

The succinate dehydrogenase activity and cellular DNA content of human head and neck squamous cell carcinomas were examined, and the chemosensitivity and ploidy status were compared with histologic differentiation. The average decrease of enzyme activity in the poorly differentiated squamous cell carcinomas was significantly greater than that of well- and moderately differentiated squamous cell carcinomas. Statistically significant differences were also noted with relation to the original site of the primary tumor. The chemosensitivity of a tumor with DNA aneuploidy tended to be lower among the well- and moderately differentiated squamous cell carcinomas and higher among the poorly differentiated type. We conclude from this study that simultaneous analysis of the chemosensitivity and DNA ploidy will aid not only in selecting effective antitumor drugs but also in predicting changes in cellular characteristics during the course of disease.

Antineoplastic Agents↗

Predictors of lymph node metastasis in early gastric cancer.

Data were analysed on 396 patients with early gastric cancer who underwent resection in this department; special reference was made to lymph node metastasis. Metastases were present in the dissected lymph nodes of 47 patients (11.9 per cent). The survival rate for patients with metastasis to lymph nodes was lower than for those without such metastasis (P less than 0.05). Lymph node metastasis was associated with larger tumour, a higher incidence of submucosal invasion, a higher rate of lymphatic vessel involvement, an advanced stage of disease and a non-curative resection rate of 6.4 per cent. Multivariate analysis showed that the independent risk factors for lymph node metastasis in patients with early gastric cancer were large tumour size, lymphatic vessel involvement and invasion into the submucosal layer. In patients with these risk factors, lymph node dissection and postoperative adjuvant therapy should be performed in an attempt to prevent recurrence in the form of lymph node metastasis.

Female↗

Quality of life after gastrectomy in patients with carcinoma of the stomach.

One hundred and fifty patients without recurrence of disease after R2 gastrectomy for carcinoma of the stomach were interviewed to determine their quality of life after surgery. Patients ate less and weighed less but most appeared to be well adjusted and had an optimistic attitude regarding their physical state. There was no evidence of a diminished quality of life in those who had undergone distal partial gastrectomy. These patients had a higher overall food tolerance, body-weight and performance status compared with those treated by total gastrectomy. Considering the satisfactory outcome and the sustained quality of life, radical R2 gastrectomy may be the treatment of choice for carcinoma of the stomach.

Body Weight↗

Primary malignant tumors of the small intestine: analysis of 40 Japanese patients.

Forty Japanese patients with primary malignant tumors of the small intestine were reviewed. Adenocarcinoma was the most common tumor type comprising 19 patients (47%), followed by malignant lymphoma, 11 (30%), leiomyosarcoma, 8 (20%) and carcinoid tumor, 1 (3%). Adenocarcinomas and leiomyosarcomas were primarily located in the duodenum or jejunum, whereas lymphomas were more common in the jejunum or ileum. Abdominal pain (65%) and nausea or vomiting (35%) were the most common symptoms with these tumors. Barium contrast studies were able to detect 83% of these tumors. Our results also suggest that computed tomography and ultrasonography are not reliable for diagnosing jejunal tumors while superior mesenteric angiography is effective for diagnosing ileal tumors. The duodenal and ileal tumors tended to metastasize to lymph nodes while jejunal ones tended to penetrate the serosa or to disseminate into the peritoneal cavity. The percentage of tumors potentially cured by surgery and the 5 year survival rates of the leiomyosarcomas (75% and 57%, respectively) were higher than those of adenocarcinomas (42% and 10%, respectively) and lymphomas (42% and 32%, respectively).

Adenocarcinoma↗

Heterogeneity in gastric carcinoma with special reference to DNA content and mitotic activity: histopathologic differentiation.

DNA ploidy and mitotic activity were microspectrophotometrically investigated in 46 patients with gastric carcinoma. Measurements of DNA content and mitotic index (M.I.) were examined in the mucosal, submucosal, muscularis propria, and serosal layers of tumors, respectively. The frequency of cells with values exceeding hexaploid chromosome (6c) and mitotic counting analysis revealed a significant higher value in serosa, compared with findings in the mucosa. This tendency was not evident in cases of a differentiated type adenocarcinoma but was noted in those with the undifferentiated type. There were 37 tumors (80.0%) with the same DNA distribution patterns in every layer of the stomach (homogeneous DNA ploidy). Heterogeneity of DNA ploidy was observed in nine tumors (20.0%). Carcinoma with a heterogeneous DNA ploidy manifested a significantly higher incidence of metastasis to the lymph nodes than did those with homogeneous type. Characteristically, there was venous permeation preponderance in the differentiated type and peritoneal dissemination preponderance in the undifferentiated type. This evidence of DNA heterogeneity in gastric carcinoma tissues suggests a possible correlation with the metastatic behavior.

Cytophotometry↗

Prognostic factors for noncurative gastric cancer: univariate and multivariate analyses.

We performed univariate and multivariate analyses of possible prognostic factors related to postoperative clinical course of patients with advanced gastric cancer. Noncurative resection was done for 119 patients with hepatic metastasis, peritoneal seeding, extensive lymph node metastasis, or direct invasion to adjacent organs, either alone or in various combinations. In the univariate analysis, 6 of 17 items such as peritoneal seeding, lymphatic invasion, vascular invasion, mode of invasion, extent of lymphadenectomy, and width of serosal invasion significantly correlated to the prognosis. The multivariate analysis indicated that three inherent pathologic factors, mode of invasion, lymph node metastasis, and hepatic metastasis, and one treatment factor, extent of lymphadenectomy, were significant variables predictive of the prognosis and that the prognosis was expected to be very poor in cases of infiltrative type, nodal involvement to tertiary nodes, presence of hepatic metastasis, and lymphadenectomy less than R3. Prognosis in terms of the extent of lymphadenectomy shows that extensive lymphadenectomy (R3) proved to be significantly effective in prolonging survival time, even after noncurative gastrectomy. We recommend extensive lymphadenectomy to prolong survival time for such patients.

Adenocarcinoma↗

Noncurative resection for advanced gastric cancer.

Between 1965 and 1985, 489 patients with advanced gastric cancer who were treated with gastric resection and in whom tumor cells remained after the operation were defined as cases of a "noncurative resection." The clinicopathological features and prognosis of these patients were examined and two groups were prepared: locally advanced cancer and cancer with a distant metastasis. In locally advanced cancer cases, tumor cells remained in the neighboring organs, lymph nodes, and/or resected margins; in those with distant metastasis, peritoneal dissemination and/or liver metastasis were present regardless of whether or not the metastasis was removed, with or without locally noncurative factors. Serosal invasion was prominent and high rates of lymph node metastasis and lymphatic involvement were evident in both groups. The survival rate for patients with locally advanced gastric cancer was better than that of patients with distant metastasis (P < 0.01). Survival time in patients with locally advanced cancer can be lengthened by resecting all of the primary tumor and as much of the metastatic lesions as possible, even if the surgical management is "noncurative." Aggressive postoperative chemotherapy for patients with distant metastasis from a gastric cancer is to be recommended.

Aged↗

5-Fluorouracil's cytotoxicity is enhanced both in vitro and in vivo by concomitant treatment with hyperthermia and dipyridamole.

We obtained evidence that the cytotoxic effect of 5-fluorouracil (5-FU) is augmented when the drug is given in combination with hyperthermia (HYP) and dipyridamole (DP). Nontoxic levels of DP enhanced the combined cytotoxicity of 5-FU and HYP against B16 melanoma and human tumor cells in vitro as measured by the succinate dehydrogenase inhibition (SDI) test. Growth of B16 melanoma that had been subcutaneously implanted into the feet of C57 BL mice was inhibited by treatment with the combinations of 5-FU and HYP, of 5-FU and DP, and of 5-FU, HYP and DP as compared with the administration of 5-FU alone. Treatment with HYP plus DP did not alter the body weight of mice that received 5-FU. The administration of DP plus HYP seemed to render the tumor cells more sensitive to 5-FU. The combination of 5-FU, HYP and DP shows promise for the treatment of patients suffering from malignant disease.

Animals↗