[Clinical efficacy and reduction effect on prostatic volume of chlormadinone acetate combined with tamsulosin hydrochloride in benign prostatic hyperplasia patients insufficiently treated with tamsulosin hydrochloride only].

Alpha adrenergic blocker has become the first choice in the medical treatment of benign prostatic hyperplasia (BPH). The efficacy of alpha adrenergic blocker has been suggested to be related to the prostatic tissue components, and to be ineffective in treating the clinical symptoms caused by BPH in some cases. The efficacy and prostate reduction of an anti-androgenic agent, chlormadinone acetate, combined with alpha adrenergic blocker, tamsulosin hydrochloride, were evaluated using 40-BPH patients insufficiently treated with tamsulosin hydrochloride alone. Fifty mg of chlormadinone acetate and 0.2 mg of tamsulosin hydrochloride were administered orally once a day for 16 weeks to patients with a prostate subjective symptoms score, I-PSS, of greater than 13 or a peak flow rate of less than 12 ml/s, even after the treatment with 0.2 mg of tamsulosin hydrochloride alone for more than four weeks. Total I-PSS decreased significantly after four weeks. The total irritative symptom score did not change for 16 weeks, but the total obstructive symptom score decreased significantly, as did the total I-PSS. In objective data, the estimated volume of both total prostate and the transition zone on transrectal ultrasonogram decreased significantly at the end of the treatment, and the peak flow rate decreased significantly after 12 weeks. These findings suggest that the addition of chlormadinone acetate may be a reasonable alternative in the treatment of BPH patients responding insufficiently to tamsulosin hydrochloride alone, and that combination therapy using chlormadinone acetate and tamsulosin hydrochloride may be useful for BPH patients with serious obstructive symptoms.

[Clinical evaluation of tamsulosin hydrochloride on bladder outlet obstruction associated with benign prostatic hyperplasia: effect on urethral pressure profile and cystometrogram].

The efficacy and safety of tamsulosin hydrochloride were evaluated in 54 patients with bladder outlet obstruction associated with benign prostatic hyperplasia. Oral tamsulosin hydrochloride 0.2 mg was administered once daily for 7 weeks. The international prostate symptom score, residual urine, uroflowmetrogram, urethral pressure profile and cystometrogram were obtained before and after treatment. The international prostate symptom score improved significantly, and the residual urine volume and ratio of residual urine decreased significantly. In uroflometry, voided volume, maximum flow rate and average flow rate increased significantly. In urethral pressure profile, prostatic urethral pressure decreased significantly. In cystometry, bladder capacity at the first sensation increased significantly. No adverse reactions except for slight elevation in laboratory data in 3 patients were observed. In conclusion, tamsulosin hydrochloride is a useful drug in the treatment of bladder outlet obstruction associated with benign prostatic hyperplasia.

[Clam ileocystoplasty for neurogenic bladder due to spina bifida].

A 24-year-old female with neurogenic bladder due to spina bifida consulted our department for further evaluation and treatment of a left renal stone. She innately voided urine by Crede's method. At the age of 15 years, intermittent self-catheterization was started because left severe hydronephrosis was found. At the age of 19 years, cystostomy was performed because of low compliance bladder and an aggravation of hydronephrosis in spite of intermittent catheterization. Thereafter, she was referred to our department for further evaluation and treatment of a left renal stone since the stone was increasing in size. First, left percutaneous nephrolithotomy was performed successfully. Secondly, clam ileocystoplasty using the ileum was carried out, followed by 1) increase of the bladder capacity, 2) improvement of the bladder compliance, 3) adequate intermittent self-catheterization, and 4) disappearance of urinous odor resulting from removal of the cystostomy catheter. Thus, the clinical effects were thought to be significant.

The influence of prostatic urethral anesthesia in overactive detrusor in patients with benign prostatic hyperplasia.

We examined the effects of prostatic urethral anesthesia on cystometrography in benign prostatic hyperplasia (BPH) patients with or without neurological disorders. Although cystometrography after anesthesia showed no disappearance of involuntary detrusor contraction, it did demonstrate significant increases in first sensation volume and maximum cystometric capacity in BPH patients without neurological diseases, as well as BPH patients with a history but no physical evidence of neurological disease. Furthermore, the bladder might be augmented more efficaciously in patients with involuntary detrusor contractions. No significant differences were found in first sensation volume or maximum cystometric capacity before and after anesthesia in patients without infravesical obstruction who had documented neurological disease with physical evidence. Our results demonstrated that prostatic urethral anesthesia can be used preoperatively in patients with infravesical obstruction to discriminate whether involuntary detrusor contractions are due to infravesical obstruction or to neurological disease.

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

A 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 non-transitional cell cancer of the urothelium.

[A clinical survey of advanced bladder cancer: treatment of advanced and non-resectable bladder cancer].

Sixty-three patients with advanced cancer of more than T3b and/or non-resectable bladder cancer who were treated at Kanazawa University Hospital from January 1982 to June 1990 were analyzed with regard to treatment and prognosis. Thirty-one of the 63 patients had non-resectable bladder cancer; T3b in 9, T4b in 15, M1 in 6 and N4 in 4. Twenty-four of the 31 patients received anticancer therapy consisting of systemic chemotherapy, 8 MHz-RF hyperthermia, radiation or a combination of these modalities. With this treatment 9 patients achieved partial response, 4 minor response, 7 no change and 2 progressive disease. In 2 patients evaluation was not performed. Seven of the 31 patients received no treatment. One-year and 2-year survival rates with the above types of treatment were 27.7% and 16.7%, respectively, and 33.4% and 16.7%, respectively, without anti-cancer treatment. There was no significant difference between the survival rates of the two groups. Thirty-two of the 63 patients underwent operation. In 17 patients, total cystectomy was carried out, 9 and 8 of whom received and did not received respectively various adjuvant therapies before operation. One-year and 2-year survivals in the group undergoing adjuvant therapy were 33.3% and 11.1%, respectively, and 66.7% and 66.7% respectively in the group without adjuvant therapy. Survival of the 2 groups did not differ significantly. These data indicate that anticancer treatment including chemotherapy, hyperthermia and radiation dose not enhance long-term survival.

[Photodynamic therapy of superficial tumors and carcinoma in situ of the bladder].

Photodynamic therapy (PDT), in which hematoporphyrin derivative is activated by an argon-dye laser, was performed on 36 superficial tumors using a 400 micron quartz fiber and cystoscope (spot PDT), and also carried out in 7 patients with primary or secondary CIS, 9 patients with secondary CIS associated with TaTl tumors and 2 patients with multiple small tumors, using a motor-driven laser light scattering optic automatically controlled by a computer (total PDT). In spot PDT, for tumors up to 2 cm in size the light intensity should be 300 mW/cm2 for 5 to 10 minutes or more. For the CIS therapy, the light dose used was 10 to 30 Joules/cm2. There has been no recurrence at present in 8 of the 18 patients at a mean follow-up period of 6.6 months. The techniques and problems associated with total PDT are reported.

[A hyperthermic perfusion therapy using peplomycin and ethanol for bladder cancer].

Distilled water containing 40 micrograms/ml peplomycin and 2% ethanol was used as a perfusate in 8 patients with superficial bladder tumors and 2 with deep bladder tumors for 2 hours at 43 degrees C. In addition, immediately before the perfusion treatment, 5 mg of peplomycin was injected intramuscularly. Prior to treatment, the nature and extent of the tumors were determined by ultrasonography, cystoscopy and cystography. The therapeutic effect of the hyperthermic perfusion was evaluated by the same manner as used previously. Partial tumor regression was obtained in 6 of the 8 patients with superficial bladder tumors. The 2 patients with deep bladder tumors showed no tumor regression. Most of the patients had bladder discomfort such as irritation, pollakisuria and so on, during and/or after perfusion. No patient developed acute pyelonephritis.

Cellular uptake of hematoporphyrin derivative in KK-47 bladder cancer cells.

The fluorescence emission spectra and degree of fluorescence polarization of hematoporphyrin derivative (HpD) have been investigated using HpD-containing KK-47 cells, PBS and cetyl trimethyl ammonium chloride (CTAC) micellar solutions. The fluorescence emission bands in the HpD-containing cell suspension were red-shifted and broadened as compared to those in the PBS solution. The degree of the polarization in the PBS and CTAC micellar solutions did not change with increasing incubation time, but in the cell suspension it increased temporarily and then decreased 4 h after incubation. These results suggest that HpD monomers and dimers may bind weakly to the outer cell membrane, and then slowly distribute throughout the intracellular loci in strong-binding form. In addition, the cellular uptake and/or binding loci of HpD were considered to be the mitochondria and nuclear membrane by subcellular fractionation and fluorescence microscopic studies.

Cellular binding of hematoporphyrin derivative (HpD) in human bladder cancer cell line: KK-47.

In vitro cellular uptake or binding of hematoporphyrin derivative (HpD) was investigated by comparing the optical properties; absorption spectra, fluorescence spectra, fluorescence lifetime and fluorescence polarization, of HpD in KK-47 cells derived from a human bladder carcinoma, organic and micellar solutions. In addition, the relationship between the mode of cellular HpD uptake and photodynamic cellular inactivation by argon-dye laser was studied using a clonogenic assay system. HpD molecules may weakly bind to the cell membrane within approximately 2 hrs after incubation in HpD-containing medium, and then major HpD molecules may slowly be distributed throughout the cytoplasm as a dimer form for 4 hrs after incubation in HpD-free medium. The intracellular binding loci were found to be the mitochondria and nuclear membrane by subcellular fractionation and fluorescence microscopic studies. The loci may be relatively hydrophilic on the basis of the polarity-dependence data on the fluorescence polarization. An exponential cellular photoinactivation curve was observed in relation to increasing concentrations of HpD and to intracellular strong-binding of dimeric HpD.

[Eosinophilic cystitis: a report of 2 cases].

Two patients with eosinophilic cystitis are presented in this report. The first case was a 39-year-old man who was admitted to our clinic with complaints of pollakisuria, pain on urination and hematuria for a month, which had not been relieved by antibiotic therapy. He had both a family and a personal past history of allergy. Excretory urograms showed a mild bilateral hydroureter and small bladder with irregular filling defects. Cystoscopic examination revealed velvety, ulcerated areas in the bladder mucosa, and we diagnosed these changes as eosinophilic cystitis after bladder biopsy. Steroid and antihistaminic therapy improved these symptoms. The second case was a 67-year-old woman who visited our clinic complaining chiefly of hematuria for 2 months. There was no predisposition to allergy, but she had a past history of uterine cancer which had been treated with irradiation. Cystoscopic examination disclosed a large amount of intravesical coagula, and erythematous and edematous areas with petechiae of the bladder mucosa. Bladder biopsy revealed hemangioma and eosinophilic cystitis. There was no recurrence of cystitis after the removal of the coagula without any other treatment.

Inhibition of cell growth by irradiation in combination with hyperthermia or anticancer drugs.

Using a clonogenic assay and the human bladder cancer cell line T24, enhanced cytotoxicity by the combined use of irradiation and 43 degrees C hyperthermia or two anticancer drugs, bleomycin (BLM) and cis-dichlorodiammineplatinum (CDDP), has been investigated in vitro, as well as the size of colonies derived from single survivor cells after treatment. Irradiation combined with 43 degrees C hyperthermia showed greatly enhanced cytotoxicity and diminution in mean colony diameter and decreased distribution of colony size. BLM had almost the same effect as 43 degrees C hyperthermia in terms of cytotoxicity and colony size. While CDDP showed a certain degree of enhanced cytotoxicity in combination with irradiation, it produced no appreciable decrease in mean colony diameter. Hyperthermia may be beneficial in the management of radiation resistant cells surviving a large dose of radiation, and would seem to be a promising means for achieving eradication of cancer cells in combination with radiation therapy.