Toyohei Machida

Long-term results of intravesical chemoprophylaxis of superficial bladder cancer: experience of the Japanese Urological Cancer Research Group for Adriamycin.

SummaryLong-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, randomized, controlled trial conducted on primary tumors treated with a long-term instillation regimen that involved control versus intravesical instillations of Adriamycin or mitomycin C given once a week for the first 2 weeks, once every other week for 14 weeks, once a month for 8 months, and once every 3 months for 1 year, for a total of 21 instillations in 2 years. An analysis of the prophylactic effects of such treatment on bladder tumors after TUR has previously been performed, and the results have been published elsewhere. The present study represents a follow-up of the above trial. Of the 671 cases previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were eligible to be followed for tumor progression and survival. A detailed comparison of the background factors between these 158 patients and the other 513 cases revealed no statistically significant difference. Thus, the 158 evaluable cases might reasonably be considered to represent all patients enrolled in the second study, and the results were thought to be reasonable enough to reflect the long-term efficacy of the long-term instillation regimen adopted in this study. The median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of the disease stage and/or grade occurred in 43 of 127 patients who received prophylactic instillations and in 12 of 31 control cases. No significant difference in the incidence of tumor progression was found between the treatment and the control groups. In addition, no difference in survival was observed between the treatment group and the control group. Survival was also compared between patients who showed tumor progression and those who did not. All patients whose tumors did not progress survived, whereas the 7-year survival of those exhibiting tumor progression was <90%.

Staging of Renal Cell Carcinoma by Computed Tomography

To evaluate the efficacy of computed tomography (CT) in the diagnostic workup of renal cell carcinoma, CT findings were correlated with surgical and pathological findings in 40 cases. Fifteen cases without obliteration of perinephric fat or thickening of Gerotas fascia were confined within the renal capsule. Eighteen lesions showing anatomic contact with adjacent organs were either within the renal capsule or Gerotas fascia but never beyond Gerotas fascia. Two cases (Stage II) showed thickening of Gerotas fascia and two cases (Stage IV) showed tumor infiltration into the spleen. Computed tomography was found to be a useful method for the investigation of tumor thrombosis and lymph node metastasis.

Papillary adenocarcinoma of the rete testis. A case report

A papillary adenocarcinoma of the rete testis in a 67‐year‐old man is presented. The tumor was localized in the rete testis, showing no involvement of the adjacent testicular parenchyma or the epididymis. The tumor cells manifested a transition to the normal epithelial cells of the rete testis. The electron microscopic features of this tumor are compared with those of the normal epithelial cells of the rete testis. Cancer 50:134–138, 1982.

The 4th study of prophylactic intravesical chemotherapy with Adriamycin in the treatment of superficial bladder cancer: the experience of the Japanese urological cancer research group of Adriamycin

SummaryA multicentric randomised trial was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancer. A total of 443 patients (number of evaluable patients, 284) were registered from July 1987 to December 1989 and randomised into 3 groups. Group A received 21 intravesical instillations of Adriamycin (ADM) at 20 mg/40 ml physiological saline for 2 years after undergoing transurethral resection (TUR); group B was given the same dose as group A but received 6 intravesical instillations for 2 weeks before undergoing TUR; and group C served as a control and underwent TUR only. Better prophylactic effects were obtained in group A. The overall non-recurrence rates calculated for groups A and B differed significantly (P<0.05) on day 240, and those determined for groups A and C were also significantly different (P<0.01) on day 480. No benefit was obtained using intravesical instillation prior to TUR (group B). The major side effects encountered were pollakisuria and miction pain, which occurred in 32% of the patients in group A and in 52% of those in group B.

Operative Nephroscopy With Fiberoptic Scope: Preliminary Report

New fiberoptic scopes, originally designed for biliary tract operations, were used in 23 cases for removal of residual calculi at pyelolithotomy and for examination of the renal pelvis and ureter. The external diameters of the scopes are 6.6 mm. (CHF-X1) and 4.5 mm. (CHF-X2). Water irrigation and forceps manipulation can be performed simultaneously with the CHF-X1 scope but only irrigation can be done with the CHF-X2 scope. The scopes were reliable and allowed easy endoscopic forceps manipulation. Improvements for an ideal fibroptic nephroscope are discussed.

Alterations of gluconeogenesis by ischemic renal injury in rats.

This study was designed to determine changes in one metabolic function, gluconeogenesis (GLG), after ischemic renal injury. Tubule suspensions were prepared by collagenase treatment of SD rat kidneys on 1, 3, and 7 days after left renal artery and vein occlusion for 0-90 min and incubated in Krebs-Henseleit buffer with or without 2 mM pyruvate or malate aerobically. Glucose contents were assayed photometrically. On days 1 and 3 after ischemia for longer than 60 min, serum creatinine levels rose significantly. The tendency of increase of GLG was observed on days 1 and 3 after 10-60 min of ischemia. GLG increased significantly on day 1 after 30-min ischemia. On the other hand, GLG decreased significantly on day 1 after 90-min treatment. Morphologic damage was limited to the corticomedullary region on days 1 and 3 after ischemic times of 30 and 60 min. These results suggest that renal GLG is stimulated to supply energy for ATP decrease by ischemia and for further regeneration in extraproximal segments along the nephron.

Evaluation of systemic chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin for advanced bladder cancer*

SummaryIn a cooperative study of the Japanese Urological Cancer Research Group for Adriamycin, the usefulness of chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC therapy) in treating advanced or recurrent bladder cancer was examined. Evaluation of the clinical responses obtained in 86 evaluable patients revealed 13 complete responses, 29 partial responses, 4 minor responses, 19 cases of no change, and 21 cases of progressive disease. The overall response rate was 48.8% (42/86). The rate of response to M-VAC therapy at each disease site was as low as 21.4% (3/14) in bone lesions but exceeded 40% in the primary lesion, the lymph nodes, the lung, the liver, and other lesions. The clinical response to M-VAC therapy was not significantly influenced by the performance status of the patients, the dose intensity, or previous therapy. The median duration of response for the 42 responders was 22.7 weeks (range, 8.1–134.1 weeks), and the median duration of survival for the 86 evaluable patients was 9.8 months. Side effects were frequently encountered; the patients experienced anorexia, nausea, vomiting, malaise, alopecia, and leukopenia, but all of these symptoms were tolerable.

Phase III trial of The Japanese Urological Cancer Research Group for Adriamycin: cyclophosphamide, adriamycin and cisplatinum versus cyclophosphamide, adriamycin and 5-fluorouracil in patients with advanced transitional cell carcinoma of the urinary bladder

SummaryA non-randomized clinical study on systemic combination chemotherapy was conducted by the Japanese Urological Cancer Research Group for Adriamycin to compare the effectiveness of CAP (cyclophosphamide 200–500 mg/m2, adriamycin 30–50 mg/m2 and cisplatin 30–50 mg/m2) and CAF (cyclophosphamide 200–500 mg/m2, adriamycin 30–50 mg/m2 and 5-fluorouracil 250 mg/m2) in 123 patients (104 evaluable) with advanced and/or metastatic cancer of the urinary bladder. Among 96 patients who were non-randomly selected to receive CAP, 4 achieved complete remission, 12 achieved partial remission, 7 achieved minor response, 30 had stable disease, and 43 had disease progression. The response in the 8 patients who received CAF were: partial remission in 1 and progressive disease in 7. The overall response rate to CAP therapy was 17%, as against 13% for CAF therapy. The median duration of survival with CAP was 29 weeks and with CAF, 22 weeks. The differences between the two groups in duration of survival and response rate were not statistically significant. Complete and/or partial remissions were observed in the lymph nodes, lung and liver in 32%, 24%, and 57% of cases, respectively. There was no objective response in bone metastasis. The main side effects of CAP were anorexia (88%), nausea and/or vomiting (81%), alopecia (65%), leukopenia (72%), anemia (48%), and renal dysfunction (17%). No patients died as a result of toxicity of these combination chemotherapy modalities.

Influence of differences in tumor vascularity upon the effects of hyperthermia

SummaryUtilizing two types of human renal carcinoma heterotransplanted in nude mice, we investigated the variations in hyperthermic effects (42.5°C for 30 min) caused by differences in tumor type with special reference to variations in tumor vascularity. In the hypovascular JRC1 strain, sporadic vascular dilation was observed throughout the tumors after heating. Destruction of tumor cells was observed mainly in the region of dilation. In the hypervascular JRC11 strain, homogenous vascular dilation was observed immediately after heating, mainly at the periphery of tumors. There was a decrease in the viability of cells in the center of the tumor. Therefore, the hypervascular tumors showed greater destruction mainly at the center where blood circulation was reduced. The range of necrosis was also greatly affected by the extent of vascular dilation caused by heating in hypovascular tumors.

Characterization of a Human Chorionic Gonadotropin-Producing Testicular Choriocarcinoma Cell Line

A testicular choriocarcinoma cell line designated JHTK-1 was established in vitro from a mixed germ cell tumor xenografted into nude mice, and may prove to be the first human choriocarcinoma cell line of testicular origin in long-term culture. The cells have been kept in culture for three years and produce human chorionic gonadotropin persistently. The chromosome number distribution ranged from tetraploidy to septaploidy, and trypsin G-band karyotyping showed that all the chromosomes were of human origin. Dibutyryl cyclic adenosine monophosphate at a concentration of 1 mM caused more than 15-fold stimulation of human chorionic gonadotropin secretion with morphological alteration in JHTK-1 cells. This suggests that dibutyryl cyclic adenosine monophosphate induces the differentiation of cytotrophoblastic cells into syncytiotrophoblastic cells among JHTK-1 cells. When JHTK-1 cells were heterotransplanted into the subcutis of BALB/c nude mice, large cystic tumors were produced with histological characteristics similar to choriocarcinoma.