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Biomedical subjects

H Tsujihashi

Publications and source records attributed to H Tsujihashi.

At least 19 recordsLinked to original sources

Clinical assessment of carcinoma in situ of the human urinary bladder.

Recent interest in intravesical instillation of bacillus Calmette-Guérin for the management of carcinoma in situ (CIS) of the bladder prompted us to review our results of total immediate cystourethrectomy. From 1975 to 1987, we surgically treated 302 patients with primary bladder tumours. Of these, 21 bladder tumours were histologically diagnosed as CIS, and total immediate cystourethrectomy was performed in all cases. The lesions were classified into three types: primary CIS accompanied by neither previous nor simultaneous tumours of the urinary tract (Type 1, 9 patients), concomitant CIS associated with superficial papillary tumour (Type 2, 6 patients), and secondary CIS detected during the follow-up period after treatment of the superficial papillary tumour (Type 3, 6 patients). Primary CIS was more often diagnosed according to subjective symptoms such as micturition pain than concomitant CIS. Secondary CIS was diagnosed in all patients by routine examinations including cytology and cystoscopy. There was no particular relationship between the time of recurrence of the tumour and the occurrence of secondary CIS. Within the same period, 60 patients with stage T1 bladder tumour were treated by total cystourethrectomy. The actuarial 5-year survival rate was 77% for T1 and 75% for CIS. The 5-year survival rate was 71% for Type 1, 83% for Type 2, and 67% for Type 3 CIS with no difference among the CIS types. Tumour invasion to the bladder, prostate, ureter, or lymph nodes was observed in 9 (42.9%) of the 21 patients, although cystourethrectomy was performed within 3 months of the diagnosis. Examination of ABH antigens did not allow prediction of invasion of CIS. Our findings suggest that the invasive potential of CIS may seriously limit the indications of conservative treatment against carcinoma in situ.

Adult↗

Growth fraction of human bladder tumors.

The growth fraction of bladder tumors was immunohistochemically assessed in situ using anti-DNA polymerase (Pol alpha) monoclonal antibody. This enzyme is known to be present in the nucleus of the cells in G1, S, and G2 phases. The percentage of labeled cells was expressed as the labeling index (LI). The average LI was 6.0% in normal epithelium and 17.8% in bladder tumors, this difference being significant. The labeled cells were distributed throughout both the basal and surface layers of bladder tumors. However, in some bladder tumors, the distribution of Pol alpha-labeled cells varied from area to area. The higher fraction of labeled cells was found in high grade or invasive tumors. Papillary and nodular bladder tumors showed a greater rate of cell proliferation than papillary tumors. These findings suggest that Pol alpha immunostaining could be a potent tool for easy and quick evaluation of proliferating cells in bladder tumors, thereby providing a supplement to conventional histological findings.

Aged↗

Analysis of tissue ABH antigens in superficial bladder tumours.

The determination of ABH blood group antigens for the prognosis of superficial bladder tumours was evaluated. A total of 114 cases of superficial bladder tumours were studied, and all cases were treated by transurethral resection (TUR). The 5-year recurrence rate was 42%. The ABH antigenicity provided more useful information than the grade in predicting recurrence of the tumours. The period from the initial TUR till the first recurrence in antigen-negative tumours was 17.5 months, which was shorter, though not significantly, than the corresponding period in antigen-positive tumours of 25.2 months. In addition, the presence or absence of isoantigens of tumours having two or more recurrences was examined individually.

ABO Blood-Group System↗

Enhancing effect of partial cystectomy on rat urinary bladder carcinogenesis.

The effects of 5% and 50% partial cystectomies on bladder tumorigenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) were investigated in Wistar rats by examining the histological findings and cell proliferative activity. The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in-vitro labeling technique. After eight weeks of treatment with drinking water containing 0.05% BBN, 5% or 50% partial cystectomy was performed at the end of week 16, and the resected bladder was sutured with dexon or silk. There was no difference in the incidence of papillary or nodular (PN) hyperplasia between the control and partial cystectomy groups. However, the incidence of cancer in the group given partial cystectomy was much higher than that in the control. All the cancers in the control group were grade-1 superficial tumors, whereas grade-2 or invasive tumor was observed in six of 40 animals in the partial cystectomy group. The 31.0% labeling index of cancer in the partial cystectomy group was greater than the 24.1% in the control group. There was also a significant difference in the number of BrdUrd-labeled cells in PN hyperplasia between the control and partial cystectomy groups. These findings indicate that partial cystectomy enhances BBN-initiated bladder carcinogenesis and the increase in DNA synthesis found in PN hyperplasia and cancer may be associated with the induction of bladder tumors.

Animals↗

Cell proliferation of human bladder tumors determined by BrdUrd and Ki-67 immunostaining.

The cell proliferation of bladder tumors was assessed in situ using BrdUrd (bromodeoxyuridine) and Ki-67 immunostaining. BrdUrd is incorporated into S-phase cells, and Ki-67 monoclonal antibody recognizes a nuclear antigen present in proliferating, but not resting cells. The percentage of labeled cells was expressed as the labeling index (LI). The average BrdUrd LI obtained applying this method to normal epithelium and to transitional cell carcinoma were 4.1% and 13.1%, respectively, while the Ki-67 LI had average values of 6.2% and 17.8%, respectively. Labeled cells were distributed throughout both the basal and surface layers of transitional cell carcinoma. In general, the value of the BrdUrd LI was correlated to that of the Ki-67 LI. A relatively large fraction of labeled cells was found in high grade or invasive tumors. Bladder tumors with lymph node involvement had higher LI than those without. In addition, a high frequency of S-phase cells within tumor tissue appeared to indicate a great potential for malignancy and thus a poor prognosis. These findings indicate that immunostaining with BrdUrd and Ki-67 may be useful tools for easy and quick evaluation of proliferating cells in bladder tumors.

Adult↗

Assessment of the long-term results of ileocecal conduit urinary diversion.

We reviewed our 12.5-year experience with ileocecal conduit (ICC) and report the long-term results of 147 cases of ICC compared with those of our 102 cases of ileal conduit (IC). We usually performed ICC following total cystectomy for carcinoma of the bladder, while we chose IC in cases of high stage or recurrent malignancies. The average follow-up period was 41.7 months in the ICC group and 28.8 months in the IC group. The postoperative mortality (6.1%) and the incidence of early complications (21.1%) in the ICC group were comparable with the reported incidences for IC. In the later period, stomal problems were most frequently encountered. Urinary tract complications are important because they affect renal function in the course of a long period of time. Excretory urogram showed a satisfactory result and serum creatinine remained within the normal limits even in patients followed up for a long time in both groups. The incidences of pyelonephritis and urinary stones in the ICC group were 13.6 and 5.4%, respectively. We had expected a much lower incidence of these complications and ICC could not cover all the drawbacks of IC. However, at present, there is no ideal or perfect method of urinary diversion, ICC should be one of the acceptable options which has a satisfactory long-term result.

Adolescent↗

Effect of endocrine therapy on a brain metastatic lesion of prostatic carcinoma.

We describe a 62-year-old male with brain metastasis from prostatic carcinoma, which regressed with medical and surgical endocrine therapies. The patient's presenting complaints were left periocular and deep ocular pain and a defect of the left visual field. During treatment of the above symptoms, macrohematuria, dysuria and pollakiuria occurred. Pathological examination of a transrectal needle biopsy disclosed moderately differentiated adenocarcinoma of the prostate. Computerized tomographic scan (CT) and magnetic resonance imaging demonstrated a brain tumor at the frontal skull base and the region of the frontal lobe suspected to be a metastasis of the prostatic carcinoma. One week after a period of daily administration of estramustine phosphate sodium, the prostate was observed to be softened and slightly decreased in size. The visual field defect and disturbance of urination gradually improved. The prostate decreased to normal size and no tumor mass could be detected on the brain CT after 3 months of treatment.

Adenocarcinoma↗

Anti-tumor effect of intravesical instillation of OK432 against rat bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.

The anti-tumor effect of OK432 instilled into the bladder was evaluated in rat bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). In experiment I, the rate of the natural killer (NK) activity was determined with cells from spleen and mesenteric lymph nodes. Intravesical OK432 instillation enhanced NK activity; however, this activity was not dose-dependent and was not augmented by OK432 inoculation into the foot pad. In experiment 2, the therapeutic effect of intravesical OK432 instillation was examined in rat bladder tumors induced by BBN. OK432 was instilled weekly for six weeks. Rats given BBN for 10 weeks were divided into six groups: 1) control; 2) saline; 3) OK432 0.05 KE/ml; 4) OK432 0.05 KE/ml bladder instillation with 0.01 KE/ml foot pad inoculation; 5) OK432 0.05 KE/ml, every other week; and 6) OK432 0.5 KE/ml. Weekly OK432 instillation significantly reduced tumor weight and the incidence of tumor development; however, this inhibition was not dose-dependent and was not enhanced by OK432 inoculation into the foot pad. In rats given OK432 weekly, the augmentation of NK activity and increase in tissue infiltrating lymphocytes were significant. These results suggest that intravesical OK432 instillation is effective in the management of superficial bladder tumors. The study further emphasizes that the dose and method of administration are critical variables in determining the efficacy of immunotherapy.

Administration, Intravesical↗

The kinetics of cellular proliferation in rat urinary bladder treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The cellular proliferation of the bladder epithelium was determined sequentially in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in vitro labeling technique. The percentage of labeled cells was expressed as the labeling index (LI). The average LI values in normal subjects and cancer-bearing subjects were 5.1(%) and 24.2(%) respectively. With the transition of the bladder epithelium from simple hyperplasia to cancer, the LI values of the bladder epithelium were increased. Cases of papillary or nodular (PN) hyperplasia were divided into two types according to the localization of the BrdUrd-labeled cells. The LI in PN hyperplasia was 12.4(%); the difference from cancer was significant. In another experiment, the effect of partial cystectomy on bladder tumors was examined. The group with partial cystectomy showed increases in grade and stage of cancer, and the LI of cancer was more than that in the group without partial cystectomy. The results indicate that partial cystectomy may play a role as promotor for bladder tumors. The current study may be of more practical value than is the conventional one for investigating the histogenesis and progression of human bladder cancer.

Animals↗

[A clinical evaluation of lymphography in bladder tumor].

A study was conducted in a total of 51 patients with urinary bladder tumor who had received surgical operation associated with removal of regional lymph nodes after lymphography. Abnormal findings were observed in lymphogram of 22 patients. The other 29 patients showed no such abnormality. After the operation pathological metastasis was confirmed in 7 patients. Lymphograms of these patients ith positive lymphatic metastasis revealed filling defects in 85.7% and collaterals in 57.4%. There as correlation between the occurrences of these two findings based on quantification analysis III of multivariate analysis. Lymphography before operation showed 87.5% of sensitivity, 65.1% of specificity and accuracy of 68.6%, not having higher accuracy compared to other studies. These results suggest that lymphography, which may have clinical significance, is not a decisive method in exploration of bladder tumor. Comprehensive analysis of diagnostic imaging should be performed, including CT after lymphography.

Female↗

Cell proliferation of human bladder tumors.

The cell proliferation of bladder tumors was assessed via an immunohistochemical technique using anti-bromodeoxyuridine (BrdUrd) antibody. The incorporation of the thymidine analogue, BrdUrd, into DNA synthesis phase was performed by an in vitro labeling technique. The percentage of labeled S-phase cells was expressed as the labeling index (LI). Discrimination between BrdUrd-labeled and unlabeled cells was easy because of the absence of background staining. The average LI obtained using this method in normal, normal epithelium bearing bladder tumors and cystitis was 5.0%, 4.0% and 5.0%, respectively. On the other hand, LI in bladder tumors was 13.0%, while the difference from non-malignant bladder epithelium was significant. As in high grade tumors, the labeled cells distributed throughout both the basal and surface layers of epithelium, compared to low grade tumors and controls. However, there was some variation in the distribution pattern within the same tumor depending on the histological site. On the other hand, the higher S-phase fraction was found in high grade or invasive bladder tumors. Bladder tumors with lymph node involvement had higher LI than those without the involvement. In patients who underwent TUR, the LI was as high as 10.0% in the recurrent group compared with 7.3% in the non-recurrent group. Moreover, in the total cystourethrectomy group, higher LI's were obtained in a patient dying of cancer (20.0%) and a patient with postoperative metastasis (21.0%) than in the non-recurrent group (14.8%). The high frequency of S-phase cells within tumor tissue appears to indicate a more malignant potential and thus a poor prognosis. Although further studies are required for its full significance, the measurement of BrdUrd labeling index by in vitro labeling method promises to afford useful information regarding the biological behavior of bladder tumors.

Adult↗

Immunoresponse of tissue infiltrating lymphocytes in bladder tumors.

Local immunocompetence was evaluated immunohistochemically in patients with bladder tumors before and after local injections of an immunomodulator. The subpopulations of tissue infiltrating lymphocytes (TIL) were examined by staining six serial sections with Leu4, Leu7, Leu10, LeuM3, OKT4, and OKT8 antibodies. T cells predominated over B cells in 19 of 25 bladder tumors. T cell infiltration was prominent around tumor cells, and it was marked in non-invasive tumors. B cells were rare in the stroma. In patients with low-stage tumors, OKT8 cells were more prominent than OKT4 cells. NK cells accumulated within cancer nests but their infiltration was scanty in invasive bladder tumors. Before surgery, immunomodulators (OK-432, IL-2) were injected intratumorally. Their administration resulted in marked increase of T and NK cells, irrespective of the stage of disease; there was a slight increase in B cells. These findings suggest that local immunosurveillance plays a role against bladder tumors. Further studies are required to elucidate host immune responses in the microenvironment of the cancer site, as well as the systemic immune reaction.

Adjuvants, Immunologic↗

Immunohistochemical detection of tissue-infiltrating lymphocytes in bladder tumors.

Local immunocompetence in patients with bladder tumors was evaluated immunohistochemically using monoclonal antibodies. As well as investigating the subsets of peripheral blood lymphocytes by flow cytometry, the subpopulations of tissue-infiltrating lymphocytes were investigated in frozen specimens from bladder cancers (n = 25) and from noncancerous tissues (n = 4). Six serial sections were stained with Leu4, Leu7, Leu10, LeuM3, OKT4, and OKT8 antibodies, respectively. Marked lymphocytic infiltration into bladder tumors was a favorable prognostic sign. T cell infiltration was marked in the noninvasive group and was prominent around tumor cells, whereas B cells were rare in the stroma. T cells predominated over B cells in 19 of 25 bladder tumors. In patients with low-stage tumors, OKT8 cells were more prominent than OKT4 cells. NK cells accumulated around the cancer cells and infiltrated within cancer nests; NK cell infiltration was scanty in high-stage cases. There was a slight scattering of macrophages in 13 cases. In contrast to the findings in subsets of tissue-infiltrating lymphocytes, subsets of peripheral blood lymphocytes did not correlate with stage of disease. These findings suggest the presence of local immunosurveillance against bladder tumors. To elucidate host immune response against tumor, it may be important to characterize tissue-infiltrating lymphocytes.

Antibodies, Monoclonal↗

Role of natural killer cells in bladder tumor.

The role of natural killer (NK) cells in bladder tumors was assessed from the aspect of local and systemic immune responses. The NK cell activity was measured in a 4-hour 51Cr-release assay. The NK activity in patients with bladder tumor was lower, though not significantly, than that in normal individuals. In patients with bladder tumor, the NK activity was significantly lower in invasive tumors and lymph node metastases. Moreover, the NK activity was lower in those who died (n = 4) than it was in survivors (n = 21). In an in vitro experiment, OK432 significantly augmented the NK activity in peripheral blood lymphocytes (PBL), however, this augmentation was not always OK432 dose-dependent. The augmented NK activity induced by OK432 occurred even in patients with invasive tumors. On the other hand, the spontaneous NK activity in tissue-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) was significantly lower than that in PBL. In these three groups, the NK activity was significantly increased by OK432, this rate of increase was highest in TIL, followed by LNL and PBL. Further studies are required to elucidate the role of NK cells in bladder tumor, from the aspect of local and systemic immune responses.

Aged↗

[Clinical assessment for 152 total cysto-urethrectomized bladder cancers].

During the period from July 1975 to September 1987, 325 patients with bladder tumor were treated in Kinki University. 152 of them were treated by total cystourethrectomy. On these 152 cases clinical assessment was performed from several aspects. The 152 patients consisted of 111 males and 41 females. The overall mean age was 64.6 years old. Tumor with the grade G1 was found in 14 patients, G2 in 65 and G3 in 73. As for the stage, CIS was seen in 21 patients, T1 in 60, T2 in 22, T3a in 23, T3b in 15 and T4 in 11. The 5 year survival rate of the total patients was 62%. The rate by grade was 78% in G1, 66% in G2 and 55% in G3; the rate by stage was 75% in CIS, 77% in T1, 59% in T2, 57% in T3a, 36% in T3b and 13% in T4. When the stage became T3b, the survival rate fell remarkably. Lymphadenectomy was performed in 136 of the 152 patients and metastasis was observed in 19 patients of the former. Their 5 year survival rate was 22% in patients with lymph node involvement and 70% in those without lymph node involvement; the difference was significant. Furthermore, the relation between the macroscopic appearance and the survival rate was studied. The size, multiplicity and growth pattern (papillary or nodular) were likely to be related to the survival rate of bladder tumors. We believe that these clinical assessments for bladder tumors will contribute to an improvement of the therapeutic results for the tumors together with studies on their natural history.

Aged↗

[Anti-tumor effect of LAK (lymphokine activated killer) cells against human bladder tumors transplanted to nude mouse].

The effect of lymphokine-activated killer (LAK) cells on bladder tumor was examined in vivo and in vitro. In the in vitro experiment, 51Cr-cytotoxic assay was performed for which PBL were used as effector cells. A LAK activity of 26.6% was observed in PBL cultured with IL2 for 4 days, whereas OK-432-induced LAK activity was 22%. Furthermore, in the in vivo experiment, the anti-tumor effect of LAK cells was evaluated in human bladder tumor transplanted into nude mouse. IL2, OK432-induced LAK cells were injected intratumorally. In the LAK-treated group, inhibition of tumor growth was seen. Histologically, it was demonstrated that infiltrating lymphocytes were scattered around tumor cells. The augmentation of NK activity in spleen cells was observed in the LAK-treated group. Although further studies are required to establish its full significance, these findings suggest that immunotherapy against bladder tumors is hopeful.

Animals↗

[Significance of ultrasonography in detecting renal cell carcinoma].

Eighty-one cases of renal cell carcinoma in last twelve years (1975-1987) have been reviewed and examinations contributing to initial diagnosis of renal cell carcinoma were studied retrospectively. In earlier 5 years from 1975 to 1980, ultrasonography less contributed to detection of renal cell carcinoma than computed tomography. Conversely in the last 3 years from 1984 to 1987, the number of cases were detected by ultrasonography. Since ultrasonography is useful diagnosing renal cell carcinoma of various growth patterns and can detect small space occupying lesions, recently ultrasonography has become a routine examination, and a chance of detecting incidental renal cell carcinoma has been increasing. Ultrasonography should be made at first for screening of renal cell carcinoma.

Carcinoma, Renal Cell↗