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A prospective chemotherapeutic trial using combinations of three drugs consisting of three different protocols was performed in 24 patients with advanced transitional-cell carcinoma of the urothelial tract between April 1981 and August 1986. All patients had histologically proven transitional-cell carcinoma and bidimensionally measurable lesions. The protocol I (PPA) was a 5-day course of treatment with 20 mg/m2 cis-platinum and 5 mg/m2 peplomycin (a derivative of bleomycin) on days 1-5, and 25 mg/m2 adriamycin on day 1. Protocol II (CFMit) was a 10-day course with 3 mg/m2 mitomycin-C and 300 mg/m2 cyclophosphamide on day 1, and 180 mg/m2 5-fluorouracil on days 1-10. Protocol III (PAM) was a 1-day course comprising 60 mg/m2 cis-platinum, 30 mg/m2 adriamycin, and 40 mg/m2 methotrexate. In protocols I and III, the drugs were administered every 4-5 weeks, while in protocol II, the drugs were administered continuously without any interval. Of the 9 patients who received 1 to 5 PPA courses, only 3 patients showed a minor response. In the 10 patients who received 4 to 44 CFMit courses, 3 (33%) achieved partial remission for 1.5-22 months, and 3 had a minor response. Of the 5 patients receiving 3 to 7 PAM courses, 1 patient achieved partial remission for 5 months, and 1 had a minor response. Myelosuppression, nausea, vomiting, and anorexia were frequently observed in each protocol. Loss of hair was often observed in protocols I and III. Stomatitis and diarrhea were observed in protocol II. Three patients in protocol I, 4 patients in protocol II, and 1 patient in protocol III were unable to tolerate more courses of the regimen due to the severe side effects.

During about 10 years from November, 1977 to March, 1987, 46 patients with renal pelvic and ureteral tumors were treated at the Department of Urology, Hamamatsu University School of Medicine and the affiliated hospitals. There were 34 males and 12 females with the highest age incidence in the seventies. Histologically, 44 transitional cell carcinomas and 2 squamous cell carcinomas were found. Of the 44 transitional cell carcinomas, 1 was Tis; 13 T1, 2 T2, 8 T3, 15 M+ (with metastatic lesion), and 5 TX. As to grading, 1 was G1; 24 G2, 15 G3, and 4 GX. Staging was correlated with grading. The 5-year survival rates (Kaplan-Meier's method) were 37% in patients with transitional cell carcinoma. Among patients with transitional cell carcinoma, the 5-year survival rate was 43% for G2 and 42% for G3. As to staging, the 5-year survival rates were 71% and 46% in patients with stage of T1 and T3, respectively. No patient with M+ survived longer than 4 years. The 5-year survival rates were 38% and 34% in renal pelvic tumors (24 cases) and ureteral tumors (20 cases), respectively. As to the treatments, the 5-year survival rates after curable treatment (24 cases) and non-curable treatment (20 cases) were 63% and 7%, respectively.

116 normocalcemic and 8 primary hyperparathyroid (PHPT) patients with calcium (Ca) nephrolithiasis and 10 normal controls underwent 1 g of oral Ca tolerance test following 4 days of Ca restricted diet (400 mg/day). On the basis of urinary Ca/creatinine (Cr) ratio obtained by the test, the 116 patients with normocalcemic nephrolithiasis were divided into 3 groups (normocalciuric nephrolithiasis; NN, absorptive hypercalciuria; AH, renal hypercalciuria; RH) according to our criteria which were slightly modified from Pak et al. Changes in urinary Ca/Cr ratio, and those in serum Ca and phosphorus (P), tubular maximum reabsorption of phosphate/glomerular filtration rate (TmPO4/GFR), nephrogenous adenosine 3',5'-monophosphate (NcAMP) and plasma immunoreactive parathyroid hormone (iPTH) were determined. As a result, the 116 patients were divided into 82NN, 13AH and 21RH. In general, a rise in serum Ca and fall in NcAMP were seen first, followed by rises in urinary Ca/Cr ratio, serum P and TmPO4/GFR although the changes were small. The group PHPT showed abnormality in the changes of TmPO4/GFR, NcAMP and plasma iPTH. The former one decreased constantly during the test and the latter two did not fall to within the normal range, suggesting parathyroid autonomy or abnormal suppressibility. Regarding the normal controls, all the changes were smallest among the 5 groups and clear parathyroid suppression was not observed while it was seen in the groups NN, AH and RH. In conclusion, oral Ca tolerance test is useful not only to separate NN, AH and RH, but also for the diagnosis of PHPT by demonstrating parathyroid autonomy or abnormal suppressibility assessed by NcAMP and/or TmPO4/GFR.

Reaction of mild phosphorylating agents, such as phosphorochloridates or p-nitrophenyl phosphates, and metal alkoxides of nucleosides provides a new entry to nucleoside phosphates. This method has been applied to the dinucleotide synthesis.

Last year, we reported that human papilloma virus type 16 genome (HPV 16 genome) was detected in a case (S.Y.) of bladder carcinoma in situ (bladder CIS) (Cancer Res., 1988). Since then, a number of bladder tumors other than CIS were searched for HPV genome. However, no HPV genome was detected in the bladder tumors. From the results, we consider that HPV may not have a relation with all types of bladder tumor but with only a part of it. In the current report, the case (S.Y.) is presented more precisely than before, in particular on the characteristic bladder lesion. The patient was a 40-year-old female with immunodeficiency and anemia who was referred from a hospital with a complaint of asymptomatic pyuria. Cystoscopic examination revealed a bladder tumor, well-demarcated, white and velvety lesion with slight elevation. On November 25, 1987, she underwent total cystectomy, resection of the anterior vaginal wall and of a part of vulval skin, and ileal conduit formation. Postoperative course was stormy because of bleeding from the wounds and thrombophlebitis in the right femoral vein. In spite of the episodes, she eventually recovered and was discharged 2 months later. However she was readmitted 9 months later due to severe anemia which was ascribed to acute myelogenous leukemia. She is now on cancer chemotherapy for leukemia.

A double-blind placebo-controlled study of bunazosin for the treatment of symptomatic prostatism is reported, incorporating urologic departments of 25 hospitals. Four different doses of bunazosin hydrochloride was administrated orally to 174 patients having benign prostatic hyperplasia and 31 with bladder neck contracture for a period of four weeks; high dose group (45 patients, 3 mg/day for the first week followed by 4.5 mg/day for the next three weeks), middle dose group (45 patients, from 1.5 mg/day for the first week to 3.0 mg/day for the next three), low dose group (39 patient, 0.15 mg/day for the first to 1.5 mg/day for the next three) and a control group (40 patients, 0.125 mg/day for the entire four weeks). Subjective symptoms (urinary frequency, retarded urination, prolonged urination, condition of urinary stream and abdominal pressure at voiding) and objective signs (residual ratio, maximum and mean flow rate, voiding time) were observed and analyzed statistically. No bias in the background features was confirmed between any of the four groups. The subjective improvement rates evaluated by the attending doctors demonstrated a significant dose-dependent efficacy of bunazosin by H-test (p less than 0.01), although the objective improvement rates revealed no significant difference between any of the four groups. The global improvement rate evaluated by the same means demonstrated that the middle dose group was significantly superior to the control group (p less than 0.05 by U-test). According to each subjective symptom evaluated by the criteria of the drug efficacy, a dose-dependent significant (p less than 0.01) was noticed between the four groups in the improvement of the voiding condition. Although there was no significant difference by use of the H-test, the middle dose group had a significant superiority to the control group in the improvement rate of retarded voiding by use of the U-test (p less than 0.05). Only in the symptomatic cases of prolonged voiding, were dose-dependent significant differences observed between all four groups by use of the H-test (p less than 0.05). On the other hand, there was no significant difference between the four groups in the subjective or global improvement rates. Judging from the real data and the graded classification of objective signs, the high and middle dose groups were significantly superior to the control in terms of voiding time, and the high and low dose groups were the same as the control for residual urine ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrasonically guided puncture of the prostate was carried out in 10 patients with prostatic disease. Biopsy of the aiming portion of the prostate was performed with more certainty and safety by this method than the conventional blind procedure. In the 15 cases having the suspicion of seminal vesicle disorder, the seminal vesicle was punctured under ultrasound control. By this procedure, the seminal vesicle fluid was safely and accurately obtained.

Extended surgery was divided into 4 types per below. (1) Extended local resection (1 case). Resection of descending colon and splenectomy were performed in a case with invading left renal cancer. The patient died of cancer in 9 months. Three other cases with locally invading renal cancer were inoperable because of multiple metastases or poor general condition. (2) Thrombectomy in vena cava inferior (6 cases). Successful thrombectomy was carried out in 5 of our 6 cases. All the cases died of metastases of cancer within 4 years. In the literature, long survival is reported after complete resection of thrombus. (3) Resection of distant metastases (11 cases). Palliative surgery was performed in 5 cases with symptomatic brain metastases. After radical resection of solitary metastases, 2 died of cancer, 2 are alive with cancer and the remaining 2 are alive with no evidence of disease (NED). (4) Surgery for contralateral kidney (4 cases). Partial nephrectomy or enucleation of tumor was undertaken in 3 cases (2 NED, 1 death). In the 4th case, as the tumor appeared to invade deeply in the renal parenchyma, ex vivo partial nephrectomy followed by autotransplantation was done (NED). The results indicate that the minimum requirement for radicality should be complete extirpation of the tumor mass and that the indication for radical extended surgery includes presumably resectable intracaval thrombus, solitary metastases and contralateral renal tumor.

Bredinin, a new nucleoside antibiotic isolated from Eupenicillium brefeldianum, and steroids were used as immunosuppressive agents in 31 renal transplant patients; 17 of them received grafts from living-related donors and 14 from cadavers. The one-year graft survival rates were 100% in renal recipients from living donors and 69.2% in cadaver kidney recipients. There was no serious complication from the use of these immunosuppressive agents.

A rare case of vaginal stone in a male pseudohermaphrodite who had undergone plastic surgery for external genitalia 16 years ago is presented. It is recommended to remove the entire wall of vagina musculina at the time of plastic repair for hypospadias in a male pseudohermaphrodite.

Spin-lattice (T1) and spin-spin (T2) magnetic relaxation times of 25 human renal cell carcinomas and their assorted normal tissues were measured with a Bruker NMR spectrometer operating at 20 MHz. The tissue samples were examined within four hours after surgery. The results (mean +/- SD) were as follows: renal cell carcinoma, T1 = 638 +/- 168 msec and T2 = 109 +/- 41 msec; normal renal tissue, T1 = 594 +/- 165 msec and T2 = 100 +/- 24 msec. These results indicate that there was no significant difference in T1 and T2 between normal renal tissue and carcinoma. Our results suggest that it is difficult to separate relaxation times of renal cancer from those of normal parenchyma and that the difference between T1 and T2 alone does not permit recognition of renal cell cancer. Paramagnetic contrast agents may be useful in MR imaging to differentiate renal cancer from normal parenchyma.

Pulmonary changes induced by bleomycin were investigated in mice by using light and electron microscopy and by phospholipid analysis of the alveolar washings. The damage began in the endothelium of capillaries and was accompanied by interstitial edema and an appearance of enlarged macrophages along with hypertrophy of type II epithelial cells. This condition was followed by degeneration of type I cells. The denuded epithelium appeared to be repaired by two different mechanisms. In areas away from the bronchioles, division of existing type II cells and subsequent transformation into type I cells appeared to be the pattern of epithelial repair. In areas near the bronchiole, downgrowth of bronchiolar undifferentiated cells and subsequent maturation of these cells to type II and type I cells appeared to be prominent. Biochemically, total phospholipids and disaturated lecithin in the alveolar wash increased along with the increase of the alveolar lining layer and the hypertrophy of type II cells. This was considered to be consistent with the view that the hyperactive type II cells secreted more surfactant in the early phase of the experiment.

Recently, various progresses have been made in the treatment of the genitourinary malignant tumors. Effectiveness of the intravesical instillation of anti-cancer agents and biological reaction modifiers has been proved in the treatment and prevention of the superficial bladder cancer. Among them, superiority of BCG is now attracting attention of all the urologists. For the invasive bladder cancer, the M-VAC therapy (the combination chemotherapy of methotrexate, vinblastine, actinomycin and cis-platinum) has been found to be extremely useful. The multidisciplinary approach for the down-staging of the advanced bladder cancer has been advocated around the world. As for the prostatic cancer, that of the high stage is the main concern of the Japanese urologists, since the mass screening of the prostatic cancer has not prevailed in Japan. The LHRH agonists or the blockers of the androgen receptor have been replacing the classic antiandrogenic treatment consisting of castration and estrogen administration to treat the advanced carcinoma. On the other hand, the nerve-sparing total prostatectomy has been recommended for the low stage cancer by Walsh and associates to preserve potency. The testicular cancer has been most effectively treated with the combined chemotherapy. The PVB and VAB therapy are well known in the world. Lately, VP-16 (etoposide) was found to be a useful salvage agent. The least advance has been made in the treatment of renal cell carcinoma, although interferon therapy or LAK cell adoptive immunotherapy appears attractive.

A 65-year-old male with incomplete double penis is reported. He has a duplicated glans on a single shaft. Both glans each have an urethra surrounded by a corpora spongiosum. The right urethra drained a normal bladder and the left urethra vanishes near the seminal colliculus.

Twenty milligrams of (2"R)-4'-O-tetrahydropyranyladriamycin (THP) was administered intravenously to 14 patients with renal cell carcinoma and 11 with urinary bladder tumor at the start of surgery. Heparinized peripheral blood samples were collected at regular intervals and separated into plasma and blood cell fractions by centrifugation for the estimation of the THP concentration. The THP concentrations in the surgical specimens were also studied. In the tissue of renal cell carcinoma, the nuclear fraction was obtained by fractionation in order to estimate the THP concentration. The THP concentrations of the plasma and blood cell fractions in both renal cell carcinoma and urinary bladder tumor gradually decreased with the lapse of time after administration. In renal cell carcinoma, grade 3 tumors revealed lower tissue and nuclear concentrations of THP than those of grade 1 and 2 tumors. Likewise, the tissue and nuclear concentrations of high-stage tumors were lower than those of low-stage tumors. On the other hand, in urinary bladder tumors, the THP concentrations in the tumors were found to be higher than those in normal urinary mucosa and muscle.

A survivor of the Hiroshima atomic bomb experienced triple cancer of the urogenital organs after a long history of heavy smoking. The cancers comprised a clear cell carcinoma of the right kidney, transitional cell carcinomas of the urinary bladder, left ureter and left renal pelvis, and adenocarcinoma of the prostate.

During the 5-year period from October, 1978 to September, 1983, primary hyperparathyroidism has been found at our clinic in 16 out of 395 cases of urinary stones (4.1%) and in 12.6% of the recurrent or multiple stone-forming patients. Plasma-ionized calcium level and rapid rapid calcium load test were most valuable in the diagnosis of primary hyperparathyroidism. It has been proved that neck surgery for primary hyperparathyroidism prevents recurrence of urinary tract stones.

We evaluated the efficacy of terodiline hydrochloride (TD-758) in 23 patients with psychosomatic bladder, chronic prostatitis and chronic cystitis. The drug was administered at a dose of 24 mg once a day for 4 weeks. In 78% of the patients the symptoms such as urinary frequency and sense of residual urine improved. Only mild side effects such as thirst were noted. We concluded that terodiline hydrochloride was effective in this trial.

Between April, 1984 and March, 1985 in 14 centers, 33 patients with prostatic cancer of our 14 centers were randomized to subcutaneously receive either 125, 250, or 500 micrograms/day of ICI 118,630, an LH-RH analogue, for 12 weeks, and the clinical efficacy, safety and endocrinal effects of the drug by dose were examined. An objective partial response was obtained in 44.4% of the 125 micrograms-treated group, in 50.0% of the 250 micrograms-treated group, and 42.9% of the 500 micrograms-treated group, showing no significant difference between the groups. General subjective response rates in these three groups were respectively 75.0%, 62.5%, and 85.7%, not differing from each other significantly. No significant difference was observed in endocrinal effect which was seen in 58.3%, 66.7%, and 100% of 125 micrograms, 250 micrograms, and 500 micrograms groups, respectively. Medical castration was attained in 4.1 +/- 2.0 weeks on average. Adverse reactions observed included fever up to 37 degrees C in 1 of the 13 (7.3%) patients treated with 125 micrograms, and hot feeling at the injection site and flare in 1 of the 8 (12.5%) patients treated with 500 micrograms, which were all mild. These patients responded to further ICI 118,630 therapy without requiring any treatment for the adverse reactions.

Localization of alkaline and acid phosphatase activity was investigated in healthy human adrenal cortex by light and electron microscopy. The activity of both was found in the inner part of the adrenal cortex--mainly in the reticular zone. The reaction products of alkaline phosphatase were observed along the plasma membrane and those of acid phosphatase were observed mainly in the lysosomes and secretory vacuoles. The heavier deposit of phosphatase reaction products in the reticular zone may be explained by the fact that the reticular zone is most active in the steroidogenesis of glucocorticoid and adrenal androgen.

From November 1985 through September 1986, 20 cases of upper urinary tract calculi (14 kidney, 7 ureter) were treated by the one-stage procedure percutaneous nephrolithotripsy. Renal and ureteral calculi were successfully removed in all 20 cases (100%). After the procedure, a few small stone fragments remained in 3 cases (the rate of remnant stone : 14%). High fever was noted in 7 patients but did not last longer than 3 days. No patients required blood transfusion. The one-stage percutaneous procedure was considered a more efficient procedure to remove the upper urinary tract calculi, than open surgery or two stage percutaneous nephrolithotripsy. In one-stage percutaneous nephrolithotripsy, however, serum sodium concentration was lowered significantly after the procedure, although the hematocrit remained unchanged throughout. This should be carefully corrected by the supplement of irrigation fluid and intravenous infusion during the procedure.

In order to study the effect of Bestatin on superficial bladder cancer, the drug was used in combination with hyperthermia and Peplomycin therapy. The study was made using the following 2 groups. Group 1; Hyperthermic treatment with Peplomycin was used in 6 cases of bladder cancer. Group 2; Bestatin was given in combination with hyperthermia and Peplomycin in 15 cases of bladder cancer. As a result, complete or partial regression was obtained in 1 and 5 cases in Groups 1 and 2 respectively. Therefore, the combined use of Peplomycin and Bestatin in hyperthermic treatment for superficial bladder cancer appeared to be effective. Degeneration of tumor cells, irregularity of tumor structure, interstitial edema, fibrosis and cell infiltration were observed in the surgical specimens taken from effective cases, although the mechanism of action of Bestatin on tumors was clearly demonstrated upon histological examination.