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Biomedical subjects

N Miyanaga

Publications and source records attributed to N Miyanaga.

At least 55 records · Page 3Linked to original sources

[Treatment of elderly patients with urological cancer].

The number of elderly patients with urological cancer is increasing, and it is becoming very difficult for urologists to decide on an appropriate treatment modality for each patient. Physical and socioeconomical problems make it impossible for the patients to accept a standard treatment for their disease. Between 1987 and 1992, 498 patients with urological cancer were hospitalized in our institute. Among them, 51 patients (10%) were 80 years of age or older. The average age of these older patients was 83.2 (80-93) years. There were 41 men, and 10 women. These older patients included 30 with bladder cancer, 15 with prostate cancer, three with renal cancer, and three with renal pelvic and ureteral cancer. The incidence of patients aged 80 or older was 18.5% for prostate cancer and 15.9% for bladder cancer. Eighty percent of these patients had complications such as cardiovascular disease, and fewer patients could be adapted treatment because of their physical condition. The median survival period was 21.6 months, with only 18 of the patients still living at the time of the analysis. Only 11 of the initial 51 patients (22%) still received follow-up treatment in the outpatient clinic of our institute, 10 of whom were lost during the follow-up. Our observations indicate that we should consider both the medical aspects and quality of life when we choose the suitable type of treatment.

Aged↗

Preliminary results of bladder-preserving therapy with definitive radiotherapy and intraarterial infusion of chemotherapy.

PURPOSE: For management of muscle-invading bladder cancer (clinical stages T2 to T4), combined treatment of definitive radiotherapy (RT) and intraarterial (IA) administration of chemotherapy was carried out for local cure and bladder preservation. METHODS AND MATERIALS: Between 1987 and 1990, a pilot study (Protocol-1) was initially conducted in 16 patients to investigate the efficacy of chemoradiotherapy where RT was combined with TURB and continuous IA infusion of cisplatin. We then performed a regimen of possible bladder-preservation treatment (Protocol-2) in which 19 patients were treated with combination of TURB, full-dose RT and one-shot IA infusion of cisplatin and methotrexate. In RT small pelvis irradiation was performed with x-rays followed by proton beam boost irradiation to the original tumor site. RESULTS: Among patients treated on Protocol-1, a tumor-free bladder was observed in 50% (2/4) after 50-76 Gy but only 8% (1/14) after 30-40 Gy. In this regimen, planned cystectomy was performed in 10 patients and 13 patients (81%) are alive. Among 19 patients treated on Protocol-2, 17 patients (89%) are alive and 13 patients (68%) retained intact bladders without any recurrence. There were 3 cystectomies performed because of persistent tumors. Using a conformal mode of proton beam irradiation, a total dose of 60-80 Gy was safely administered with acceptable morbidities. CONCLUSION: In the light of good complete response and survival rates achieved in the patients treated on Protocol-2, the combined treatment of definitive RT and IA administration of chemotherapy is considered as an effective bladder-preserving strategy.

Aged↗

[Phenotypic difference of lymphocytes circulating in tumorous renal artery and renal vein in patients with renal cell carcinoma].

Phenotypic difference of lymphocytes circulating in tumorous renal artery and renal vein in patients with renal cell carcinoma was studied. Fifteen patients with no prior treatment were studied, from whom blood samples were taken at the time of radical nephrectomy. Mononuclear cells separated from tumorous renal arterial and venous blood were analyzed for cell surface markers. CD3, CD4, CD8, CD11b, CD16, CD25, CD57, Leu8 HLA-DR were compared. CD25 positive cells were significantly increased in venous blood than in arterial blood in the kidneys with tumor. No significant difference was found regarding the other surface markers.

Carcinoma, Renal Cell↗

[Promotive effects of intravesical instillation of dimethylsulfoxide on bladder carcinogenesis in mice].

The effect of intravesical instillation of dimethylsulfoxide (DMSO) on bladder carcinogenesis was examined in mice. Experiment 1: Fifty-five female C3H/He mice were administered 0.05% N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) in their drinking water for 8 weeks. In week 9 they were divided into two groups consisting of 25 mice each. Then, under nembutal anesthesia the first group was given weekly intravesical inatillations of 0.1 ml DMSO (minimum 99.0%) for 10 weeks. The second group received no treatment except anesthesia. All mice were killed 30 weeks after the begining of the experiment and their urinary bladder resected for histological examination. The incidence of bladder carcinoma was 93.7% (15.16) and 27.7% (6/22) in groups 1 and 2, respectively. These incidences differed significantly between the two groups. Experiment 2: One hundred and twenty female C3H/He mice were divided into two groups. The first group was given 0.05% BBN in their drinking water for 5 weeks and then tap water. The second group was not given BBN. In week 6, the first group was divided again into three groups (1, 2 and 3) consisting of 28, 26, and 27 mice, respectively. The second group was divided into groups 4 and 5 consisting of 21 and 18 mice, respectively. Under nembutar anaesthesia groups 1 and 4 received weekly intravesical instillation of 0.05 ml DMSO (minimum 99.0%) from weeks 6 to 13, Group 2 received weekly intravesical instillation of 0.05 ml distilled water from weeks 6 to 13. Groups 3 and 5 received no treatment except anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

[Antitumor effect of combined use of purified human natural tumor necrosis factor (N-TNF) and cis-diamminedichoroplatinum (II) (cisplatin) on the implanted bladder carcinoma (MBT-2) in mice].

The antitumor effect of tumor necrosis factor (TNF) in combination with Cis-diammine-dichloroplatinum (II) (Cisplatin) upon implanted bladder carcinoma (MBT-2) in mice was analysed together with the toxicity. Mice were implanted into the bladder wall with about 10(4) cells MBT-2 viable cells. TNF was the purified human natural tumor necrosis factor. The antitumor effects were evaluated by the volume of the tumor thus implanted and the drug-toxicity by the body weight of mice and microscopic as well as macroscopic findings of the main organs. As a result, 1) The toxicity of TNF to mice was not enhanced in a dose-dependent fashion when combined with Cisplatin. 2) The antitumor effect by combination of TNF and Cisplatin was significantly increased compared to control group. 3) The effects of TNF was enhanced in a dose-dependent fashion when combined with Cisplatin. 4) The antitumor effects was confirmed by pathological findings. These results suggest that the combined use of n-TNF and Cisplatin is promising as a clinically effective treatment against bladder cancer in human.

Animals↗

Evaluation of the invasive potential of superficial bladder cancer by adenosine triphosphate measurement.

In order to predict the malignant potential of superficial bladder cancer, in 121 patients with this malignancy adenine nucleotide levels (adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate) and energy charge in bladder cancer cells were determined. The nucleotides were analyzed according to the method of Bücher, and the energy charge was calculated by applying the formula of Atkinson. It was clearly pointed out that superficial bladder tumors, which became invasive and/or metastatic, had higher levels of adenylate compounds than those which became not. Our results show that a high correlation exists between adenine nucleotide content and tumor progression.

Adenosine Diphosphate↗

Intra-arterial chemotherapy for bladder cancer by insertion of catheter from inferior gluteal artery.

Thirty-four patients with locally advanced bladder cancer have been treated with selective intra-arterial infusion of CDDP and/or ADM (IA therapy) prior to planned surgical resection. Follow-up ranged from 25 to 108 months (median 61). Initial tumor stage was cT2 in 10 patients, cT3 in 19 and cT4a in 5. Catheterization technique: gluteal muscles were dissected gently along the muscle fiber to expose the inferior gluteal artery with the patients in prone position, then the catheter was inserted. The tip was wedged in the internal iliac artery below the bifurcation of the superior gluteal artery. ADM 10-20 mg and/or CDDP 10-20 mg were infused once or twice a week. Total dose of ADM and CDDP were 40-580 and 60-240 mg. Thirteen patients received IA therapy + hyperthermia and 8 IA therapy + irradiation. Surgical resection included total cystectomy (22 patients), partial cystectomy (3 patients) and transurethral resection of the prostate (5 patients). Survival rate at 5 years is 57.9% (T2 = 90.0, T3 = 52.1, T4 = -). Eighteen patients are alive with no evidence of recurrences, and 11 patients were free of disease for more than 5 years. Side effects were bone marrow suppression (5 patients), vomiting (4), erosion of gluteal skin (7), and neurotoxicity, such as sensory disturbance in lower extremities or ischialgia (2); treatment was well tolerated in others. In conclusion, our results suggest that intra-arterial infusion of ADM and/or CDDP by insertion of catheter from inferior gluteal artery is safe with minimal systemic side effects, and prolongs survival for invasive bladder cancer.

Antineoplastic Agents↗

[A model of orthotopic transplantation in mice using MBT-2].

We attempted to produce a malignant urinary bladder carcinoma in mice by transplanting MBT-2 cells. MBT-2 carcinoma about 3.0 x 10(3) cells/0.02 ml were successfully transplanted into the bladder wall with an incidence of 80% (20/25) after three experimental weeks. Inoculated tumor cells grew expansively into the bladder cavity from the bladder submucosa, and invaded the muscle layer. We observed that tumors caused gross hematuria and bilateral hydronephrosis. This malignant tumor model in which a tumor is implanted into its original organs seems to be useful for predicting clinical effectiveness in experimental cancer therapy.

Animals↗

[Intra-arterial cisplatin and concurrent radiation for invasive bladder cancer].

Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6 Gy over 3 weeks) prior to a planned cystectomy. Cisplatin, in total 200 mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef. 3 in 1 case, Ef. 2 in 6. Ef. 1b in 1 and Ef. 1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there was no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated.

Aged↗

[Inhibition by proton irradiation on the development of invasive bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in mice].

Fifty-five female C3H/He mice were given 0.05% N-bytyl-N-(4-hydroxybutyl) nitrosamine in their drinking water for 18 weeks. In week 19, eleven mice (group 3) were sacrificed to confirm that they all had bladder carcinoma. The remaining mice were divided into two groups. Group 1 received 20 Gy of proton irradiation over the whole pelvis, while group 2 received no treatment as a control. After 3 weeks all the animals were sacrificed and their bladders were resected to weigh and to examine histologically. The average weight of the bladder, as an index of the tumor volume, was 67.7 mg in group 1, 120.6 mg in group 2 and 106.5 mg in group 3. There was a significant differences (p less than 0.05) between group 1 and group 2. The incidences of superficial (pT1) and deeply invasive (pT2-3) bladder carcinomas were [10/18 (56%) and 8/18 (39%)] in group 1, [3/17 (18%) and 14/17 (82%)] in group 2 and [2/11 (18%) and 9/11 (82%)] in group 3, respectively. These rates of incidence were significantly different (p less than 0.05) between group 1 and group 2. However, there was no significant difference (p = 0.068) between group 1 and group 3. These results indicate that proton irradiation is effective for treatment of invasive bladder carcinoma in mice.

Animals↗

[Superficial bladder cancer: prophylaxis of recurrence and progression].

Superficial bladder cancer has a good prognosis compared with invasive bladder cancer. However, recurrence of the tumor is frequent and tumor stage and/or grade progress at the time of recurrence in many cases. Intravesical chemotherapy has been employed as a prophylactic method after trans-urethral resection (TUR). Although intravesical chemotherapy has been proved to be effective in delaying the first recurrence of tumor after TUR, it cannot improve the ultimate prognosis of superficial bladder cancer. Many primary, solitary, non-invasive (Ta) and grade 1 tumors do not recur or progress in stage and grade. In these cases, prophylactic intravesical chemotherapy is not essential. Bacille Calmette-Guérin (BCG) should be considered superior overall, to any chemotherapeutic agents. Comparative studies will give information about the best clinical schedule for the treatment of superficial bladder cancer.

Administration, Intravesical↗

[Combination therapy of intra-arterial chemotherapy and local hyperthermia for bladder cancer].

Fourteen patients (age range 50-79 mean 64.2) with locally advanced bladder cancer or CIS have been treated with combination of selective intra-arterial infusion of adriamycin (ADM) and/or cisplatin (CDDP) and local hyperthermia, prior to planed surgical resection. The follow-up periods ranged from 33 to 70 months (median 52). Clinical staging was based on biopsy, CT, Echo, chest X-ray, bone scintigraphy, and IVP. The initial tumor stage was Tis in 1 patients, cT2 in 4, and cT3 in 9. Catheterization technique: with the patient in the prone position, the gluteal muscles were dissected to expose the inferior gluteal artery, then catheter was inserted. The tip was wedged in the internal iliac artery below the bifurcation of the superior gluteal artery. ADM 10-20 mg and/or CDDP 10-20 mg were infused once or twice a week, more than eight times during hyperthermia. The total dose of ADM and CDDP were 40-360 mg and 50-360 mg. Local bladder hyperthermia was achieved with a radiofrequency generator. Novatherm IH-500 (Inter-Nova Co. Ltd, Japan). Intravesical temperature was maintained over 40 degrees C for an hour. Surgical resection included total cystectomy (10 patients), partial cystectomy (3) and TUR (1). Of evaluable 8 patients, CR was obtained in 2 patients, PR in 4, NC in 1 and PD in 1. The survival rate (Kaplan Meier method) at 3 years was 71.4% (n = 9) and at 5 years, 62.5% (n = 4). Five patients died, but two of them died of other causes (traffic accident and spinal cord injury). Severe toxicity, consisting of bone marrow suppression (3) perineal erosion (3) and ischialgia (1), was well tolerated. In conclusion, our result suggests combination therapy of intra-arterial chemotherapy and local hyperthermia is safe with minimal systemic side effects, and may prolong survival with invasive bladder cancer.

Aged↗

[Clinical study of proton radiotherapy in urological cancers].

Therapy with proton beam is superior to that with photon beam in concentrating the dose within a lesion. Fifteen patients with urinary malignant tumors were treated by proton irradiation during the period from June, 1985 to March, 1989 at Particle Radiation Medical Center, University of Tsukuba. Four patients were with renal cell carcinoma, five with prostatic cancer and six with bladder cancer. Treatment results were assessed by change in tumor size either three or six months after the irradiation. In all the four cases with renal cell carcinoma, the tumor sizes were found to be unchanged without any enlargement. Of the five cases with prostatic cancer, two showed that the treatment was effective and the tumor sizes in the other three cases were found to be unchanged. In three of the six cases with bladder cancer the tumors disappeared while the treatment was found effective in two other and it did not cause any enlargement of the tumor in the remaining one. Although local control of the tumor was successful in all the cases, one patient with prostatic cancer and three with bladder cancer died of cancer. Various side effects, such as radiation cystitis, were observed. This prospective therapy is expected to replace the conventional photon therapy. However, some improvement is needed to make full use of the advantageous properties in dose distribution. Combination therapy with other general therapy is required for some cases.

Aged↗

[Basic study of nephrotoxicity of antibiotics. I. Studies of the effects of antibiotics on nucleic acids and protein metabolism in rat kidneys].

In order to evaluate the nephrotoxicity by antibiotics, effects of these agents were investigated in terms of protein synthesis and nucleic acid metabolism in the kidneys of Wistar rats. Aminoglycoside antibiotics (streptomycin, kanamycin, gentamycin), tetracycline (doxytetracycline), chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used. These antibiotics were given to the rats for 5 successive days. On the 6th day 14C-6-orotic acid and 14C-1-leucine were administered intraperitoneally. Incorporation rates of these tracers into ribonucleic acid and protein fraction in rat kidney ribosomes (polysomes) were measured. Another experiment was undertaken in vitro by separating the polysome fraction from the rat kidneys. In vitro acellular protein synthesis using these polysomes was established. Effects of antibiotics on the incorporation rates of 14C-1-leucine were examined. Marked reduction of incorporation of these tracers into nucleic acid and protein in vivo and in vitro was induced by aminoglycoside antibiotics. These facts suggest that aminoglycoside antibiotics develop nephrotoxicity by interfering with the metabolism of ribosomal RNA and protein.

Aminoglycosides↗

[Diagnosis of pheochromocytoma by 131I-MIBG scintigraphy].

Between February, 1984, and June, 1988, 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy was performed on 48 patients with suspected pheochromocytoma at our hospital. Whole body image and/or spot images were obtained 24, 48 and 72 hours after injection of 0.5 mCi of 131I-MIBG. In 10 of 12 patients with surgically proven pheochromocytoma, 131I-MIBG was accumulated in the primary and metastatic tumor. 131I-MIBG scintigraphy was negative in 2 patients. One case of renal cyst had the accumulation of 131I-MIBG but the disease could be confirmed. By 131I-MIBG scintigraphy sensitivity was 83% (10/12), and specificity was 97% (35/36). Heart intensity was much higher in patients with nonpheochromocytoma than those with pheochromocytoma. Thus 131I-MIBG scintigraphy proved to be safe, non-invasive and specific in the diagnosis of pheochromocytoma.

3-Iodobenzylguanidine↗

Estimations of the S phase fraction in situ in transitional cell carcinoma of the renal pelvis and ureter with bromodeoxyuridine labelling.

This report concerns the estimation of the S phase fraction (SPF) in situ and its value in predicting the malignant potential of transitional cell carcinoma of the renal pelvis and ureter. Eighteen patients with transitional cell carcinoma of the renal pelvis and ureter were given a 0.5 h intravenous infusion of the thymidine analogue bromodeoxyuridine (BrdU) (500 mg) at the time of surgery to label tumour cells in the DNA synthesis phase. The tumour specimens were stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody as the first antibody. The BrdU labelling index, S phase fraction, was determined by counting the number of bromodeoxy-uridine labelled cells in the tissue sections. All grade 1 tumours had an S phase fraction lower than 10%. The average S phase fraction for non-invasive tumour (12 cases) and invasive tumour (6 cases) were 9.7 and 20.9%, respectively. Two patients with rapid spread of ureteric tumour showed an S phase fraction of 18.4 and 22.3%. The results obtained with the S phase fraction were comparable with histological tumour grade and invasive potential. The higher S phase fraction may indicate greater biological malignancy. We believe that determination of the S phase fraction of transitional cell carcinoma of the renal pelvis and ureter offers a new objective and quantitative assay of the biological potential of individual tumours and might have practical value in their management.

Bromodeoxyuridine↗

[A clinical study of 92 cases of renal cell carcinoma--statistical analysis of prognosis according to the new TNM classification].

A clinico-statistical study was made on 92 patients with renal cell carcinoma who visited us from January 1978 to November 1988. The results were as follows: 1. Seventy-eight patients were treated by radical nephrectomy, two patients by partial nephrectomy, and three patients were treated at other hospitals initially. Nine patients were underwent only conservative therapy. 3. Overall 1, 3, 5, and 10-year survival rates by Kaplan-Meier method were 81.8%, 58.0%, 55.3%, and 50.2%, respectively. 3. The 3-year survival rates according to clinical T-stage were 71.3% for 56 patients in T2, 66.8% for 16 patients in T3a, and 24.1% for 16 patients in T3b. A significant difference existed between patients in T3a and patients in T3b. It appears that the new TNM classification system is more accurate for prognosis of patients in stage T3 than that currently in use.

Adult↗