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Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 253 records · Page 14Linked to original sources

Prophylactic administration of urinary trypsin inhibitor prevents postoperative hyperamylasemia after R2 gastrectomy in patients with gastric cancer. A prospective randomized trial.

The purpose of this prospective randomized study was to determine whether prophylactic administration of urinary trypsin inhibitor prevents postoperative damage to the pancreas caused by R2 gastrectomy in patients with gastric cancer, by analyzing related enzyme activities. Among the 22 patients who underwent distal partial gastrectomy together with R2 lymphadenectomy, 12 were given the drug for 3 days postoperatively, and 10 no therapeutic agent. These groups were otherwise comparable. Postoperatively, the control patients had significantly higher levels of total amylase activity in the serum and P-type amylase when compared to the preoperative data. These amylase activities almost remained at the preoperative level in those given the drug. When the ratio of increase in enzyme activities (postoperative value divided by preoperative value) were compared, on the 7th postoperative day, total amylase activity in the serum and P-type amylase were significantly different between the two groups (p less than 0.05). This difference was also evident when comparing total amylase activity in the urine (p less than 0.05). These findings indicate that prophylactic administration of urinary trypsin inhibitor would aid in preventing postoperative hyperamylasemia caused by R2 gastrectomy in patients with gastric cancer.

Adult↗

Human hepatocellular carcinoma sensitivity to antitumor drugs assayed using the succinate dehydrogenase inhibition test.

Chemosensitivity of hepatocellular carcinoma tissues from 72 patients to 6 antitumor agents was assayed using the succinate dehydrogenase inhibition test. Sensitivity was positive in 47.2% of tissues exposed to adriamycin, 53.5% to mitomycin C, 10.3% to 5-fluorouracil, 51.5% to cisplatin and aclacinomycin A. respectively, and 52.9% to carboquone. Eight percent of the tissues were sensitive to all 6 drugs, while the resistance rate to all drugs was 36.5%. The remaining 55.5% were sensitive to only some of the drugs. When a comparison of the sensitivity to the 6 drugs was made between two different areas of tumors in 16 patients, positive or negative sensitivity was in a range of 76.9-92.9%. The hypovascular masses seen on the angiography and the histologically well differentiated tumors were resistant to adriamycin, a drug most commonly prescribed to treat patients with liver cancer. For some of these tumors, mitomycin C or carboquone may be effective. Our observation shows that the succinate dehydrogenase inhibition test is useful for determining which drugs will be effective for a particular tumor.

Aged↗

Human colon cancer tissues are more sensitive than rectal cancer tissues to antitumor drugs in vitro.

The chemosensitivities of 62 human colon cancer tissues, 67 rectal cancer tissues and 31 tumor-adjacent normal mucosal tissues were determined using the in vitro succinate dehydrogenase inhibition (SDI) test. These tissues obtained at the time of surgery were exposed to carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was considered as positive when succinate dehydrogenase (SD) activity of the drug-treated cells decreased to below 50% of that of control cells, on day 3 of exposure. Decrease in the SD activity was noted in the colon cancer tissues, compared to the rectal cancer tissues, exposed to six antitumor drugs and in particular, to CQ (p less than 0.05), DDP (p less than 0.01) and ACR (p less than 0.05, one-sided paired t test). Decrease in the SD activity was noted in the tumor tissues, compared to the tumor-adjacent normal tissues, exposed to CQ, MMC and ACR (p less than 0.01). The sensitive rates were higher in the colon cancer tissues than the rectal cancer tissues, against all six antitumor drugs. Our findings show that the rectal cancer tissues are resistant to antitumor drugs, compared to the colon cancer tissues in vitro. When selecting antitumor drugs to treat patients with a rectal cancer, the assessment for chemosensitivity of the related tissues is crucial.

Antineoplastic Agents↗

Sarcoma-180 cells and human colorectal tumor cells under in vitro hypoxic conditions are more sensitive to mitomycin C and carboquone.

The effects of oxygen concentration on the chemosensitivity of mouse sarcoma-180 (S-180) cells and human colorectal cancer tissues to mitomycin C (MMC) or carboquone (CQ) were determined in vitro, since evidence had been obtained that these drugs are more effective in HeLa cells. The results were as follows: (a) S-180 cells exposed to various concentrations of MMC or CQ for 2 h under conditions of normal aeration (about 20%) or hypoxia (5.0% and 0%) were then maintained under normal conditions of aeration for 3 days. Change of viability was assessed by succinate dehydrogenase (SD) activity. With exposure of the cells to MMC or CQ, under anoxic conditions (O2:0%), SD activity decreased to a greater extent than seen in the control cells. The value for CQ was from 61.5% to about 36.2%. (b) The decrease in the SD activity of 20 colorectal cancer tissues kept under conditions of anoxia was compared with findings under normally aerated conditions, following exposure to 30 microM of MMC or 1.6 microM of CQ. On exposure to MMC or CQ under anoxic conditions, SD activity decreased significantly, compared with normally aerated conditions (P less than 0.001 for MMC; P less than 0.05 for CQ). As colorectal cancer is less sensitive than other tissues to various chemotherapeutic agents, we recommend that MMC and CQ be prescribed to treat patients with these malignant lesions.

Alkylating Agents↗

Prognostic factors in adenocarcinoma in the upper one-third of the stomach.

From 1965 to 1985, 356 of 1,468 patients (24.3 per cent) with carcinoma of the stomach who underwent gastric resection had disease arising from the upper one-third of the stomach. Tumors in the upper one-third of the stomach were larger, and gross appearance of types 3 and 4 was frequent. Serosal invasion was prominent, and the rates of metastases of the lymph nodes and liver were higher in carcinoma in the upper one-third of the stomach compared with carcinoma in other regions of the stomach. Palliative resection was done for 43.8 per cent of the patients. Survival rate for patients with carcinoma in the upper one-third of the stomach was lower than for patients with lesions in other regions of the stomach (p less than 0.01). Multivariate analysis indicated that operative curability, hepatic metastasis, serosal invasion, lymph node metastasis, peritoneal dissemination and tumor size are significant prognostic factors for carcinoma in the upper one-third of the stomach. These events, except for peritoneal dissemination, differed between carcinoma in the upper one-third of the stomach and in other regions of the stomach, and the survival rate for patients with carcinoma of the upper one-third of the stomach was less favorable. Early detection is crucial for improving the survival time of patients with carcinoma in the upper one-third of the stomach. Aggressive postoperative chemotherapy should be considered when noncurative resection is done.

Adenocarcinoma↗

Hepatic recurrence not prevented with low-dosage long-term intraportal 5-FU infusion after resection of colorectal liver metastasis.

Seventeen patients with colorectal cancer metastatic to the liver underwent hepatic resection. For five we prescribed adjuvant therapy which included intraportal mitomycin C (MMC) and 5-fluorouracil (5-FU) and consecutive oral administrations of tegafur (N1-(2'-tetrahydrofuryl)-5-fluorouracil), in an attempt to reduce recurrences in the liver. Intraportal chemotherapy consisted of low-dosage, long-term 5-FU infusion, 40 days at 250 mg/day, and a 10 mg bolus injection of MMC at the start and the end of continuous 5-FU infusion. With regard to postoperative events in patients given the infusion therapy, there was no hepatotoxicity or hematologic toxicity, no mechanical complications and no pain or vomiting. Two of five patients given infusion therapy and six of 12 not given the therapy died within 5 years after surgery. There was recurrence in the liver in two patients given infusion therapy and in four not given the therapy. Although low-dosage, long-term intraportal chemotherapy is a safe treatment given hopefully to prevent hepatic recurrence, we found no beneficial effect.

Adult↗

DNA ploidy is a major prognostic factor in advanced gastric carcinoma--univariate and multivariate analysis.

DNA ploidy was determined by cytofluorometric analysis of paraffin-embedded malignant tissue from 96 Japanese patients in whom gastric carcinoma had invaded the serosa. Aneuploidy was found in gastric carcinoma tissue from 63 patients (66%). The postoperative 5-year survival rate of patients with aneuploid malignancy was significantly lower (13%) than those with diploid malignancy (36%) (p less than 0.05). A multivariate analysis of various clinical and pathologic factors showed that tumor size, lymph node metastasis, vascular invasion, and DNA ploidy were significant and independent factors, which correlated with prognosis.

Analysis of Variance↗

Pertinent risk factors and gastric carcinoma with synchronous peritoneal dissemination or liver metastasis.

From 1965 to 1985, of 1108 patients with advanced gastric cancer who underwent gastric resection in our department, 216 patients (19.5%) had synchronous peritoneal dissemination (PD) or liver metastasis (LM). The 1-year survival rate was 22.5% for PD, 14.7% for LM, and 4.8% for PD plus LM (p less than 0.01). With PD, patients were younger, tumor was larger, Borrmann type 3 and 4 and undifferentiated lesions were more frequent, and the incidence of serosal invasion was higher. Histologic findings showed a pattern of infiltrative growth. With LM, patients were more likely to be male, Borrmann type 2 and 3 and differentiated lesions were frequent, and the antral region was often involved. The degree of serosal invasion was less than with PD. The pattern of growth was the expansive type and vascular involvement was prominent. Rate of lymph node metastasis was high in both groups. The route of metastasis was partly linked to features of the primary lesion. Multivariate analysis showed that independent risk factors involved in the occurrence of each metastasis are serosal invasion, lymph node metastasis, and undifferentiated tissue type for PD, and lymph node metastasis and vascular involvement for LM. When designing treatment in an attempt to suppress a recurrence, even after curative resection, all of these risk factors must be kept in mind.

Female↗

Prognostic significance of serosal invasion in carcinoma of the stomach.

Two hundred and seventy-seven patients with advanced carcinoma of the stomach invading the serosa were studied with regard to the relationship between the length of the serosal invasion (LSI) and prognosis, with a division made between expanding and infiltrative types of tumors. Among patients with expanding types of tumors, five year survival rates were 40 per cent in patients with LSI less than 4.0 centimeters, 33 per cent in patients with LSI 4.1 to 6.0 centimeters and 13.0 per cent in patients with LSI more than 6.0 centimeters. Among those patients with infiltrative types of tumors, those with less than 2.0 centimeters of LSI had a better prognosis (five year survival rate of 53 per cent), whereas those patients with a LSI more than 2.0 centimeters had a very poor prognosis (five year survival rate of less than 20 per cent) and the significant LSI on prognosis was found to be 2.0 centimeters. Involvement of the lymph node and metastasis to the liver were not affected by LSI, whereas the rates of peritoneal dissemination and direct invasion to neighboring organs increased with an increase in LSI. Knowledge of these factors facilitates the planning of postoperative treatment.

Follow-Up Studies↗

Lung adenocarcinoma is more sensitive than gastric adenocarcinoma to anticancer drugs in vitro.

The chemosensitivities of 26 lung adenocarcinoma tissues were compared to those of 110 gastric adenocarcinoma tissues, using the in vitro succinate dehydrogenase inhibition (SDI) test. Tumour tissues obtained at surgery were exposed to five different anticancer drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), cisplatin (DDP) and 5-fluorouracil (5-FU). The lung adenocarcinomas showed a statistically significant reduction in succinate dehydrogenase (SD) activity, compared to the gastric adenocarcinomas, after exposure to each drug. The chemosensitivity was defined as a reduction in SD activity to 50% of control or less. Lesser degrees of reduction in SD activity were defined as drug resistance. The sensitivity rates to ADM, MMC and DDP, respectively, were significantly higher in the lung than in the gastric adenocarcinomas. Tumour cells from 22 (84.6%) of the 26 lung adenocarcinoma tissues showed a sensitivity to more than three drugs, whereas the rate was only 46.4% (51/110) for the gastric adenocarcinomas. The rate of resistance to all the drugs tested was 3.8% (1/26) for the lung adenocarcinomas, in contrast to the 20.9% (23/110) seen with the gastric adenocarcinomas. Thus, while adenocarcinomas of the lung and stomach both show clinical resistance to anticancer agents, the chemosensitivity of the lung tissues is greater. In the light of these observations, attention must be directed to improving specific drug delivery systems.

Adenocarcinoma↗

Laser treatment for poor-risk patients with early gastric cancer: post treatment pathology.

Two patients with early gastric carcinoma and who were poor surgical risks underwent gastrectomy following repeated laser endoscopy. Pathological findings of the resected stomach were reviewed. Lesions in both patients were ulcerative, with evidence of destruction of the muscularis mucosae caused by laser irradiation. Complete coagulation did not occur in the case of infiltrative-type involvement of the submucosal layer. Gastrectomy was carried out when the clinical status improved and both patients are now cancer-free. We propose that laser treatment for early gastric cancer should be considered for poor-risk patients.

Adenocarcinoma↗

Lack of relationship between perioperative blood transfusion and survival time after curative resection for gastric cancer.

To better comprehend the relationship between perioperative blood transfusion and survival time after curative gastrectomy for advanced gastric cancer, the authors reviewed retrospectively data on 568 patients treated in their clinics from 1965 to 1983. Of these 568, 195 (34.3%) required no blood transfusion and 373 (65.7%) required transfusions within the perioperative period. Univariate analysis indicated that the survival time of the transfusion recipients was significantly less than that of the patients who had no transfusions (P less than 0.01). In subgroups of the authors' patients stratified to adjust for stage of disease, there was, however, no significant difference between the survival rates. Subsequently, multivariate analysis, using the Cox regression analysis, which adjusted for sex, age, and other covariates, indicated that perioperative blood transfusion was not a useful factor for predicting survival time. Multivariate analysis suggested that tumor size (P less than 0.01), degree of invasion into the gastric wall (P less than 0.01) and status of lymph node metastasis (P less than 0.01) were the most important covariates after curative gastrectomy for advanced gastric cancer. The authors' findings revealed the lack of any relationship between perioperative blood transfusion and survival time of patients who underwent curative resection for advanced gastric cancer.

Blood Transfusion↗

Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer.

The infiltration of dendritic cells determined in 210 patients with gastric carcinoma was investigated from the standpoint of tumor invasion, lymph node metastasis, and prognosis. Dendritic cell infiltration was graded as "slight" and "marked." The 39% frequency in the marked infiltration group at the mucosal stage did not change in proportion to invasion into the deeper layers. The 5-year survival rate was 60.4% in patients with marked infiltration and 38.8% in those with slight infiltration, which was statistically different (P less than 0.01). The difference in survival rates was only statistically significant in those with cancer emerging from the serosa (P less than 0.001). There was a similar incidence of lymph node metastasis between the marked and slight infiltration groups in each grade of tumor invasion. However, marked infiltration of dendritic cells prevented widespread nodal involvement beyond the primary node in cases of advanced carcinoma (P less than 0.05). These findings indicate that infiltrating dendritic cells do not prevent the spread of tumor invasion but do prevent nodal involvement; therefore, for patients with a gastric cancer emerging from the serosa, the prognosis will be good.

Carcinoma↗

[A case report of hemolytic uremic syndrome (HUS) induced by antineoplastic agents].

An autopsy case of hemolytic uremic syndrome after treatment with antineoplastic agents for advanced gastric carcinoma is reported. A 70 year-old woman underwent partial gastrectomy for gastric carcinoma on April 16, 1987 (P0H0S2N4, Stage IV). She was treated with Mitomycin C (MMC), UFT, OK-432 and PSK as post operative chemotherapy. Total doses were 60 mg of MMC, 33.9 g of UFT, 55 KE of OK-432 and (507 g) of PSK. She suffered from occult blood in urine in September 1987, thrombocytopenia and anemia in October, edema and hypertension in November and died due to acute renal failure and pulmonary failure on December 5, 1987. It seemed that the cause of death was hemolytic uremic syndrome induced by antineoplastic agents.

Aged↗

Comparison of pyrimidine nucleotide synthetic enzymes involved in 5-fluorouracil metabolism between human adenocarcinomas and squamous cell carcinomas.

The activities of orotate phosphoribosyltransferase (OPRT), cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd) kinase, thymidine (dThd) kinase, Urd and dThd phosphorylases, and DNA polymerase were examined in the eight human lung squamous cell carcinomas and five lung adenocarcinomas, and five tumor-adjacent normal lung tissues. All of these enzymes are involved in pyrimidine nucleotide synthesis. The metabolism of 5-fluorouracil (5-FU) was determined. The levels of these enzymes, except for OPRT, were high in tumor tissues and almost the same between lung squamous cell carcinomas and adenocarcinomas, with no statistical difference. The activities for phosphorylation and degradation of 5-FU were similar in each tissue type of tumor. As 5-FU is incorporated into tumor cells and is metabolized actively to 5-FU nucleotides in squamous cell carcinoma tissues, at almost the same level seen in adenocarcinoma tissues, this drug should have a wide clinical application.

Adenocarcinoma↗

Serum carcinoembryonic antigen level increases correlate with tumor progression in patients with differentiated gastric carcinoma following noncurative resection.

Serum carcinoembryonic antigen (CEA) levels were determined serially in 30 preoperative and postoperative patients with differentiated and 47 with undifferentiated gastric cancers. Macroscopic noncurative resection of the stomach was done for those patients. There was no difference between survival curves in the differentiated and undifferentiated cases, and the 50% survival was 13.1 months for the differentiated group and 12.5 months for the undifferentiated group. Preoperative serum CEA levels were 10.4 +/- 5.2 ng/ml for the differentiated and 4.0 +/- 1.6 ng/ml for the undifferentiated cases, and CEA-positive rates were 20.0% for the differentiated and 14.9% for the undifferentiated cases. There was no difference in preoperative CEA values with regard to tissue types. In the course of tumor progression, CEA levels increased during the first postoperative year in the differentiated cases and related reciprocally to decreases in survival rates. Little change was noted in the undifferentiated cases. Therefore, the serial postoperative assay of serum CEA levels has predictability with regard to tumor progression in patients with a differentiated gastric cancer.

Adult↗

Adjuvant chemotherapy enhances long-term survival of patients with advanced gastric cancer following curative resection.

We examined the effectiveness of postoperative adjuvant chemotherapy with mitomycin C (MMC), 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), plus PSK, an immunomodulator, for patients with advanced gastric cancer who underwent histological curative resection. The effect of chemotherapy on prognostic serosal (ps) invasion [ps(-) or ps(+)] and lymph node metastasis [n(-) or N(+)] was examined. One hundred eighteen patients were in the no-chemotherapy group and 137 were on the drugs. The median follow-up time for the 86 survivors at the time of analysis was 13.8 years. With regard to prognostic factors, there were no differences between the two groups. Generalized Wilcoxon test of the two survival patterns revealed a P value of .0351, and the survival rate for 15 years was 45.7% for patients in the no-chemotherapy group and 56.9% for those of the chemotherapy group. In particular, adjuvant chemotherapy was effective for patients with ps(-)n(+) (P less than .05) and ps(+)n(-) (P less than .05), but not for those with ps(-)n(-) and ps(+)n(+). Our findings show that the concomitant prescription of MMC, tegafur, and PSK improves the 15-year survival rate for patients with advanced gastric cancer, following curative resection. As the survival rate is low for the patients with ps(+)n(+), an even more aggressive postoperative chemotherapy is recommended.

Adult↗

Chemosensitivity test for carcinoma of digestive organs.

For the chemosensitivity for carcinoma of digestive organs, gastric, colorectal, and hepatic cancer tissues were examined using in vitro succinate dehydrogenase inhibition (SDI) test and in vivo subrenal capsule (SRC) assay. The chemosensitivity varied in the tissue. The origin of an organ tumor, histological differentiation, and difference of primary or metastatic lesions are critical for determining chemosensitivity. Biochemical analysis shows that antitumor drugs have an increased susceptibility in tissues with high activity of pyrimidine nucleotide synthesis.

Antineoplastic Agents↗