Immunotherapy gained popularity as a treatment modality for malignant diseases in the 1960s. A number of trials, using tumor vaccines, immunopotentiators, interferons, cytokines and others, demonstrated antitumor effects in several urological malignancies, and, to date, immunotherapy plays a major role in treatment of advanced renal cell carcinoma and superficial bladder carcinoma. Interferon or interleukin-2, which became available for large scale clinical trial with the development of bioengineering, however, were shown to be not effective as initially expected, by single agent. Rational design of new strategies with mutiple agents in combination based on basic and clinical research, should provide progress in treatment of urological malignancies.

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The present study was conducted to examine the characteristics of pyelorenal backflow related with the changes in renal pelvic pressure. Forty rabbits weighing approximately 3.0kg were used in this experiment. The renal pelvis was continuously perfused with PSP solution through the double lumen catheter placed above the ureteropelvic junction. The renal pelvic pressure was also recorded during the intrapelvic perfusion. Simultaneously, PSP concentrations in blood and urine excreted from the contralateral kidney were measured.
During the intrapelvic perfusion with PSP solution, PSP blood concentration began to increase immediately and reached maximum within 1 or 2 minutes after a start of perfusion. Then, its concentration gradually decreased toward the constant, low levels. The urinary concentration of PSP showed the same change as the blood concentration with a time lag of 1 or 2 minutes. A compartment analysis showed that this backflow curve composed of an early phase and a late phase. The early phase was characterized by a rapid increase and following decrease (exponentially declining) in PSP concentration. The late phase was a portion of constant PSP concentration in the backflow curve.
A maximum PSP concentration in the early phase was elevated with an increase in the increment rate of renal pelvic pressure. There was a significant, positive correlation between the maximum PSP urinary concentration and the increment rate of renal pelvic pressure (dp/dt). The constant values of PSP concentration in the late phase could be correlated with neither increment rate nor absolute values of renal pelvic pressure.
It seems from these results that in the early phase, a passive transport plays an important role in dynamics of pyelorenal backflow because and extent of reflux depends on the changes in renal pelvic pressure. The late phase of backflow may result from an active transport system in the perfused kidney. However, further studies are necessary to clarify this late component of backflow.

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With the development of extracorporeal shock wave lithotripsy treatment, the duration of hospitalization for stone patients fortunately has become shorter. However, a detailed analysis of lithogenesis is not possible during such patients' short hospital stays. We prepared a standard diet to be eaten at home for investigation of lithogenesis at the out-patient clinic. This diet was nutritionally well-balanced and contained the following: energy: 2000 Kcal, total protein: 70-75g, animal protein: 30-35g, carbohydrate: 510g, fat and oil: 50-60g, calcium: 600-630mg and magnesium: 320mg. The urine of 24 male patients with stones on a free diet and the same patients after 3 days on the standard diet was analyzed for urea-nitrogen, uric acid, sodium, calcium, phosphorus, magnesium, citric acid and oxalic acid. The results were compared with those in 17 healthy male subjects who were eating the standard diet (controls).
It was found that 66% of hypercalciuria (>=300mg/day) on a free diet became normocalciuria on the standard diet. The hypercalciuria was therefore thought to be of dietary origin. Moreover, urinary excretion of urea nitrogen, uric acid, sodium and phosphorus by patients remarkably decreased after 3 days on the standard diet, which was not different from that of controls.
These results suggest that the standard diet at home is useful in the screening of hypercalciuria and also quite adequate for patients with stones.

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We reviewed our experience of the application of a new urethral stent (PROSTAKATH^®) for 8 patients with prostatic outflow obstruction from December 1989 to March 1990. 6 patients had required the Foley catheter for several months because of chronic urinary retention. 2 were dysuric patients having a higher bladder residual urine volume. All were in a high risk group for surgery. 7 out of the 8 patients were treated successfully. The stent was not placed in one. All 7 patients in whom the urethral stent was placed voided freely after placement of the stent. Bladder residual urine was not detected by the ultrasound sonography except in one patient.
The urethral stent used in this study was a spring-like spiral with an outside diameter of 21Fr, it is made of gold-plated stainless steel. Under local anesthesia, it can be easily inserted using a 6-7Fr. ureteral catheter as a guide wire under ultrasonic scanning guidance.
During the follow-up period of 5-8 months, 1 patient had an episode of migration of the stent to the bladder 2 months later, which was removed endoscopically, and a new stent was placed. Side effects were observed in 2 patients; one complained of strong discomfort and the other suffered from urge incontinence. Both symptoms were ameliorated during the follow-up period.
We conclude that the urethral stent is an effective device as a non-invasive treatment of prostatic outflow obstruction.

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Fourteen patients with metastatic renal cell carcinoma (RCC) were treated by systemic administration of autologous lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2). Pulmonary metastases alone were found in 9 cases, pulmonary and mediastinal nodal metastases in 3, and pulmonary and bone metastases in 2. LAK cells, generated by incubation in 2 units/ml of IL 2 for 3-4 days, were intravenously administered once or twice a week. In addition, beginning on the day of the first LAK cell infusion, 1000 units of IL 2 diluted in normal saline were intravenously infused once or twice a day with occasional supplementation of 1000 units of IL-2 on each day of LAK cell infusion. The total number of LAK cells and total amount of IL-2 administered per patient in this study ranged from 0.8×10¹⁰ to 6.9×10¹⁰ cells and from 3.3×10⁴ to 21.4×10⁴ units, respectively. As toxic effects caused by the infusion of LAK cells, headache, shaking chills, fever and leukocytosis were found in all 14 cases. Side effects possibly induced by IL-2 infusion were tolerable fever, fluid retention (body weight gain of 2-3kg) and eosinophilia. No objective regression of mediastinal nodal or bone metastases was observed. In regard to lung metastases, however, partial and minor responses were observed in 3 and 2 cases, respectively. One of the 3 patients with a partial response was clinically free of disease after undergoing a thoracotomy for resection of residual lesions, but a brain metastasis was detected 10 months after the thoracotomy. The remaining 2 patients are being closely followed up at present. In 3 of 11 patients who showed a minor response, no change or progressive disease, brain metastases were observed during or after the immunotherapy. Furthermore, we examined the possibility of selection of suitable candidates for this therapy on the basis of the degree of in vitro LAK activity against autologous cultured tumor cells in 6 patients, but there was no significant correlation between in vitro autologous tumor cell lysis by LAK cells and the clinical response to immunotherapy.
In conclusion, although a complete response could not be obtained, it can be said that this immunotherapy may be effective against RCC, in particular lung metastases, since a partial response was achieved in 3 of 14 patients. However, it should be taken into consideration that this immunotherapeutic approach may have a risk of increasing the frequency of brain metastases.

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Urinary heparan sulfate (U-HS) and chondroitin sulfate (U-ChS) were isolated and partially purified using two steps of anion-exchange chromatography (DE-52 and Dowex 1×2). Uronic acid content of these urinary glycosaminoglycans (GAGs) and commercial heparan sulfate (C-HS) and chondroitin-6-sulfate (C-C6S) was as follows; U-HS: 22.4%, U-ChS: 32.0%, C-HS: 41.6%, C-C6S: 36.0%.
The inhibitory activity of these GAGs on calcium oxalate crystal growth was examined using the crystal-seed system described by Koide et al. The influence of uric acid on the inhibitory activity of the GAGs was also studied. U-HS and U-ChS exhibited nearly equal inhibitory activity to their respective commercial preparations. The inhibitory activity of U-HS was stronger than that of U-ChS. Uric acid suppressed the inhibitory activity of both, and the degree of suppression was stronger in U-ChS than in U-HS.
The molecular weight of the urinary GAGs was compared to that of the commercial chondroitin-6-sulfate (C6S; m. w. between 40, 000 and 80, 000) by gel-filtration using Sephacryl S-300HR. C6S was eluted slightly behind the void volume. U-ChS was eluted much behind C6S. Therefore, the molecular weight of U-ChS was thought to be much smaller than that of C6S. U-HS was eluted into two peaks; the first one at the void volume and the second one between the peaks of C6S and U-ChS. These findings indicate the possibility that part of U-HS exists in the form of proteoglycan.

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We performed kidney preserving surgery for renal cell carcinoma in 10 patients with a solitary kidney or bilateral tumors. Two had cancer in a solitary kidney (contralateral kidney was nephrectomized for benign disease) and 8 had bilateral renal tumors, 3 and 5 of the latter 8 patients being asynchronous and synchronous, respectively.
The kidney preserving surgery included partial nephrectomy in 3 patients and enucleation in 7 patients and was performed in situ and ex vivo followed by renal autotransplantation in 4 and 6 patients, respectively.
Of the 10 patients, 4 are still alive after 2 years and 11 months-5 years and 6 months. Death occurred in 6 patients. Excluding one non-resectable patient and 2 patients of non-cancer death, 3 patients survived for 3 years-8 years and 8 months. The 10 patients, excluding one non-resectable, showed actuarial survival rates of 89, 89 and 63.3% for 1, 3 and 5 years, respectively, and excluding patients of non-cancer death, the above rates were 100, 100 and 85.7%, respectively.
Postoperative local recurrence was found in 1 of 3 patients of partial resection and 2 of 7 patients of enucleation, and the latter 2 patients were those who had synchronous bilateral tumors and underwent renal autotransplantation following enucleation of a number of tumor nodules from seemingly less involved kidneys and contralateral radical nephrectomy; recurrence in the grafted kidney was already observable in the early postoperative period, which indicated re-growth of the residual tumor rather than recurrence.
Based on our experiences kidney preserving surgery, in particular enucleation, was proved to be an excellent surgical approach in that it could provide patients with better survival with high QOL, in spite of the limited radicality in the case of multiple tumors.

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We conducted mass screenings for prostate diseases on male subjects over fifty years of age in three separate areas in Hokkaido. Prostate carcinoma and benign prostatic hypertrophy were searched in the 1, 764 participants.
Histopathologically proven prostate carcinoma was found in twenty-two (1.25%) of the 1, 764 participants. This frequency of carcinoma was higher than any other carcinoma found in the mass screenings for gastric, uterine, breast and lung carcinoma in Hokkaido. Of the 22 prostate carcinomas found, 68% were in the early stage (stage B). This stage distribution was clearly distinct from that of prostate carcinoma found on the hospital visit, most of which had already progressed to an advanced stage. These results indicate that mass screening for prostate carcinoma on ≥50 year old-male subjects is efficient in finding carcinoma of all stages but, in particular, carcinoma of early stage, when compared with mass screening for other carcinomas.
BPH, defined as a moderately or markedly enlarged prostate on rectal palpation, was found in 10% of the participants. Questionnaire on subjective symptoms of voiding disturbance in the participants has confirmed that these symptoms, mainly elicited by BPH, become manifested in fifties and more frequent with age.
Of thirteen patients with prostate carcinoma who received both rectal examination and prostate-related markers measurement in serum at the time of mass screening, three without induration of the prostate were diagnosed as having carcinoma from an abnormal value of the serum markers. This result suggests that the marker(s) is one of the useful screening tests for detecting carcinoma. However, the most appropriate system for marker determination (single or combination assay) and its cost-benefit issue remain to be determined.

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We reviewed 12 patients who underwent myocutaneous flap plasties to reconstruct the genital skin. The patients included 9 who underwent a radical excision of malignant tumor involving the genital, inguinal or sacral skin, 1 with an extensive radiation ulcer of the genitalia and 2 with an ulcerating cancer of the scrotum or groin. In the latter 2 patients the plasty was intended to cover an unresectable ulcerating cancer. A gracilis myocutaneous flap was used in 10 patients, and a tensor fascia lata myocutaneous flap in 2 patients. Postoperatively, partial or total necrosis of the skin of the flap developed in 8 patients. In 4 of these, infection complicated the necrosis. Although debridement, resuture or free skin trnasplantation was needed in these patients, wound healing was ultimately achieved in 10 patients who underwent radical excision of malignant tumor or radiation ulcer. In contrast, the intended coverage of an unresectable ulcerating cancer was unsuccessful in two other patients. No patients had motor disturbance after wound healing. However, one patient developed stricture of the urethra and vagina which had been opened through the flap, and another patient complained of gait disturbance and difficult defecation because of an swelling of the flap around the anus. Incision or excision was required to relieve the complaints in these 2 patients. These results indicate that a myocutaneous flap is useful to cover an extensive skin defect of the genitalia, but may be accompanied by postoperative complications particularly before wound healing. Appropriate management is necessary to achieve the intended reconstruction.

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From October, 1987 to September, 1989, 53 staghorn calculi of 51 patients underwent extracorporeal shock wave lithotripsy (ESWL) monotherapy by using Dornier HM3 lithotriptor. All patients were treated with double J stenting preoperatively. Mean number of shock waves was 6092 and mean number of sessions was 2.1. In 52 out of 53 kidneys (98%), the stones were disintegrated completely. Complete removal of the stone were observed in 29 kidneys (55%) 3 months after the last ESWL treatment. Complications consisted of fever attack (more than 38°C) (26 patients), ileus (2), subcapsular hematoma (2) and gastrointestinal hemorrhage (1). They could be conservatively treated except one case with percutaneous nephrostomy. Supplementary procedures for the stone street were necessary in 23 patients. They consisted of ESWL (16 patients) and transuretheral lithotripsy (7). The indication of this procedure for the treatment of staghorn calculi was also disccussed.

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To clarify the mechanism of metabolic changes after using intestinal segments as a urinary tract, absorption of urinary constituents from the ileum was studied in dogs.
An isolated distal ileum (30cm in length) was anastomosed to the urinary bladder in each dog. Although these animals maintained the normal renal function throughout the experimental period, mild acidosis was noticed one month after anastomosis and it became severe after six months.
Stagnation of a urine-like solution (artificial urine: AU) in the isolated ileum resulted in an absorption of 66% of the instilled solvent on average during 60 minutes. The average absorption rates of each AU constituent were as follows: sodium 63%, potassium 80%, chloride 83%, phosphorus 68%, magnesium 34%, urea nitrogen 93% creatinine 56%, and ammonia 97%. On the contrary, calcium increased in the stagnated fluid by 21%.
In spite of the severe histologic changes in the villi of the ileal mucosa, which became atrophic and flat, no deterioration in the absorptive capacity of the AU constituents was noticed during the six month experimental period.
Furosemide administration suppressed the absorption of urinary constituents, especially water and sodium. On the other hand, the absorption of urea nitrogen and ammonia was scarcely affected.
Perfusion of the isolated ileum with AU (0.5ml/min) for 60 minutes resulted in an absorption of 59% of the solvent and 50 to 86% of each constituent. The rate of absorption was reduced after increment of the perfusion rate.
In conclusion, the absorption of urinary constituents occurs rapidly and significantly. The absorptive capacity remains longer regardless the severity of histological changes of the ileal mucosa. These results indicate that an increase in frequency of micturition, an increase in urine volume, and reducing the time of urinary stagnation in the ileum are important to prevent metabolic acidosis after utilizing the ileum as a urinary tract.

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Seventy-seven patients with primary malignant testicular tumors were treated in our hospital. Twenty-five of them were given antineoplastic agents containing cis diamine dichlorplatinum (CDDP). In three long-term survivors, new malignant testicular tumors developed metachronously and had different histological findings from those of the initial tumors.
Case 1. A 28-year-old patient with a yolk sac tumor of the left testicle, stage IIIO, developed metastasis to the supraclavicular lymph nodes five years after radiation. Chemotherapy containing of VP-16 (837mg), CDDP (1050mg), vincristine (32mg), bleomycin (480mg), and actinomycin-D (16mg) achieved complete remissin. Four years 11 months later a seminoma of the contralateral testicle, stage I, was disclosed and he died of cancer 11 years and four months after the onset of the initial disease.
Case 2. A 30-year-old patient with testicular teratoma, stage IIIA, on the right side gained complete remission after a CDDP containing chemotherapy. One year and four months after the beginning of the CDDP use (1, 300mg totally as CDDP) a seminoma on the contralateral side, stage I, was detected. He died of cancer eight years and two months after his initial tumor was detected.
Case 3. A 37-year-old patient with combined tumor of seminoma and yolk sac tumor of the right testicle, stage IIIO, was free from disease for six years and five months under chemptherapy. At this point a seminoma, stage I, of the contralateral testicle was newly found and treated by radiation. He has been free from disease and his clinical period lasted for nine years and 11 months since the discovory of the initial tumor.
These three patients received large amounts of anti-neoplastic agents, including CDDP in common, for a considerrable period. a large amount of antineoplastic agents in a long-term use may be tumorigenetic in the intact testicle. Careful attention to the intact testicle is to be paid to detect such uncommon lesions in an early stage.

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Though the local hyperethermia for the management of benign prostatic hyperplasia has drawn much attention as one non-surgical treatment, no definite conclusion could yet be obtained in terms of the efficacy. In this study local hyperthermia was induced in evaluable 33 cases with benign prostatic hyperplasia using Primus, and the effectiveness of this modality of treatment was investigated by analysing the subjective and objective response following hyperthermia.
The prostate was heated transrectally up to 43°C with 915MHz microwave for one hour. Hyperthermia was carried out twice a week for ten times for the sake of thermotolerance. Urinanry obstructive symptoms were divided into diurnal and nocturnal frequency, urinary urgency, the degree of urinary stream, hesitancy and dribbling. Each symptom was described before and after the treatment according to the scoring system. Moreover, objective changes of urinary flow and prostatic size were estimated by the residual urine volume, uroflometry, rectal palpation of the prostate and echography.
Hyperthermic treatment improved urinary flow markedly, but no appreciable alteration could be observed as to the size of the prostate. The overall efficacy, including subjective and objective response, could be summarized as 37% of effectiveness, and 33% of slight effectiveness, that is, 70% of effective ratio. As to the side effect, anal pain was noted in few cases of the present series. Therefore, transrectal hyperthermia may be a suitable modality for non-surgical treatment of benign prostatic hyperplasia.

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Ninety-four kidneys with renal stones≤20mm in diameter were treated by extracorporeal shock wave litotripsy (ESWL) using a Dornier modified HM3 lithotripter and the results were compaired with those of 98 kidneys with similar size stones treated with a Dornier HM3 lithotripter. The Dornier modified HM3 lithotripter is equipped with a new type of shock wave generator with a reduced capacity for 30% less pressure peakes at the same voltage. It has an enlarged ellipsoid leading to a smaller focus and a reduced pressure per area at the shock wave entry into the skin. All treatments of modified HM3 litotripter series were performed under only intravenous analgosedation, without epidural anesthesia. The number of shock waves in the modified HM3 series ranged 900 to 6000, with the mean values of 2863±1234, which was 1.55 times as that in the Dornier HM3 series. Complete disintegration was achieved in 94 of 94 modified HM3 series kidneys and 98 of 98 kidneys of HM3 series. Complete removal of the stone was done at 72.6% in the modified HM3 series and at 70.4% in the HM3 series 3 months after ESWL. There were no severe complications in both modified HM3 series and HM3 series. Renal damage caused by ESWL was monitored by the level of urinary enzyme, N-acetyl-beta-glucosaminidase (NAG) and β2 microglobulin (β2MG) and the level of urinary protein. The levels of NAG, β2MG and urianry protein in the HM3 series were higher than those of the modified HM3 series. These results indicate that (1) a modified HM3 lithtriptor was useful for the treatment of urinary stones, and (2) renal damage seemed to be less with a modified HM3 lithotripter than with an HM3 litotripter.

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The clinical significance of serum basic fetoprotein (BFP) in prostatic cancer was investigated together with serum prostatic acid phosphatase (PAP), γ-seminoprotein (γ-Sm) and prostate specific antigen (PA).
Investigated in this study were 40 patients with prostatic cancer, ranging in age from 50 to 85 years (mean age: 69.5 years). According to clinical staging, 3 cases (7.5%) had a stage A disease, 10 cases (25.0%) a stage B disease, 7 cases (17.5%) a stage C disease, and 20 cases (50.0%) a stage D disease. The positive rates for serum BFP, PAP, γ-Sm, and PSA were 60.0, 45.0, 63.6, and 68.4%, respectively, and these rates increased as the stage advanced. The above results suggest that BFP is the most useful marker of the four for monitoring prostatic cancer.
In a combination assay of these four markers, 29 (87.9%) of 33 patients with prostatic cancer could be diagnosed by observing an elevated serum level in one of the markers. This suggests that a combination assay of BFP, PAP, γ-Sm and PSA in patients with prostatic cancer is useful for diagnosis and monitoring of the disease.

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We studied 20 cases of neurogenic bladder with vesico-ureteral reflux retrospectively. Seven patients voided with Valsalva's maneuver and 12 patients were managed with clean intermittent catheterization, but one patient required permanent urinary diversion because of uncontrollable urinary tract infection. The patients were followed by intravenous pyelography, radioisotope renogram, voiding cystourethrography, determination of serum creatinine level and urodynamic study. Anti-reflux surgery was performed in 22 ureters and reflux resolved in 19 ureters. Among 12 ureters not treated by anti-reflux surgery, reflux disappeared in 5 ureters and improved in 2 ureters. Of 5 ureters, reflux resolved after clean intermittent catheterization in 2 ureters, and remained stable without recurrent infection or renal deterioration in the remaining 5 ureters. Regardless whether antireflux surgery was done or not, most of the patients who had high grade reflux and obstructive renal damage on radioisotope examinations had marked low compliance bladders. Our experience suggested the necessity of a suitable treatment to improve bladder compliance before considering anti-refux surgery.

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We reviewed enuretic children among patients with congenital lower urinary tract obstructions experienced in the Department of Urology, Hyogo College of Medicine during 16 years from 1974 to 1989. Among 612 patients with congenital lower urinary tract obstructions, 139 (22.7%) had enuresis nocturna and/or diurna. The incidence of enuresis was 24.7% with posterior urethral valve (77 cases), 50.0% with anterior urethral valve (6 cases), 23.8% with congenital bulbar urethral stenosis in boys (303 cases) and 19.9% with congenital distal urethral stenosis in girls (226 cases). Diurnal enuresis was more common in enuresis associated with congenital lower urinary tract obstructions than in usual enuresis. In urodynamic examinations, more than half of enuretic children with congenital lower urinary obstructions showed hyperactive detrusor activity. Treatment of congenital lower urinary tract obstructions through operation resulted in cure or amelioration of enuresis in about 80% of the patients. Enuresis associated with lower urinary tract obstruction or neurogenic bladder is sometimes called complicated enuresis and it is an important role of a urologist to differentiate complicated enuresis from simple enuresis.

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A 62-year-old male was admitted with abnormal shadow in chest X-P. CT and other examinations were done, and he was diagnosed left renal cell carcinoma with metastatic lung cancer. He rejected operation and was discharged. We gave him α-interferon injection every day. About 5 months later, he complained of fever and dyspnea, and was admitted. On the 10th day after admission, he died suddenly with massive hemoptysis. This hemoptysis was from the pulmonary artery, which was surrounded by tumors and ruptured into the trachea. Pathological diagnosis was double cancer, such a case is very rare with a primary lung cancer (oat cell carcinoma) which has metastasized into a renal cell carcinoma (common type, clear cell subtype).

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A patient with testicular cancer (non-seminoma, stage IIB) who had undergone resection for primary disease and retroperitoneal lymph node dissection as well as chemotherapy and radiotherapy 6 years before developed iatrogenic retrograde ejaculation. The infertility was treated by oral medications, including herbal medicine and injections of a hormone preparation as well as artifical insemination of husband (AIH). After 24 sessions of AIH for 4 years, his spouse gave birth to a healthy baby girl.
We believe that for patients with iatrogenic retrograde ejaculation AIH is an effective method of increasing fertility to be employed more often.

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