Katsusuke Naito

Whole Bladder Wall Photoradiation Therapy for Carcinoma in Situ of the Bladder: A Preliminary Report

Whole bladder wall photoradiation therapy, using a hematoporphyrin derivative as a sensitizer, the red light (wavelength 630 plus or minus 1.6 nm.) of an argon dye laser as the source of excitation energy and a motor driven laser light scattering optic, was performed in 2 patients with multicentric carcinoma in situ of the bladder. The total light dose was 10 J. per cm.2. Acute vesical inflammatory changes developed in the bladder wall lining, associated with a reduction of bladder capacity, which, however, disappeared within 3 months after photoradiation therapy. The anticancer effect of photoradiation therapy was followed by urinary cytologic and cystoscopic examinations for 4 months. Occasional discharges of clusters of vacuolated cancer cells or sheets of vesical detached cells in the urine were observed for 2 weeks after photoradiation therapy but, thereafter, repeat urinary cytologic and cystoscopic examinations revealed no malignancy.

Integral Laser Photodynamic Treatment of Refractory Multifocal Bladder Tumors

Integral photodynamic therapy with hematoporphyrin derivative was performed on 35 patients who had resistant transitional cell carcinoma of the bladder, mainly carcinoma in situ. The light source was an argon ion pumped dye laser (wavelength 630 nm.) using rhodamine B. Two types of laser light scattering diffuser developed at our department were used: a motor driven laser light scattering diffuser with computer regulation, and an endoscope modified light scattering diffuser tipped with a small quartz bulb containing a lipid nutritious solution as the scattering medium. The total energy density used was 10 to 30 J./cm.2. Of the 35 patients 24 (68.6%) achieved a complete response and 5 (14.3%) a partial response at 3 months. In 10 of the 24 patients there was no recurrence with an average tumor-free interval of 20.9 +/- 16.7 months, ranging from 5 to 60 months. Bladder capacity was decreased to approximately 150 ml. for 3 months after the integral photodynamic therapy without any evidence of hydronephrosis on excretory urograms, except for 2 patients who had a contracted bladder before photodynamic therapy. Integral photodynamic therapy may prove to be useful for the treatment of carcinoma in situ of the bladder.

Urokinase inhibitor in patients with bladder cancer

SummaryPlasma and tissue inhibitory activities were measured by the fibrin plate method in 33 plasma samples and 25 cancerous tissue specimens from 48 patients with bladder cancer, and were compared with those of normal plasma and bladder tissues, respectively. Both the inhibitory activities were significantly higher in the patients than in normal subjects. In addition, they were significantly higher in patients with cancer of high grades (Grades 2, 3 and 4) and high stages (Stages B, C and D) than in those with cancer of low grade (Grade 1) and low stage (Stage A), respectively. A significant decrease of plasma urokinase inhibitory activity was observed in blood samples obtained 3 weeks after surgical excision of the tumor as compared with that measured before the operation. The physiologic and clinical significances of these findings are discussed.

The Role of Alkaline Phosphatase Isoenzymes as Tumor Markers for Testicular Germ Cell Tumors

The role of serum alkaline phosphatase as a tumor marker for testicular germ cell disease was investigated in 26 patients with testicular seminoma and 13 with nonseminomatous germ cell testis tumors. Placental alkaline phosphatase-like enzyme was elevated in 50% of the stage I seminoma patients and in all patients with stages II to III disease. In addition, liver (tissue unspecific) alkaline phosphatase was elevated in 10 and 83% of the patients, respectively. Lactic dehydrogenase and beta-human chorionic gonadotropin (beta-HCG) were detected in 50 to 60% of the patients with stage I seminoma. By combining placental alkaline phosphatase-like enzyme, lactic dehydrogenase and beta-HCG, 75% of the stage I and 100% of the stages II and III seminoma patients could be identified correctly. Placental alkaline phosphatase-like enzyme in serum also occurred with nonseminomatous germ cell tumor but less frequently, while liver alkaline phosphatase was not detected at all. Thus, placental alkaline phosphatase-like enzyme and liver alkaline phosphatase were predominantly determined in the serum of patients with seminoma. In studies of tumor tissues from 31 of these patients, those with normal serum placental alkaline phosphatase-like enzyme levels had significantly lower tissue placental alkaline phosphatase-like enzyme levels than patients with elevated serum levels (p less than 0.01). Seminoma tissues showed significantly higher levels of placental alkaline phosphatase-like enzyme and liver alkaline phosphatase than nonseminomatous germ cell tumors (p less than 0.01), explaining the infrequent elevation of serum placental alkaline phosphatase-like enzyme and liver alkaline phosphatase found in patients with nonseminomatous germ cell tumors.

The prophylactic use of thio-tepa and urokinase in transitional cell carcinoma of the bladder: a preliminary report.

The prevention of recurrences of bladder cancer was attemped in 48 patients by means of the combined intravesical instillation of thio-tepa and urokinase and in 28 patients through the instillation of thio-tepa alone. The recurrence rates of both therapies for the postoperative 18 months were 7.9 and 32.6 per cent, respectively, indicating a significant drop in the recurrence rate in the group subjected to the combined therapy. No significant difference was found between the 2 instillation groups in terms of the blood transmission of 32-P thio-tepa. Serious leukopenia was found in 2 of the 48 patients receiving the combined instillation therapy but we concluded that this was not attributable to the use of urokinase.

Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced urothelial cancer

SummaryA series of 31 patients with advanced urothelial cancer were treated with combination chemotherapy consisting of 1–4 cycles of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC). Of the 31 patients, 29 had measurable and evaluable lesions. A complete remission was achieved by 4 of these 29 patients (14%) for 1–46 months. A partial remission was observed in 14 of the 29 patients (48%) for 1–9 months. Whereas bony and hepatic metastatic lesions did not respond, some nodal (7/12), pulmonary (4/8), and pelvic lesions (2/3) as well as primary bladder tumors (4/6) and a tumor marker (1/2) responded. Complete tumor remission was observed in nodal (2/12) and pulmonary (1/8) metastatic lesions, in invasive lesions to the prostate and seminal vesicle (1/1), and in primary lesions in the bladder (2/6), ureter (1/1), and urethra (1/1). Two of three patients with non-transitional cell tumors attained a partial remission for 1–7 months. Complete remission of the pulmonary lesions was obtained in a case of squamous cell cancer of the bladder with pulmonary metastases. The toxicity of this regimen was generally tolerable and included moderate to severe myelosuppression, mild to moderate nausea and vomiting, renal toxicity, and mucositis. These results suggest that the M-VAC regimen holds promise for the treatment of advanced metastatic transitional cell cancer as well as nontransitional cell cancer of the urothelium.

Percutaneous Mitomycin C Perfusion of Bilateral Ureteral Carcinoma in situ

We treated a 61-year-old patient with a diagnosis of bilateral ureteral carcinoma in situ with percutaneous perfusions of mitomycin C. After 16 sessions of mitomycin C therapy instilled through bilateral nephrostomy tubes, the urine cytology results became negative for malignancy. Bilateral ureteroscopy and cold-cup punch biopsies of the ureter revealed no evidence of disease. The patient did not experience side effects. He has remained free of disease during a 12-month follow-up period. Percutaneous perfusion of mitomycin C appears to be one of the effective and safe treatments for the carcinoma in situ of the upper urinary tract.

Photodynamic therapy with a various of phthalocyanines in tumor transplanted nude mice

Using nude mice bearing transplanted tumor of a KK-47 human bladder cancer, the effects of photodynamic therapy(PDT) with Al-phthalocyanine (AlPC), In-phthalocyanine(InPC) and Ga-phthalocyanine(GaPC) were compared. Photodynamic effects were evaluated as the tumor growth curves. For tumor control, the following efficies were found: AlPC) InPC)-GaPC. And PDT effect with AlPC and laser light at 670nm were compared with that ofAlPC and laser light at 630nm, and that of hematoporphyrin derivative(HpD) and laser light at 630nm. The regression of tumor volume after PDT was more with AlPC and laser light at 670nm than with A1PC and laser light at 630nm, and with HpD and laser light at 630nm. These results suggest that AlPC may be promicing photosensitizer for PDT in respect of the tumor destruction.