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Biomedical subjects

I Fukui

Publications and source records attributed to I Fukui.

At least 19 recordsLinked to original sources

Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response.

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.

Administration, Intravesical

[Adjuvant chemotherapy for invasive bladder cancer. Multicenter study].

During 2 years and 10 months from November 1985 to September 1988, 50 patients with invasive bladder cancer (pT2-4, pN0-2, M0) were treated with total cystectomy followed by adjuvant combination chemotherapy including cis-platinum. In addition, so-called immunopotentiator (OK-432) and Kanpo (Juzentaihoto: TJ-48) were given to the patients in a random fashion to evaluate whether or not these agents had any significant effect on patients' prognosis. The 3- and 5-year survival rates for 48 evaluable patients were 71% and 67%, respectively. Histologic grade of primary tumors and number of cycles of adjuvant chemotherapy administered had a significant correlation to patients' survival: patients with grade 2 anaplasia had a better 3- and 5-year survival rates than those with grade 3 anaplasia, and patients receiving 3 or more cycles of chemotherapy had a better 3-year survival rate than those with 2 or less cycles. pT and pN categories also affected patients' survival, though not statistically significant. Administration of OK-432 or TJ-48 and pre-operative treatment such as irradiation and intra-arterial chemotherapy had no favourable effects on the survival. Side effects of the adjuvant chemotherapy were minimal to moderate and more than 70% of the patients tolerated at least 3 cycles of chemotherapy. It is likely that adjuvant chemotherapy, when given in a post-operative setting, should be repeated at least 3 cycles or more.

Adult

The relationship of ABH(O) blood group antigen expression in intraepithelial dysplastic lesions to clinicopathologic properties of associated transitional cell carcinoma of the bladder.

Paraffin-embedded, giant-step sections of 13 bladders with transitional cell carcinomas were stained with monoclonal anti-A or anti-B antibodies to investigate whether intraepithelial dysplastic lesions are related to obvious tumors. Normal and/or hyperplastic lesions were retained in only eight bladders; severe dysplasia and/or carcinoma in situ were found in all bladders except two. AB-antigen expression was retained in intraepithelial lesions of bladders with invasive carcinoma. Most intraepithelial lesions were AB-antigen negative in bladders with frequently recurrent tumors. In bladders with initially multiple tumors, AB-antigen expression was negative in almost one half of the intraepithelial lesions. Therefore, it appears likely that most multiple or recurrent bladder carcinomas arise from dysplastic cells in intraepithelial lesions which have acquired malignant potential; initially invasive tumors quickly develop from a limited lesion acquiring a high malignant potential without changes of cell phenotype in most intraepithelial lesions.

ABO Blood-Group System

Clinicopathological study of upper urinary tract tumors associated with bladder tumors.

Among 535 cases of urothelial tumors (upper urinary tract and bladder tumors) from 1970 to 1988, 40 had upper urinary tract tumor associated with bladder tumor. Of 40 cases, 18 (45%) were synchronous, 17 (43%) were metachronous with primary upper urinary tract tumor followed by subsequent bladder tumor 18.5 +/- 14.1 (means +/- SD) months later and 5 (12%) were metachronous with primary bladder tumor followed by subsequent upper urinary tract tumor 40.2 +/- 13.6 months later. The incidence (17/52 = 0.32) of bladder tumor occurrence subsequent to primary upper urinary tract tumor was much higher than that (5/465 = 0.01) of upper urinary tract tumor subsequent to primary bladder tumor. The histologic grades of upper urinary tract tumor and associated bladder tumor were consistent in 73%. Except in 1 case, multiple occurrence of upper urinary tract tumor was always observed unilaterally on the side involved. The current results not only support the theory of multicentricity but raise the possibility that tumor cell implantation may play some role at least in the development of bladder tumor subsequent to upper urinary tract tumor.

Carcinoma, Transitional Cell

[Macroscopic tumor thrombus in renal cell carcinoma].

Prognosis of 114 patients treated for renal cell carcinoma from 1972 to 1988 was investigated to evaluate intravenous tumor extension as a prognostic factor. Those in whom presence or absence of macroscopic tumor thrombus was not confirmed were not included in the current patient group. Tumor stages were evaluated according to TNM criteria except that intravenous tumor thrombus was not counted for local staging. Incidence of T3 and T4 tumors, distant metastasis and grade 3 anaplasia (G3) were higher in V+ group (V1 + V2) than in V0 group, which appeared to be a major difference of background making 5-year actuarial survival rates in V1 and V2 patient groups worse than in V0. Therefore, 5-year actuarial survival rates in N0 and M0 cases receiving radical nephrectomy were compared and found 83.3% in V2 group, 54.4% in V1 and 87.3% in V0. Since V1 group included G3 tumors more frequently than the other two groups, 5-year survival rates were further compared after excluding those with G3 tumors and found to be identical among V0, V1 and V2 groups. The current results indicate that macroscopic intravenous extension of renal cell carcinoma is an accompanied phenomenon secondary to high grade and invasive tumors and therefore, not a primary risk factor for prognosis. Accordingly, it is questionable to regard macroscopic tumor thrombus itself as a risk factor for clinical staging.

Adult

[A randomized trial of PVB, VAB-6, BVP regimen versus PEB chemotherapy in patients with disseminated testicular tumors].

During 2 years and 7 months from June, 1985 to December, 1987, a randomized multi-center trial of PVB, VAB-6, BVP regimen (group A) without etoposide versus PEB chemotherapy (bleomycin, etoposide and cisplatinum) (group B) was given to patients with disseminated testicular tumors. Of 34 patients registered, 10 patients were with minimal disease in stages IIA, IIIO and IIIA and 24 with extensive disease in IIB, IIIB2 and IIIC. Seminomas were found in 10 patients, while non-seminomatous tumors in 24. Among groups A and B, there was no statistical difference in clinicopathological profiles. A group patients were given either PVB, VAB-6 or BVP according to the physician's discretion. In groups A and B, 35% and 43% of the patients achieved complete response, and 45% and 50% achieved partial response, respectively. The difference in CR rates among both groups was not statistically significant even when calculated according to the stage or histologic grouping. Salvage treatments mainly with surgical resection of residual tumors after the chemotherapy, however, were more successful in group B (88%) than group A (61%). It appears likely that the higher response of induction chemotherapy in patients with extensive disease made the salvage surgery more successful in group B than in group A. The 3 year survival rate was 100% in group B, whereas it was 76% in group A. Although the incidence of myelosuppression and alopecia was significantly higher in group B, neuropathy was significantly more frequent in group A. From the above results, PEB seems to be a better induction chemotherapy than the conventional one for advanced testicular tumors.

Antineoplastic Combined Chemotherapy Protocols

[BEP (bleomycin, etoposide, cisplatinum) chemotherapy as an induction therapy of advanced extragonadal germ cell tumor].

Five patients with advanced extragonadal germ cell tumor (EGGCT) were treated with cisplatinum + vinblastine + bleomycin (BVP) or cisplatinum + etoposide + bleomycin (BEP) chemotherapy as an induction therapy. All patients had high levels of tumor markers and multiple distant metastasis in poor nutritious conditions. Two patients given BVP therapy died 6 and 9 months after the chemotherapy. By contrast, three patients given BEP therapy achieved complete remission and were surviving longer than one year without any evidences of disease. Granulocytopenic fever was seen soon after the first course of BEP therapy. Prophylactic granulocyte-colony stimulating factor (G-CSF) treatment, enabled two of them to receive full dose chemotherapy without any fever attacks. In conclusion, BEP chemotherapy is effective to EGGCT as well as far advanced testicular tumors and G-CSF treatment is useful for achievement of induction chemotherapy to advanced germ cell tumors.

Adult

[Studies on 13 cases of double gammopathy].

By a combined use of immunoelectrophoresis and immunofixation, we detected 13 cases of double gammopathy among 269 cases of monoclonal gammopathy investigated between 1986 and 1990. The incidence of double gammopathy (4.8%) was greater than that in previous studies. Double gammopathy was classified into 5 groups: (1) identical pairs of both heavy (H)- and light (L)-chains (1 case); (2) identical H-chains and different L-chains (2 cases); (3) different H-chains and identical L-chains (3 cases); (4) different pairs of both H- and L-chains (5 cases); and (5) monoclonal immunoglobulin and Bence Jones protein of different type (2 cases). An additional M-component was detected during the course of illness in 2 of the 13 cases. As to H-chain combinations, a pair of IgG and IgA (46%) was most frequently encountered. Seven patients had myeloma, three benign double gammopathy and two macroglobulinemia. One case of benign double gammopathy developed IgA (lambda) myeloma three years after the diagnosis. Serum and urine immunofixation is a useful method to detect a trace amount of M-component and to follow up the clinical course of monoclonal gammopathy.

Adult

[Treatment methods as a prognostic factor in eight patients with urachal carcinoma].

Between 1960 and 1982, 8 patients with urachal carcinoma underwent segmental resection of the bladder or en bloc resection, and their five-year survival rate was 50%. One patient each with well, moderate and poorly differentiated adenocarcinoma and one patient with transitional cell carcinoma, died of cancer from 6 months to 2 years and 2 months after operation (mean duration: 1 year and 3 months). The patient with well differentiated adenocarcinoma underwent en bloc resection and was recognized to have peritoneal involvement of the tumor at the operation. The remaining three patients were diagnosed to have tumors confined to their bladder and urachal remnant and were treated with segmental resection of the bladder. Two patients each, with well and moderately differentiated carcinoma confined to their bladder and urachal remnant, were treated with en bloc resection and have been surviving from 8 years and 5 months to 24 years and 10 months (mean duration: 13 years and 7 months) postoperatively as of Dec. 1987. Therefore, patients with well and moderately differentiated adenocarcinomas confined to the bladder and the urachal remnant could be expected to survive longer by en bloc resection.

Adenocarcinoma

[Two cases of urachal cyst].

Case 1: A lower abdominal large painful mass was recognized by palpation, CT scan and ultrasonography in a 64-year-old house wife. Urine cytology was negative. The mass at the dome of bladder was covered with normal epithelium cystoscopically. Aspiration cytology of the lower abdominal mass demonstrated no malignancy and total excision of urachal remnant with a portion of bladder wall was carried out. Histologically, the mass was an urachal cyst with granulomatous change infected with C group beta-streptococcus. Case 2: A 46 year-old male engineer complained of asymptomatic hematuria. Cystoscopic examination revealed a small bleeding lesion at the dome of bladder. Urine cytology was negative. CT scan and ultrasonography revealed a tiny cystic mass lesion with irregular density. Biopsy or aspiration cytology appeared difficult because of the size and localization of the mass. En bloc segmental resection of urachal remnant was carried out. Since intraoperative rapid histological examination of the specimen confirmed no malignancies, dissection of pelvic lymph node was not performed. Urachal cysts presented above were suspicious of malignant degeneration from findings of imaging examination. Either preoperative or intraoperative histological examination in such cases appears to be indispensable to avoid unnecessary extensive operation as well as to perform radical operation required for malignant lesions.

Cytodiagnosis

Inhibitory effect of testosterone on gap junctional intercellular communication of human transitional cell carcinoma cell lines.

A dye transfer method was applied to investigate the effect of testosterone on gap junctional intercellular communication (IC) of two kinds of human transitional cell carcinoma cell lines, JTC-30 and JTC-32. When JTC-30 cells were cultured with testosterone at nontoxic concentrations (17-69 microM), a dose and time dependent inhibition of dye transfer was observed. More than 90% inhibition occurred after exposure to 69 microM testosterone for 96 h. The inhibition was reversed rapidly after testosterone deprivation. Similar results were obtained with JTC-32 cells. 17 beta-Estradiol showed no inhibitory effect on IC of both transitional cell carcinoma cell lines even at toxic levels. Testosterone exhibited no inhibitory effect on IC of human fibroblasts. The inhibitory effect of 5 alpha-dihydrotestosterone was almost similar to that of testosterone. At concentrations examined, cyproterone acetate influenced neither dye transfer nor the inhibitory effect of testosterone, suggesting a mechanism of testosterone action different from that of the known receptor system. Since blockage of IC has been indicated as one reliable evidence for tumor promotion, current results suggest that testosterone is a possible endogenous promoter of the bladder carcinoma and may therefore possibly play a role on the sexually different incidence of bladder carcinoma.

Carcinoma, Transitional Cell

Significant amount of multicatalytic proteinase identified on membrane from human erythrocyte.

Multicatalytic proteinase (MCP) was solubilized from human erythrocyte membrane with 0.1% Triton X-100 and purified to homogeneity using a combination of DEAE-cellulose, hydroxylapatite, and Ultrogel AcA34 chromatographies. This membranous MCP had similar properties to MCP purified in parallel from the cytosol. Both MCPs had a molecular mass of 570 kDa, were composed of apparently nine subunits of 22-36 kDa and had trypsin- and chymotrypsin-like activities. These activities were latent and required heating for the induction. However, slight differences were observed in the effects of reagents (DFP, monoiodoacetic acid, Mg2+, and Ca2+) between membranous and cytosolic MCP. The amount of MCP identified on membranes was estimated to be three-quarters or one-half of that found in the cytosol based on its trypsin- or chymotrypsin-like activity, respectively.

Catalysis

[Autoshaping of a button-push response and eye movement in human subjects].

Two experiments were conducted with human subjects to investigate the similarities and differences between animal and human behaviors under autoshaping procedures. In these experiments, light served as CS, and display on TV served as US. Whether the pushing button response or gazing response to CS could be obtained in human subjects under Pavlovian conditioning procedure was examined. In Experiment 1, uninstructed naive subjects were placed in a room containing a push-button and a TV display. Within the experimental sessions, the push-button was lit for 8 s as CS, and then paired with the display of a soft pornographic program on TV for 10 s. The result indicated that the modeling of pushing button promoted the increase of response probability among the subjects. The trials conducted after the rest period indicated an increase of response probability. In Experiment 2, a 4 cm square translucent panel was lit for 20 s as CS, and then paired with the display of a computer graphic picture on TV for 8 s as US. Some subjects started gazing at the CS for several seconds. These results indicated that some subjects could acquire the gazing response under the autoshaping procedure.

Adult

[Multiple urothelial cancers accompanied by acquired cystic disease of the kidney in a long-term hemodialysis patient].

A 41-year-old miller undergoing hemodialysis for 9 years presented with recurrent episodes of asymptomatic gross hematuria of a 7 years' duration and left flank pain with slight fever of a four months' duration. CT scans revealed bilateral acquired cystic disease of the kidney (ACDK) and a mass (phi 4 cm) in the medial portion of the left kidney, which was angiographically a hypovascular tumor. Cystoscopic examination revealed multiple papillary tumors arising from the entire bladder wall. These findings suggested that the renal mass was a renal pelvic tumor. Bilateral nephroureterectomy with left paraaortic lymph nodes dissection and radical cystectomy were carried out, followed by urethrectomy two weeks later. Histologically, multiple papillary transitional cell carcinomas with G2 greater than G3 anaplasia were found in the left renal pelvis, the lower portion of the left ureter and the bladder. The tumors were predominantly superficial, although the renal pelvic one focally invaded into the muscular layer. Lymph node metastasis and renal cell carcinoma were not recognized. Postoperative course was uneventful with normal blood pressure, though anemia was slightly progressive. He has been free of disease for six months.

Adult

[Relation of tumor number to clinical course of superficial papillary bladder tumors].

Clinical courses of 293 patients with superficial papillary bladder tumors were analysed on the basis of tumor number at the first presentation. The follow-up period ranged from 6 to 266 months with a median of 59 months. 171 patients (58%) had a single tumor, while 122 (42%) had multiple tumors. Those older than 60 years occupied 68% in the latter group and 51% in the former (p less than 0.01). High grade tumors were more frequent in the latter than the former (p less than 0.05). The five-year recurrence rate was 68% for the latter and 39% for the former single tumor group (p less than 0.01). Malignant progression was observed in 3.6% of patients with a single tumor and 13.4% of those with multiple tumors (p less than 0.01). The results would offer a theoretical background to the finding of a poor ten-year actuarial survival rate of 54% for multiple tumor group compared with 76% for the single tumor group (p less than 0.05). However, the rate of primary cancer death was similar in both groups.

Adult

[Discriminant analysis of quantification theory on prognostic factors of chemotherapeutic effects on advanced testicular cancer. East Japan Testicular Tumor Study Group].

Prognostic factors of chemotherapy against advanced testicular cancer were analysed in 33 cases studied by East Japan Testicular Tumor Study Group. In this study a discriminant analysis of quantification theory (a multivariate analysis) was adapted, taking 7 factors as comparative variables. The significant factors for complete tumor response were clinical stage, histology, and tumor markers (HCG-beta, AFP). Prognostic score was calculated in each case by quantification theory, which correctly discriminated the group with CR from that without CR, at a probability of 90.1%. The results of our study indicate that the outcome of chemotherapy on advanced testicular cancer may be predicted with probability, by patients' status and adopted treatment. It may enable one to make an adequate treatment schedule for each patient.

Antineoplastic Combined Chemotherapy Protocols

[A study of cytokeratin in human normal bladder epithelium and bladder carcinoma cell lines].

Normal epithelial and carcinoma cells of human bladder were investigated for the cytokeratin which is one of the intermediate filaments and comprises cytoskeleton using the immunofluorescence method. Carcinoma cell lines used were JTC-30, JTC-32, HUB-41 and T-24. In normal urothelium, keratin fibers were fine and straight with unchanged diameter and distributed regularly in the cytoplasm. By contrast, keratin fibers in bladder carcinoma cells were kinked and changed in diameter and were distributed irregularly in the cytoplasm. The above findings were most obvious in T-24 which formed undifferentiated carcinoma when transplanted to nude mice, and keratin fibers were dominantly located in the perinuclear area. The changes of keratin fibers appeared to be parallel to the grade of histological anaplasia of the tumor formed by implantation of bladder carcinoma cell line cells to nude mice. These observations suggest that the morphology of cytokeratin is a useful indicator for evaluating the grade of malignancy in transitional cell carcinoma.

Animals