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Biomedical subjects

K Tsushima

Publications and source records attributed to K Tsushima.

At least 19 recordsLinked to original sources

Correlation of DNA ploidy, histopathology, stage and clinical outcome in gastric carcinoma.

The determination of nuclear DNA ploidy from paraffin-embedded specimens was performed by flow cytophotometry on 277 surgically resected primary gastric carcinomas to assess the relationship of various pathological findings and DNA content with survival. The preparation of samples was performed by a modification of Hedley's technique and the staining method of Vindelov. Eighty-nine (32%) carcinomas were DNA diploid, 69 (25%) were DNA tetraploid, and 119 (43%) were DNA aneuploid. DNA non-diploid patterns were significantly associated with macroscopic ulcerative appearance, location of the tumour in the proximal stomach, histological grade, and advanced stage of tumour. Patients with DNA non-diploid cancers, and specifically DNA aneuploid cancers, exhibited significantly poorer survival than patients with DNA diploid tumours. These data support the prognostic value of tumour DNA content in patients with resected gastric carcinoma.

Carcinoma

Postremission therapy without prednisolone improves survival in adults with acute leukemia.

This prospective randomized clinical trial was to clarify whether postremission therapy without prednisolone (PSL) was more effective than therapy with PSL in improving the 5-year survival of adults with acute leukemia. Thirty consecutive adult patients with newly achieved complete remission were randomized to receive postremission therapy either with or without PSL between September 1985 and September 1988. The patients ranged from 16 to 57 years in age. Patients treated without PSL had a significantly better 5-year survival rate than those receiving PSL according to Kaplan-Meier analysis (53.5% vs 15.3%, p < 0.05). In the group treated without PSL, eight out of 15 patients were alive at 72 months, and seven patients maintained their first complete remission at 72 months. Among patients with acute lymphoblastic leukemia (ALL) who were treated without PSL the median duration of remission was 24 months, and the survival rate at 72 months was 50.0%. On the other hand, the median survival was only 13 months for the 5 patients with ALL treated with PSL. Thus, it is desirable that adults with acute leukemia are treated by postremission therapy without PSL.

Acute Disease

[Effects of prostaglandin E1 and dibutyryl cyclic AMP on hemodynamics after cardiopulmonary bypass in valve replacement surgery].

In view of vasodilating action of prostaglandin E1 (PGE1) and dibutyryl cyclic AMP (DBcAMP) we investigated the effect of each agent on hemodynamics after weaning from cardiopulmonary bypass (CPB) comparing with the effect in control group. PGE1 and DBcAMP were administered to patients who underwent valve replacement surgery with continuous low dose infusion at an average rate of 0.026 micrograms.kg-1.min-1 and 7.25 micrograms.kg-1.min-1 respectively. Following result was obtained. In PGE1 administered group, a significant reduction in pulmonary vascular resistance (PVR) and a significant decrease in mean arterial pressure (MAP) were observed during CBP, while there were no significant differences in other parameters, such as platelet counts, differences between core and peripheral temperature (delta T), urine output, systemic vascular resistance (SVR), cardiac index (CI), right-to-left shunt (Qs/Qt), oxygen delivery (DO2) and oxygen consumption (VO2). However, CI and platelet counts tended to increase but delta T and SVR tended to decrease. In DBcAMP administered group, there were no significant differences in all parameters compared with those of control group, showing a tendency of less improvement in hemodynamics than in PGE1 group. We have shown that the use of PGE1 rather than DBcAMP as vasodilator agent seems advantageous during open-heart surgery in patients especially with severe pulmonary hypertension, but it tends to cause severe hypotension during CPB.

Aged

[A randomized controlled study on imipenem/cilastatin sodium in comparison to aztreonam + lincomycin in treating severe infections in patients with malignant tumors or hematological diseases].

A randomized controlled study was conducted to compare effects of imipenem (IPM) (1.0-1.5 g/day) with those of aztreonam (AZT) (4 g/day) +lincomycin (LCM) (1,200-2,400 mg/day) in patients with malignant tumors or hematological diseases and severe infections. A total of 95 patients entered the study between October 1989 and March 1991. Forty-seven patients were treated with IPM and the remaining 48 patients were given AZT+LCM. No statistically significant differences existed in age, sex or underlying diseases between the 2 groups. Overall, the clinical cure rate of the IPM group was 53%; This was significantly higher than the 31% cure rate obtained in the AZT+LCM group (P less than 0.05). The difference was significant in patients whose granulocyte counts were less than 1,000/microliters, but not in those whose granulocyte counts were 1,000/microliters or higher. Side effects were observed in 5 patients given IPM and one given AZT+LCM. In conclusion, no significant differences appeared to exist regarding clinical efficacy and safety between the 2 treatment regimens.

Adolescent

[Favorable prognoses in 24 adult patients with acute leukemia, surviving over five years since 1985].

Since 1985 we have experienced 24 leukemia cases with long-term survival, who were treated with one of three types of postremission therapy. Of them, 20 patients were physically fit for ordinary work and returned to their work as workers or housewives during long-term follow-up period. Two housewives gave birth. We have devised three types of postremission therapy; 1) multidrug combination therapy with gradually longer intermissions (January 1980-March 1983); 2) controlled randomized clinical trial by the Japanese Foundation for the Multidisciplinary Treatment of Cancer, April 1983-March 1985-March 1988). In a group who underwent multidrug combination therapy without prednisolone, 12 of 20 patients who achieved complete remission have shown continued complete remission, as of November 1991, including seven 5-year survivors. These results indicate that improvement of postremission therapy makes it possible for adult patients with acute leukemia to survive 5 years or longer.

Adolescent

Effects of changes in angiotensin converting enzyme activity on renin release: pretreatment with dexamethasone enhances a plasma renin activity response to captopril in normal subjects.

Healthy adults were given captopril (25 mg and 75 mg) po with or without dexamethasone (DXM) pretreatment (1 mg po 2 h before and simultaneously with the captopril). We determined the serum potassium and sodium concentrations, plasma prostaglandin E2 level, PRA, serum angiotensin converting enzyme (ACE) activity, and aldosterone level from 20 min before to 120 min after administration of captopril. DXM pretreatment stimulated the PRA response to captopril. This stimulation was suppressed by indomethacin. However, the administration of DXM did not induce a consistent rise in the prostaglandin E2 level. The administration of DXM induced a significant rise in the potassium concentration, but since simultaneous administration of indomethacin with captopril induced the suppression of PRA without affecting the potassium level, the PRA increase in response to captopril with DXM was not caused directly by the potassium increase. There were no significant differences in the PRA increase between 25 mg captopril and 75 mg captopril, or between DXM-25 mg captopril and DXM-75 mg captopril, though the inhibitions of ACE activity by captopril differed according to dose. The PRA increases, but not the captopril-induced inhibition of ACE activity, were significantly different between captopril alone and captopril with DXM pretreatment at either dose of captopril. Thus, the inhibition of ACE activity perhaps allows PRA to increase in response to captopril. These results suggest that the DXM stimulation of PRA may have been dependent on the inhibition of ACE activity by captopril.

Adult

[A phase II study of SM-5887 for advanced gastric cancer].

A phase II clinical trial of SM-5887, a new totally synthesized anthracycline derivative, was carried out in 13 patients with inoperable or recurrent gastric cancer. No patient had been given anthracycline previously. SM-5887 was administered by I.V. bolus with a dose of 100 mg/m2 every three weeks. Twelve of 13 cases were eligible and evaluable for the response. Of the 12 evaluated cases, 6 showed no change (NC), including one minor response (MR). The remaining 6 cases showed progressive disease (PD). Adverse effects were relatively mild in most cases and included anemia, leukocytopenia, thrombocytopenia, nausea/vomiting, phlebitis, hair loss and fever. Among them, leukocytopenia was observed most frequently.

Adenocarcinoma

[Cases of advanced cholangiocarcinoma showing partial response by the combination chemotherapy including protracted continuous infusion of 5-FU combined with intravenous administration of low-dose leucovorin and intra-arterial administration of MMC and CQ].

We treated a patient with advanced cholangiocarcinoma with a new combination chemotherapy (modified MQF). The regimen consisted of intra-arterial administration of MMC (20 mg/body) and CQ (4 mg/body), protracted continuous infusion of 5-FU (500 mg/body) and intravenous administration of low-dose leucovorin (30 mg/body). More than 50% reduction in the liver tumor for over 4 weeks was obtained by the therapy. As for toxicity, diarrhea and stomatitis were observed.

Adenoma, Bile Duct

[Seven cases of eye involvement in adult with acute leukemia].

Seven acute leukemia cases with oculomotor paralysis and/or optic nerve paralysis were reported. Five cases were lymphoblastic and two were myelogenous leukemia. The average age was 30.7 years old and male to female ratio was 5:2. The eye involvement developed during hematological complete remission stage in 4 cases, and during relapsing stage in 2 cases. For the remaining case, eye symptom was an initial symptom of the disease. The computed tomography of ocular region showed tumorous involvement in 3 cases and no abnormality in other 4 cases. The white blood cell count on admission was over 30,000/microliters and leukemic cells occupied over 59% of bone marrow nucleated cells in 5 cases. Intrathecal administration, a whole brain irradiation and intra-arterial injection of Nimustin as well as standard systemic chemotherapy were performed against oculomotor and optic nerve involvement. Leucoencephalopathy occurred in 2 of 7 cases after intrathecal administration and irradiation. Since 1980, continuous treatment for prophylaxis of central nervous system leukemia have been done and this protocol was effective for meningeal involvement but not for ocular involvement.

Acute Disease

Carcinoma of the gallbladder. Does radical resection improve outcome?

The records of 111 patients with gallbladder carcinoma operatively treated between 1972 and 1984 were retrospectively reviewed. Fifty-seven percent of patients had distant metastases; another 16% had nodal metastases without distant disease. Median survival was 0.5 years, and 5-year survival was 13%. Clinical jaundice, tumor stage, and tumor grade were all predictive of patient outcome. DNA ploidy, measured in 70 patients, was not a prognostic indicator. In 36% of patients, cholecystectomy (20%) or radical cholecystectomy (16%), which included adjacent liver and regional lymph node resection, was potentially curative. Median survival for patients undergoing radical procedures was 3.6 years, and survival was 0.8 years for patients following cholecystectomy. The 5-year survival rates were comparable (33% vs 32%). While radical cholecystectomy may benefit individual patients and can be accomplished with low morbidity, there was no overall survival advantage compared with cholecystectomy.

Adult

Antitumor effect of combination of murine recombinant interferon beta, murine recombinant interferon gamma and human recombinant interleukin-2 in MethA-bearing mice.

We have previously reported that the combination of murine recombinant interferon beta (Mu-rIFN beta) with murine recombinant interferon gamma (Mu-rIFN gamma) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFN beta with Mu-rIFN gamma on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 x 10(3) U or 5 x 10(4) U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 x 10(5) U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 x 10(3) U and 5 x 10(5) U) in addition to the combination of IFN beta and IFN gamma showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFN beta and IFN gamma had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFN beta and gamma was effective for cancer treatment.

Animals

A novel model of solitary hepatic tumor in rats using ascites hepatoma AH13: suitability for chemotherapeutic studies.

A highly reproducible model of a solitary hepatic tumor in rats using ascites hepatoma AH13 has been developed using a two-step method which was suitable for quantitative chemotherapeutic studies. Diffuse hepatic metastases were induced first by inoculation of three different ascites hepatomas, AH13, AH130 and AH7974 into the portal vein in a dose-dependent fashion. Second, the induced hepatic tumor (3 x 10(7) cells) was minced into 1 x 1 x 4 mm fragments and implanted in the liver of normal rats. In this procedure, the AH13 strain proved best suited for the generation of a solitary hepatic tumor. The growth of the solitary liver tumor using AH13 was highly reproducible. To demonstrate the suitability of this solitary hepatic tumor model for the evaluation of chemotherapy, the tumor-burdened rats were treated with adriamycin (ADR) and mitomycin C (MMC). The reduction in tumor size was proportional to dosage, and the statistical significance of the differences between the treatment group and control group was proportional to dosage. A synergistic effect of ADR and MMC on the tumor also was demonstrated. This model should prove to be a useful tool for the testing of newly developed treatments of hepatic cancer.

Animals

[Factors of gastric lesions following after transcatheter arterial embolization for primary hepatoma].

To clarify the influence of Transcatheter Arterial Embolization (TAE) on the stomach, endoscopic examination was carried out before and after TAE. Forty-six TAE were performed in 27 patients with primary hepatoma. New gastric lesions, erosions and ulcers, were developed in 25 of 46 TAE. There was no significant relationship between the incidence of the lesions in the cases with esophageal varices (15/24) and the cases without (10/22) and there was no significant relationship between the incidence of the lesions after the first TAE (12/22) and after the second TAE (5/14). Period between the first and the second TAE had no statistical influence on the lesions after the second TAE. Hepatic functions (Child's classification; Rmax, K, R15 of ICG; serum total protein; serum albumin; total bilirubin; prothrombin time; hepaplastin test) before TAE were not statistically related to the appearance of the gastric lesions following TAE (Table 1). On the other hand, the cases which showed apparent effects of TAE including 0.2 time decrease of AFP had the more gastric lesions (P less than 0.05) (Table 2). The cases with upper abdominal pain after TAE had more gastric lesions (24/38) than the cases without (2/8) (P less than 0.05). But the cases undergone TAE with high possibility of the influx of gelatin sponge pieces, lipiodol or anticancer agents into the supplying vessels for the stomach did not exhibit significant incidence of the lesions (Table 3). Thus, when TAE is followed by a 0.2 time decrease in AFP, it is necessary to pay more attention to the gastric lesions. The prophylactic administration of H2 antagonist before or just after TAE did not seem useful to prevent the gastric lesions. These findings suggest that the influx of gelatin sponge pieces, lipiodol or anticancer agents to the stomach does not always cause gastric ulcer or erosion.

Aged

Effect of combination of 5-fluorouracil, epirubicin and mitomycin C (FEM) on advanced gastric carcinoma.

Fifteen patients with advanced gastric carcinoma were treated with the combination of 5-Fluorouracil (5-FU), Epirubicin (EPI) and Mitomycin C (MMC). Twelve of 15 patients were evaluable. Three patients showed partial response (25%) and 4 showed no change (33%) according to the criteria of Japan Society for Cancer Therapy. Mean survival time for responders, nonresponders and all evaluable patients were 14. 3, 3.6 and 6.3 months, respectively. Two patients with partial response lived over 18 months. Major toxicities included myelosuppression, nausea and vomiting, and alopecia. These were mild in general and reversible by discontinuance. No cardiotoxicity developed. It was concluded that this combination therapy is beneficial in patients with advanced gastric carcinoma because it showed measurable clinical effectiveness with less toxicity than FAM therapy (a combination of 5-FU, Doxorubicin and MMC).

Adult