カルボコンの膀胱腔内注入により生じた局所的副作用について

Abstract

One case of contracted bladder and 2 cases of remarkable decrease of bladder capacity by intracavitary instillation of carboquone (CQ) were presented. The instillation was performed against bladder cancer. Case 1: A 69 year-old-male visited the Dept. of Urol., Nagoya City University Hospital, complaining of miction pain. Cystoscopic examination revealed solid and sessile tumors on the bladder neck. Bladder capacity was 300 ml. Histologic diagnosis was transitional cell carcinoma, grade 3. 5 mg of CQ was dissolved in 10 ml of distilled water and instilled into the bladder, 3 times a week. After 13 times of instillation, urinary frequency appeared. Since it became severe at 17 times (total dose: 85 mg), instillation was discontinued. Cystoscopy showed 50 ml of capacity and pale appearance of the mucosa. The muscle layer was exposed at the upper region of right side wall. The tumors disappeared, apparently. As bladder capacity did not increase 4 weeks after discontinuation of instillation, total cystectomy and bilateral ureterosigmoidostomy were performed. Histologic examination of the extirpated bladder disclosed degeneration, necrosis and denudation of the mucosa and fibrosis in the muscular layer. Case 2: A 55 year-old-male visited the Dept. of Urol., Nagoya Municipal Josai Hospital, because of gross hematuria. Cystoscopy revealed a walnut-sized, papillary and half-pedicled tumor in the neck and on the trigone, respectively. Capacity was 300 ml. Biopsy specimens showed transitional cell carcinoma, grade 2. Instillation of CQ 5mgJdistilled water 10ml was performed 4 times a week. Because the tumors did not become smaller by 12 times of instillation, dose of CQ was increased to 10mg/l5ml. As CQ was not effective in spite of total dose of 170mg, the treatment was interrupted. Since then frequency of urination began to increase and reached 24 times a day. By conservative therapy it improved 2 weeks after discontinuation of instillation. Case 3: A 74 year-old-female came to the Dept. of Urol., Nagoya First Red Cross Hospital with the chief complaint of hematuria. By cystoscopy, capacity was about 200ml and a thumb's headsized, papillary and pedunculated tumor was demonstrated just above the right ureteral orifice. Biopsy specimens histologically showed transitional cell carcinoma, grade 1-2. 5mg of CQ was dissolved in 20ml of saline and instilled into the bladder, 3 times a week. After 14 times, size of the tumor reduced slightly, however, severe frequency (40 times a day) appeared. The treatment was interrupted and intravesical instillation of betamethasone was begun. Intramuscular injection of dexamethasone was also started. After 10 days' administration of both steroids, frequency improved and then TUR-Bt was performed. Discussion: Cyclophosphamide, which is one of the alkylating agents, has occasionally produced hemorrhagic cystitis and shrunken bladder. After systemic administration, cyclophosphamide is changed to active form by phosphatase and phosphamidase. It is excreted by the kidney and affect the bladder. Its effect is enhanced by phosphatase in the bladder wall. Carboquone is also one of the alkylating agents and thought to have similar effect as cyclophosphamide on the bladder epithelium in specific conditions. Since molecular weight of CQ is 321.34, according to the theory of Yeates, it does not seem to pass the bladder epithelium in normal condition. Therefore, local side effects by CQ may be due to its direct action to the bladder. To prevent local side effects seen in instillation of CQ the following consideration is advocated. 1) Concentration of solution of CQ should be settled under 250mcg/ml. 2) Instillation should be interrupted when frequency of urination exceeds 20 times a day (frequency often appear when total dose of CQ reaches 50 mg). 3) Complete disappearance of tumor should not be expected if the diameter of tumor exceeds 1cm. 4) Combination of instillation of steroids with CQ may reduce the side effects. 5) Hydration may also reduce the side effects, however, it should be kept in mind that frequency of urination will increase by hydration. 6) Procedures to intensify the effect of CQ (e.g., dehydration, increase of concentration of the drug, control of urination, etc.) may augment the side effects. As one of the treatments of severe bladder damage by CQ systemic and local administration of steroids is recommended after interruption of instillation. If contracted bladder resulted palliative therapy wiII be unsuccessful.