Masayuki Yokokawa

In Vivo Staining Test with Methylene Blue for Bladder Cancer

An in vivo staining test with 0.2 per cent methylene blue was applied to 129 patients with bladder tumor and 16 patients with chronic cystitis within a 6-year interval. Although normal mucosa did not pick up the stain nonpapillary in situ and microinvasive carcinomas did so frequently. Moderate dysplasia was stained in about half of the patients. The intensity of the stain in papillary tumors was correlated with the histologic anaplasia (grade). Grade 1 tumors were stained poorly or unstained in 86 per cent of the tests, whereas grades 2 and 3 tumors picked up the stain in 74 and 96 per cent of the tests, respectively. Even a tiny tumor, if poorly differentiated, was identified easily by the blue stain. The histologic anaplasia of tumors could be assessed roughly according to the intensity of the stain. However, chronic cystitis occasionally took up the stain, especially in cases of marked inflammatory infiltrate a deep stain was recognized. To differentiate nonpapillary early cancer from chronic cystitis the addition of a cytologic examination may be necessary.

Intravesical Mitomycin C and Doxorubicin Sequential Therapy for Carcinoma in Situ of the Bladder: A Longer Followup Result

A total of 43 patients with carcinoma in situ of the bladder (primary in 26 and secondary in 17) who underwent intravesical mitomycin C and doxorubicin sequential therapy for 2 multicenter studies were followed for a median period of 45 months (range 10 to 84). Of the patients 32 (74%) achieved complete response after induction therapy and underwent maintenance therapy with either mitomycin C plus doxorubicin, mitomycin C alone or observation only. Of the complete responders 13 (41%) had a local recurrence, and subsequent repeat intravesical mitomycin C and doxorubicin sequential therapy as well as bacillus Calmette-Guerin was effective in a significant proportion (75% or greater). The maintenance therapy did not have a favorable effect on the recurrence rate. In 8 patients (19%) (3 of 32 complete responders and 5 of 11 nonresponders) progression developed, including invasive cancers in 4, metastatic disease in 2 and both conditions in 2. Initial complete responders had a significantly higher progression-free rate than initial nonresponders, although there was no difference in the sites of progression between them. At the last followup 35 patients (81%) remained free of disease with 31 (72%) having a normally functioning bladder. According to these results, intravesical mitomycin C and doxorubicin sequential therapy appears to be applicable as initial treatment for carcinoma in situ of the bladder.

Carcinoma in situ of the urinary bladder. Effect of associated neoplastic lesions on clinical course and treatment

Clinical courses of 67 patients with carcinoma in situ (CIS) of the urinary bladder bladder during 14 years from 1971 to 1984 were investigated according to the clinical type of CIS and treatment methods. CIS was classified into four types: (1) the primary group included 18 patients who had neither prior nor simultaneous tumors of the urinary tract; (2) the secondary group included 10 patients who had CIS diagnosed subsequent to the treatment of superficial papillary bladder tumor; (3) the concurrent group included 14 patients who had CIS concomitantly with superficial papillary bladder tumor; and (4) the nonpapillary T1 group included 25 patients who presented with CIS with concomitant nonpapillary T1 tumor. As a rule, the initial treatment was conservative (transurethral resection [TUR] or intravesical chemotherapy) for the primary, secondary, and concurrent CIS groups, whereas treatment was radical (total cystectomy or irradiation) for the nonpapillary T1 group. Five‐year survival rates of the primary, secondary, concurrent, and nonpapillary T1 groups were 41%, 100%, 49%, and 68%, respectively. Secondary CIS revealed a rather good prognosis, probably due to the early detection of CIS and early application of intravesical chemotherapy when compared to other groups. Except for patients with nonpapillary T1 tumors, the 5‐year rate of malignant progression (invasion or metastasis) and multiple recurrences leading to delayed cystectomy was 81% in 16 patients treated by TUR, whereas it was 39% in 21 patients treated by instillation therapy. It appears likely that intravesical chemotherapy was preferrable to other conservative therapies as an initial treatment of CIS. Radical therapy, however, may be the choice for CIS with nonpapillary T1 tumors, ab initio. Cancer 59:164–173, 1987.

Intravesical Combination Chemotherapy with Mitomycin C and Doxorubicin for Carcinoma in Situ of the Bladder

We treated 30 patients with carcinoma in situ of the bladder via intravesical combination chemotherapy. As an induction therapy 20 mg. mitomycin C on day 1 and 40 mg. doxorubicin on day 2 were instilled into the bladder once a week for 5 consecutive weeks. Patients who achieved complete response were assigned a maintenance instillation of mitomycin C alone every 2 to 4 weeks for 1 year. A total of 19 patients achieved complete response following an initial course of induction therapy and 2 partial responders to initial therapy also achieved complete response after repeated induction therapy, resulting in a 70 per cent over-all complete response rate. Toxicity was considerable with moderate to severe bladder irritation occurring in 20 patients but it was tolerable in the majority. Of 21 complete responses 13 remained free of disease for 6 to 43 months (average of 23 months), 5 had recurrent carcinoma in situ and 1 had invasive urethral cancer. In contrast, of 9 nonresponders 2 and 1 had invasive cancer of the bladder and ureter, respectively.

Changing expression of ABH blood group and cryptic T‐antigens of noninvasive and superficially invasive papillary transitional cell carcinoma of the bladder from initial occurrence to malignant progression

Thirteen patients who developed malignant progression after frequent recurrence of noninvasive or superficially invasive (Ta or T1) papillary transitional cell carcinoma of the bladder were studied for expression of ABH‐antigens in tumor tissues throughout their clinical courses and cryptic Thomsen‐Friedenreich antigen (T‐Ag) expression in the tumor tissues was examined simultaneously in nine of them. Five patients who experienced recurrent bladder tumors for more than 5 years without any malignant progression were served as control. ABH‐antigens in initial tumors were negative in only two of 13 patients developing malignant progression and in two of five controls. Cryptic T‐Ag was positive in all patients examined. Recurrent tumors revealed eliminated or decreased expression of ABH‐antigens and cryptic T‐Ag before malignant progression in, respectively, ten of 11 and six of nine patients with antigen‐positive initial tumors. In contrast, recurrent tumor of controls with antigen‐positive initial tumors showed neither elimination nor decrease in expression of antigens throughout their clinical courses.

Changes in lanthanum permeability of rat Sertoli cell tight junction after CDDP administration

Using electron microscope, distribution of lanthanum tracer in the seminiferous epithelium was evaluated in adult male rats 2, 7, 25 and 53 days after single intraperitoneal injection of 3 mg/kg of CDDP. Lanthanum penetrated beyond the tight junction between Sertoli cells and the maximum penetration around the spermatid was found on the 7th day, when any degenerative changes of seminiferous epithelium were not recognized light microscopically. And 4 weeks pretreatment with Cephalantin and Kallikulein had no effects on this lanthanum tracer penetration around the spermatid. On decreasing this lanthanum tracer penetration after 7 days, some lanthanum was also found around the spermatocytes on the 53rd day but not around the spermatid. It is proposed that lanthanum tracer penetration beyond the Sertoli cell tight junction may be a morphological marker of early Sertoli cell dysfunction after CDDP administration.

A Study of Prognosis and Clinicopathology of Bladder Cancer to Blood Group Type of Host Patients in Japan

A total of 538 patients with transitional cell carcinoma of the bladder with a mean follow up period of 5.8 years (range 1-25) were retrospectively analysed to see if there were any associations between blood group and grade, stage, or prognosis of the tumour. In contrast to previous findings among European and Americans, there were no significant differences among blood groups for stage, histological grade, or survival rate.

Platelet size distribution as a parameter for evaluating the biocompatibility of dialyzer membranes

目的: 血小板と透析膜の接触から血小板粒度分布を測定し, 意義について検討した.方法: 1) in vitro健常人男性9名より採血を行い全血1mlに対しheparin 17単位を加えplatelet rich plasma (PRP) を得た. 採取したPRPを3μM ADPと接触させ, 接触前後の血小板粒度分布を測定した. また, Cuprophane, EVALの中空糸膜接触前後の血小板粒度分布を同様に測定した. 2) in vitro Cuprophane, EVAL, PMMAの各膜によるdialyzerで9名の透析患者を対象に血小板粒度分布を測定した. 採血は透析開始5分後にdialyzer出入口より行った. 検討した血小板粒度分布の範囲は0-56.6μ3の領域で行い, 血小板の測定にはCoulter Counterを使用した. 結果: 1) ADP接触前後の血小板粒度分布はADP接触前に比べ接触後5.66-11.32μ3間の領域で減少を, 16.98μ3以上の領域で粒子の増加を認めた. Cuprophane膜中空糸では, 接触前に比し接触後5.66-11.32μ3間の領域で減少を, 16.98μ3以上の領域で粒子の増加を認めた. EVAL膜中空糸では16.98μ3以上の領域で粒子の増加を認めたのみであった. 2) 慢性透析患者にCuprophane, EVAL, PMMAの各膜dialyzerを使用し血小板粒度分布を測定した結果, Cuprophane膜dialyzerの出入口では粒子の小さな領域の減少と, 粒子の大きな領域の増加がdialyzer入口側に比し出入口側で認められ, EVAL, PMMA膜dialyzerではdiaiyer出入口での変化を認めなかった.結語: Cuprophane膜中空糸に接触した血小板粒度分布では5.66-11.32μ3間の領域で減少を, 16.98μ3以上の領域で粒子の増加を認めた. これは血小板がCuprophane膜との接触により活性化され, いくつかの凝集塊を形成した結果と考えられる. EVAL膜中空糸の接触前後ではCuprophane膜中空糸に比べその変化は少なかった. Cuprophane膜dialyzerで血小板粒度分布に変化が認められ, 合成膜ではこれが観察されなかったことより, 各膜の性状による血小板への反応性の相違が考えられた. 以上より, 血小板粒度分布測定は透析膜を含めた人工材料の生体適合性評価に意義あるものと思われた.