Search

Background: Intravesical Bacillus Calmette-Guérin (BCG) is now a standard treatment for Ta, T1 carcinoma and carcinoma in situ (CIS) of the urinary bladder. In Japan, however, only BCG Tokyo 172 strain is commercially available. We therefore designed a clinical study of PMCJ-9 (BCG Connaught strain) for obtaining approval from Japanese Ministry of Health, Labor and Welfare., Methods: In the phase I-II study, PMCJ-9 40.5, 81 (standard dose overseas) or 121.5 mg in saline was instilled into the bladder of patients with Ta, T1 or CIS once weekly for 8 weeks. The recommended dose was decided and similarly administered in the late phase II study., Results: In the phase I-II study, 49 patients were evaluable for efficacy. The complete response (CR) rates were 60.0% (9/15), 68.2% (15/22) and 75.0% (9/12) in the 40.5, 81 and 121.5 mg groups. The incidence of adverse drug reactions (ADRs) was similar in all groups, but four 121.5 mg group patients developed severe ADRs. Thus, 81 mg was the recommended dose for the late phase II study. In that study, 39 patients were evaluable, showing CR rates of 71.8% (28/39) overall and 61.5% (16/26) and 92.3% (12/13) for the Ta, T1 and CIS cases. The safety was assessed in 42 patients and three (7.1%) were discontinued owing to ADRs., Conclusion: The recommended dose for the BCG Connaught strain was decided as 81 mg. PMCJ-9 administration at this dose level weekly for 8 weeks showed a clear antitumor effect and good safety profile against Ta, T1 and CIS transitional cell carcinoma of the bladder.

Objective: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade., Methods: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate)., Results: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone., Conclusions: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Background: Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed., Methods: CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion., Results: Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P < 0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P < 0.0001)., Conclusion: A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy.

Between July 1991 and December 1994 at Tsukuba Gakuen Hospital, we treated 19 consecutive men with advanced adenocarcinoma of the prostate (five at stage C, four at stage D1 and 10 at stage D2). Of these, 14 patients underwent castration (two patients) or received LH-RH analogue (12 patients) plus chlormadinone acetate for combined androgen blockade. We report three representative cases of sequential prostate specific antigen (PSA) elevation following initial response to this combined androgen blockade. Discontinuation of chlormadinone acetate resulted in decline of the serum PSA level. This suggests that trial chlormadinone acetate withdrawal in patients showing increasing levels of PSA during combined androgen blockade should be considered before initiation of alternative treatment.

We have conducted a double-blind comparative study of flutamide and chlormadinone acetate (CMA) on patients with stage C or D prostatic cancer and with no prior experience of hormone therapy. This is believed to be the first such trial entered in the medical literature, fifty-four patients were randomly selected to undergo flutamide (p.o.) monotherapy at a daily dose of 375 mg, which was determined as the optimal dose in Japan in our previous phase II study. Forty-nine others were randomly selected to undergo CMA (p.o.) monotherapy at a daily dose of 100 mg, which is the most commonly used dosage in Japan for patients with prostatic cancer. Ultimately, 47 patients from the flutamide group and 40 patients from the CMA group were judged eligible, with efficacy being evaluated after 12 weeks of treatment. Similar objective responses were seen in both groups: 48.9% (95% confidence limits 34.1-63.9%) in the flutamide group, 45% (95% confidence limits 29.3-61.5%) in the CMA group. The response at each organ site was also similar between the groups. Serum prostatic specific antigen decreased by more than 50% of the abnormal pretreatment level in 87.5% of the flutamide group and in 85.7% of the CMA group. Serum luteinizing hormone, follicle-stimulating hormone, testosterone and 5 alpha-dihydrotestosterone decreased significantly in the CMA group, but increased significantly in the flutamide group. The serum testosterone level after 12 weeks of treatment was 0.955 +/- 0.13 ng/ml in the CMA group and 6.64 +/- 0.38 ng/ml in the flutamide group. The serum estradiol level also increased significantly in patients in the flutamide group. The serum prolactin level decreased significantly in the flutamide group, but increased significantly in the CMA group. Eight patients on flutamide manifested gynecomastia. Diarrhea and hepatic toxicity were observed in both groups, but only rarely, and were well tolerated. We have thus concluded that flutamide is as effective as CMA in maintaining libido and potency without decreasing testosterone levels.

To avoid confusion between serum prostate-specific antigen (PSA) values among various assay systems, clinical studies on the possibility of conversion among detection values were performed. The assay kits used for the PSA comparisons were MARKIT-F PA, MARKIT-M PA, EIKEN PA, PA test WAKO, Ball ELSA PSA, E-Test Tosoh II PA, PROS-CHECK PSA, DELFIA PSA and TANDEM-R PSA. Using each kit, the standards attached to each assay system were detected, and 142 sera samples from benign hypertrophies or prostate cancers were assayed for serum PSA values. By detecting the standards for each kit, slopes were obtained which were almost identical to those obtained from original assay system. The coefficients of correlation among the PSA detection systems, using patients' sera, were very high, and linear regression lines were also obtained. The results suggest that almost identical serum PSA values may be detected either by multiplying by a coefficient to bring it to the standard or using the conversion formula.

The results of long-term administration of leuprorelin acetate depot (TAP-144-SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH-RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer.

The present paper reports the clinical results from cases of renal cell carcinoma with vena caval tumor thrombus. Fifty patients were entered into the study between 1980 and 1989. The primary tumor and vena caval tumor thrombus were completely removed in 39 (78%) patients, and 41 (82%) received postoperative treatment. The overall 12-, 36-, 60- and 90-month actuarial survival rates were 72, 41, 19 and 10%, respectively. Only tumor stage affected survival, however, other factors such as tumor grade, nodal status, metastatic status and level of vena caval involvement not affecting it. Postoperative interferon (IFN) treatment affected survival, whereas degree of curative surgery did not. The results of our study were, however, examined retrospectively in several institutes. Further investigation of the postoperative treatment for renal cell carcinoma with vena caval tumor thrombus will be necessary.

Renal cell carcinoma is the third most frequent cause of urological cancer death in Japan. The first is bladder cancer and the second is prostatic cancer. However, there has been no clinical trial of mass screening for early detection of renal cell carcinoma. With a view to discovering a method of early detection for renal cell carcinoma, we analyzed the procedures for discovering renal cell carcinoma in 33 patients who were treated at our hospital. In 10 patients, carcinoma had been discovered accidentally without gross hematuria, abdominal mass or flank pain. Seven of these patients were first suspected of having renal cell carcinoma by ultrasonography, two by intravenous pyelography (IVP) and one by computed tomography. Seven out of nine patients operated on were surgically diagnosed as having stage I and two as having stage II. Ultrasonography is far better than IVP from the points of view of noninvasiveness, ease of performance and accuracy. In our study, ultrasonography was the most useful method for early detection of renal cell carcinoma. However, for the mass screening of renal cell cancer by ultrasonography, it is necessary to make its specificity and sensitivity clear and to debate its cost effectiveness.

We used 29 polymorphic DNA markers to analyze tumor DNA samples from six patients with sporadic pheochromocytoma for possible loss of chromosomal heterozygosity; four had benign disease and two had malignant disease. Loss of heterozygosity was observed on four chromosomes: 1p (three of four patients), 2p (one of one), 5q (two of six), and 11p (three of five). Chromosomes 1p and 11p frequently had allelic deletions in these tumors, and these deletions may play an important role in the development of pheochromocytoma.

This report presents a case of colonic adenoma which developed after ureterosigmoidostomy. A 71-year-old man was initially treated by total cystectomy and ureterosigmoidostomy for transitional cell carcinoma of the bladder in 1970. In 1983, a routine checkup revealed urinary occult blood. A barium enema x-ray showed a polypoid lesion in the sigmoid colon. Colonoscopy confirmed the presence of the polyp adjacent to the ureteral stoma. The biopsy findings were interpreted as villous adenoma with severe atypia. This tumor was removed endoscopically. This is the seventh case report of neoplasia occurring in the sigmoid colon after ureterosigmoidostomy in Japan. Review of the pertinent literature indicates that patients who have undergone this type of urinary diversion have an increased risk of development of large bowel neoplasia. Adequate and regular surveillance of these patients has been suggested in order to help in early detection.

The clinical aspects of 64 patients with superficial bladder cancer (Ta, T1, T2 according to the TNM classification, International Union against Cancer or Stage O, A, B1 according to Marshall) admitted to the Tsukuba University Hospital were analyzed retrospectively. Treatment of these patients was mainly by transurethral surgery. The overall 10-year survival rate was 73%. Eight patients died and four of them showed an invasive change, the so-called metamorphosis, during the follow-up period. Patients with papillary, pedunculated tumors had better survival rates than those with papillary, sessile tumors. Patients with tumors less than 1 cm in size had better survival rates than those with tumors 1-3 cm in size. There were no statistical differences in survival rates between patients with single and multiple tumors. Up to seven years from surgery, the patients with T2 tumors had lower survival rates than those with Ta-T1 tumors. The patients with grade I tumors had better survival rates than those with grade II tumors. There were no significant differences in recurrence rates related to the grade of the tumor. It is thought that the prognosis of superficial bladder cancer in our series depended mainly on the shape, size, number, depth and grade of the tumor.

A review of 27 patients with renal pelvic tumors and ureteral tumors admitted to the Tsukuba University Hospital was performed retrospectively. Nineteen cases of renal pelvic tumors and eleven cases of ureteral tumors were submitted to the study. These patients were treated mainly by surgery. The rates for 1-year, 3-year, 5-year and 10-year survival were 88.5%, 57.6%, 40.3% and 20.2%, respectively. No obvious relationship between prognosis of renal pelvic tumor and that of ureteral tumors was seen. Pathologically, there was a correlation between the grade and the stage of the tumor. Prognosis was related to the stage of the tumor, but not to the grade of the tumor. Clinically, the patients with positive urinary cytology had a poorer prognosis. It was considered that no relationship existed between the preoperative clinical stage and the postoperative pathological stage. Consequently, the former is not considered a prognostic factor. We have been performing mainly radical nephroureterectomy with regional lymphadenectomy since 1975. The patients who received the operation with regional lymphadenectomy since 1975. The patients who received the operation with regional lymphadenectomy or with adjuvant chemotherapy had a better prognosis. It is concluded that lymphadenectomy is a valuable operation for improving prognosis.

Renal cell carcinoma in a solitary kidney is rather rare. We present a case of this condition occurring in a 50-year-old man. He was treated by partial nephrectomy and temporary hemodialysis for postoperative acute renal failure. Perusal of the literature reveals that in situ partial nephrectomy, if possible, seems to be a reasonable treatment of choice for renal cell carcinoma in a solitary kidney. This is the fifth case ever reported in Japan.

We reviewed 60 cases of incidental carcinoma of the prostate treated conservatively. Subclassification of incidental carcinoma was based on histologic grade and tumor size. Stage A1 was defined as a low grade (grade I) and focal lesion, and stage A2 as a high grade (grade II, III) or diffuse lesion. The distinction between focal and diffuse was set at three chips in a transurethrally resected specimen or a diameter of 5 mm for a total lesion in an enucleated specimen. Patients with stage A1 tumors did significantly better (p less than 0.05) than those with A2, the 5-year survival rates being 88% and 70%, respectively. It is believed that patients with stage A2 should be treated aggressively. However, conservative therapy is recommended for the patients with stage A1 prostate cancer.