The management of urinary calculous disease has been a treasured place also in urological history of Japan. Recently, innovatory procedures for stone removal have been introduced and the excellent advances of Endourology and ESWL (extracorporeal shock wave lithotripsy) revolutionized the surgical treatment of renal calculous disease.
However, some thoughtful members of urologists have been afraid that the majority of the urological surgeons might believe if they have already completed the treatment of urolithiasis and succeeded the resolution on the patients with renal calculous disease.
Now, I will write a saga of the investigations of this interesting and still important subject in the urological field of Japan, looking back my own way who have been interested in urolithiasis treatment and also its prophylaxis.
The goal of the treatment for urinary calculous patients should be the prevention of recurrent stone formation because the surgical treatment is only the removal of existing stones, even recent advance of innovatory procedures could confer the less invasive benefits on urinary calculous patients.
Some selective medical treatment programs have been introduced and emerged therapeutic importance to the prevention of renal stone formation and more will have elaborated in the future. Several investigations on the difficult mechanisms of stone formation have been also vigorously accomplishing by some urologists in Japan.
I hope that I would anticipate what is to come on the entire solution of the precise mechanism of stone formation and ultimate control of urolithiasis by successional young urologic investigators in near future.

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Combination chemotherapy with methotrexate, vinblastine, adriamycin and cisplatin (M-VAC regimen) was administered to 12 patients with advanced epithelial cancer of the urinary tract in a clinical trial undertaken to assess clinical efficacy of this multiagent therapy. This series comprised 11 males and 1 female ranging in age from 46 to 76 years (mean age: 63), with performance status (PS) being rated 0 in 2, 1 in 5, 2 in 2, 3 in 2 and 4 in 1 of these 12 patients. The site of primary lesion was bladder in 8, renal pelvis in 3 and ureter in 1. Histologically, these tumors were all identified as transitional cell carcinoma (grade 3) with the exception of 1 mixed type (transitional cell carcinoma plus squamous carcinoma). Nine of the patients had already their primary tumor resected surgically while the remaining 3 had undergone only biopsy. The site of metastasis was lung in 7, bone in 4 and lymph nodes in 3. In consideration of the patients' general condition, the dosages of the chemotherapeutic agents were set at 80% of those recommended by Sternberg. Of the 9 patients with primary tumor resected, 1 died of chemotherapy; of the remaining 9 patients, the M-VAC regimen brought about CR in 1 and PR in 4, hence with a response rate of 62.5%. The 4 patients showing PR underwent surgical resection of residual tumor and 2 of them achieved CR and have been free of a recurrence during a 33- or 29-month period of the chemotherapeutic regimen.
Of the 3 patients who had undergone biopsy only and whose primary tumor remained unresected, 1 had a PR with the multiagent regimen, hence the response rate for this small subgroup was 33%. Aside from the bladder and recutus abdominis muscle which were involved in a very limited number of cases, lungs and lynph nodes were most responsive to the chemotherapeutic regimen of all organs involved, with respective response rates of 57% and 33%. Use of the M-VAC regimen was attended by leukocytopenia in 11 patients (91%) and by nausea, vomiting, anorexia and falling off of hairs in all patients. Impairment of renal function was mild, however. In conclusion, the M-VAC regimen proved to be effective against advanced epithelial carcinoma of the urinary tract, especially in cases of postoperative recurrence, but ample care must be taken to avoid or minimize unwanted side effects of this combination chemotherapy.

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Ureteral peristalsis begins at the border between the major calyces and their minor calyces in the multicalyceal kidneys like those in the pig and human. The urologists often perform partial nephrectomy. But there has been no report on the impairment of calyceal and pelvic peristalsic function after partial nephrectomy. Therefore the objective of this study was to explore experimentally the effect of partial nephrectomy on the calyceal and pelvic peristalsis by electroomyographic tracing from the renal calyces, pelvis and ureter in isolated pig kidneys after successive resection of major calyces. Calyceal and pelvic peristalsis remained normal under the control of calyceal pacemaker as long as at least one of the upper, middle and lower major calyces of isolated pig kindey is intact. The observed facts suggest importance of the calyceal system as a pacemaker for maintaining normal ureteral peristalsis.

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Renal autotransplantation with/without extra-corporeal surgery was performed in 53 patients between September, 1975 and december, 1987. Original disease was obstructive disease of the upper urinary tract in 25 patients, renovascular hypertension and renal vascular disease in 13, renal calculous disease in 12 and renal cell carcinoma in 3. Ten of the 53 patients had solitary kidneys.
Three patients died on 14, 21 and 49 postoperative days of massive bleeding with disseminated intravascular coaglopathy caused by the rupture of transplant arterial anastomosis (1 patient with urinary obstructive disease) and sepsis caused by wound infection (2 patients with renal calculous disease). Two kidneys were removed on operative day and 8 postoperative days due to arterial thrombosis in 2 patients with aneurysma of intrarenal artery. The deterioration of renal function was observed in previously damaged kidneys of two patients with extensively damaged ureter. No other severe complications were observed.
In 23 of 24 patients with the obstructive disease of the upper urinary tract, disappearance or improvement of the obstructive change was observed after surgery. All 5 patients with renovascular hypertension showed normo-tension without administration of antihypertensive drugs after surgery. In 3 of 5 patients with an aneurysma of the intrarenal artery, the aneurysma was removed and rconstraction of the artery was performed successfully. Two patients with arterio-venous fistula and one patient with nut creacker syndrome had no severe hematuria with bladder tamponade after surgery. Ten of 12 patients with renal calculous disease were treated successfully without residual calculs by this procedure. Three patients who had solitary kidney with renal cell carcinoma were treated successfully by this procedure. These patients have no local recurrence 8 to 30 months after surgery. These results indicated that, this procedure is applicable to relieve the kidney with extensively damaged urinary drainage system, renal and/or intrarenal vascular disease and renal cell carcinoma. Most patients with calculous disease and renovascular hypertension should be primarily treated with extracorporeal shock wave lithotripsy and endoscopic surgery, and with transluminal angioplasty.

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We performed percutaneous nephrolithotomy (PNL) on 49 patients between May, 1986 and March, 1987. To investigate acute renal damage from PNL, we measured urinary NAG (N-acetyl-β-D-glucosaminidase) and γ-GTP (γ-glutamyl transpeptidase) activities before PNL and for 6 days after PNL in 24 patients. The NAG activities elevated beyond normal level in 23 patients and γ-GTP activities in 15 patients. NAG activities showed a peak level in the third day after PNL and γ-GTP activities in the next day of PNL. After the peak both enzymal activities got down gradually. There was no difference in NAG and γ-GTP activities between nephrostomy and lithotripsy in 2 staged patients. And the intrapelvic pressure during operation was at the normal level in 5 patients. Therefore, we think that the cause of NAG and γ-GTP activity elevation is a mechanical damage, not an influence of the irrigation fluid. Large stones, long operation time and 2 stage proceudre were the factors that produced high enzymal activities, because, we guess, the frequency of mechanical damages to the kidney increase in such cases. Postoperative pyrexia caused a slight increase in enzymal activities but preoperative hydronephrosis exerted no influence on both enzymal activities. We also measured creatinine clearance before and after PNL but no significant change was obtained. PNL causes only slight mechanical damage to the operated kidney which is reversible when assessed by NAG and γ-GTP activities and the glomerular function is not affected. Therefore, we conclude that PNL is a safe treatment for upper urinary tract stones.

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Antigens recognized by anti-γ-seminoprotein (γ-Sm) antibody and anti-prostate-specific antigen (PA) antibody were analyzed immunologically by Ouchterlony method and Western blotting method. The double immunodiffusion test demonstrated that anti-γ-Sm antibody and anti-PA antibody reacted against an identical antigen in seminal fluid or prostate homogenate. In the immunoblotting examination, anti-γ-Sm antibody and anti-PA antibody formed a single and identical band, which gave a molecular weight of 33, 000, in seminal fluid and prostate homogenate. This study demonstrated that anti-γ-Sm antibody and anti-PA antibody recognized a single and identical antigen in seminal fluid and prostate homogenate and suggested that an identical material could be measured in sera of patients with prostate cancer by immunoassay systems using anti-γ-Sm antibody and anti-PA antibody.

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The purpose of this study is to ascertain whether the urinary (turbulent) flow really causes the sounds during micturiton in humans. For this purpose the artificial bladder and urethra, which were made of silicon rubber (3M Co. Minnesota, U. S. A.), were used. The manometric device was attached to the bladder to measure the intravesical pressure. Outside the bladder neck a prostate like protrusion surrounding the urethra was made. A microphone was attached to this protrusion to detect the sound. A recording system was also adopted. The bladder was filled with 200ml of sterile eater. By pressurising the artificial bladder at 100cmH₂O, the water passed through the urethra. During this artificial voiding the sound detection was undertaken. At the same time uroflowmetry was also performed. It was demonstrated that sound spikes were recorded whenever water in the artificial bladder passed through the artificial urethra.

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Recently we have developed an entirely new method of sonic detection of lower urinary tract disorders during micturition. The detection of these sounds was performed by a data catching and recording system, consisting of a detector, amplifier, and recorder. This procedure was designated as “urophonography” and its recording as “urophonogram”.
Twenty-five patients with BPH before and three months after suprapubic prostatectomy and 10 healthy male volunteers underwent urophonography. The urophonograms were classified into four types. Type 1 was characterized by its diamond shape, while Type 2 was characterized by its random sound spikes. Type 3 was a mixture of Types 1 and 2. Type 4 had only few sound spikes. Analysis of these urophonograms also revealed that the frequencies of these urethral sounds belonged to the range from 0.4 to 1.5KHz. The amplitude (power) of the sounds was in the range of 40-60dB. Healthy volunteers belonged to Type 4. BPH patients belonged to Types 1, 2 and 3 at equal frequency. Comparison of uroflowmetric parameters with urophonograms revealed that Type 3 patients with BPH showed a lesser degree of micturition disturbances, which was consistent with the weight of prostatic tumors surgically resected. Urophonography was undertaken before and after the treatment on these patients. It was clearly shown that the pattern of urophonograms shifted to normal (Type 4). It was considered that urophonograms were useful for urodynamic investigation.

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Recently we have developed an entirely new method of sonic detection of lower urinary tract disorders during micturition. This procedure was designated as “urophonography” and its recording as “urophonogram”.
Sixteen patients with prostatic cancer before and three months after anti-androgenic therapy and ten healthy male volunteers underwent urophonography. The urophonograms were classified into four types. Type 1 was characterized by its diamond shape, while Type 2 was characterized by its random sound spikes. Type 3 was a mixture of Types 1 and 2. Type 4 had few sound spikes. Analysis of these urophonograms also revealed that the frequencies of these urethral sounds belonged to the range from 0.4 to 1.5KHz. The amplitude (power) of the sounds was in the range of 40-60dB. Healthy volunteers belonged to Type 4. Prostatic cancer patients belonged to Types 1, 2 and 3 at 18.8, 68.8, nad 12.4%, respectively. After the treatment the percentages of Types 1, 2, 3, and 4 changed to 18.8, 50.0, 0, and 31.2%, respectively. Comparison of uroflowmetric parameters with urophonograms showed that Type 2 patients showed a lesser degree of micturition disturbances, evidenced by these parameters. It was considered that urophonograms were useful as urodynamic investigation.

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In vitro and in vivo cytotoxicity tests were carried out using the YTS-1 human bladder carcinoma cell line.
The lethal effects of a 1-hour treatment with 5 anti-cancer agents (Cisplatin [CDDP], Cytosine arabinoside [ara-C], Adriamycin [ADM], Etoposide [VP-16] and Carboplatin [CBDCA]) on the YTS-1 cells grown as monolyer were examined quantitatively by the regrowth assay methods. In addition, the lethal effects of 3 anti-cancer agents (CDDP, ADM, ara-C) were also examined in vivo. Moreover the effects of simultaneous combinations of CDDP and ara-C, and ADM and ara-C were assessed in vitro and in vivo.
In vitro studies showed that, of these single agents, ADM and ara-C were cytotoxic judging from the human maximal plasma concentraiton of drugs, whereas CDDP, VP-16 and CBDCA were not. Combinations of CDDP and ara-C, and ADM and ara-C showed more than additive effect.
In vivo studies on YTS-1 tumors implanted to athymic nude mice (BALB/c) showed that ADM was the cytotoxic agent. Although CDDP alone or ara-C alone was not cytotoxic to YTS-1 tumors, combination of CDDP and ara-C showed antitumor activity. These results show that combination of CDDP and ara-C is synergistic. The most effective combination was observd to be ADM and ara-C, but severe loss of body weight was also observed.

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To determine the availability of ultrasonography in follow-up of postoperative pelviureteric dilatation, 35 children, who had previously been operated on in some part of the urinary tract, were examined by both excretory urography and ultrasonography.
Of 59 kidneys shown to be with a dilated collecting system on excretory urography, 58 were correctly detected by ultrasonography, with a sensitivity of 98.3%. The grade of dilatation of the collecting system diagnosed by ultrasonography was corresponded to that by excretory urography in 99 of 123 kidneys (80.5%).
At the level of the lower calyx, 40 of 43 ureters which measured 5mm or greater in diameter on excretory urogram, were detected by ultrasonography. Thirty of 36 ureters posterior to the bladder with a diameter of over 5mm were also detected by ultrasonography. The diameters of the ureters measured by ultrasonography were well correlated with those on ecretory urogram.
These results suggest that the availability of ultrasonography is so high that it could substitute for excretory urography in follow-up of postoperative hydronephroureter in children.

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Tumor tissue and nontumerous tissue of 31 patients with testicular tumor were examined by the peroxidase antiperoxidase (PAP) procedure using the primary antibody against glutathione S-transferase (GST). Histology of primary tumor was classified as seminoma in 10 cases, non-seminoma in 18 (including 2 cases of yolk sac tumor), and malignant lymphoma in 3.
Tumorous tissues except one with yolk sac tumor failed to be stained with GST. The seminiferous tubules of the nontumorous testicular tissue had a positive reaction in the infant cases, but not in the adult cases. The degenerated seminiferous tubules involved in the testiular tumors also had a positive reaction in all the cases. Leyding cells had a positive reaction in all the cases. In particular, diffuse Leydig cell's hyperplasia was observed in a case with high serum beta hCG and urinary hCG levels.
These data may be relevant in explaining the inherent hypofertility of these patients.

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From 1979 through 1988, 64 men and 16 women (age range 36-82; mean 63 years) with bladder cancer underwent pelvic lymph node dissection and radical cystectomy with urinary diversion. Bilateral common iliac, external iliac, internal iliac, obturator and presacral nodes were removed and examined. The frequency of involvement of each nodal group was the highest at the common iliac and the external iliac nodes followed by the obturator, presacral and internal iliac nodes. The incidence of lymph node metastasis increased with the tumor grade and pathological stage. The incidence of positive nodes is 3.7% in patients with P1 tumors, 10% in P2, and 17% in P3 tumors. Of these patients, 9 were with nodal metastasis; seven died of metastatic cancer 3 to 37 months post-operatively, two were alive for 4 to 41 months without evidence of recurrence. The mean survival time was significantly longer than that of the historical control group (1975-1978 total cystectomy without node dissection).

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Beta-adrenoceptor subtypes in detrusor and trigonal muscle of rabbit, canine and human urinary bladder were studied by in vitro techniques recording contractile force and by measuring intracellular cAMP content. The results of contractile studies were correlated with the intracellular cAMP levels. In the rabbit bladder, only β₂-receptors were found in the detrusor though both β₁-and β₂-receptors were found in the trigonal muscle. In contrast, both β₁ and β₂-receptors were present in both detrusor and trigonal muscle of canine bladder. Human detrusor had only β₂-receptors. Thus there are species differences in beta-adrenoceptor subtypes in urinary bladder smooth muscle.

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The effects of various α-adrenergic agonists and antagonists on the contractile properties of the isolated urethra of male and female rabbits were examined and the population of α₁- and α₂-adrenoceptors, using radioligand receptor binding techniques, was also quantified to define the functional role of postsynaptic α-adrenoceptors in urethral smooth muscle.
Norepinephrine, epinephrine (non-specific α-adrenergic agonists) and phenylephrine (α₁-adrenergic agonists) induced increases in contractile force in both the male and female urethra. Clonidine (α₂-adrenergic agonist) caused a relatively large contractile response in the female urethra but only a small contractile response in the male urethra. Receptor binding studies indicated that the male urethra contains almost equal amounts of α₁- and α₂-adrenoceptors (32vs. 34fmol/mg protein, respectively) whereas the female urethra contains a significantly greater density of α₂- than α₁-adrenoceptors (122vs. 34fmol/mg protein, respectively). Our studies have indicated that: (1) both α₁-and α₂-adrenoceptors cause contractile responses in male and female rabbit urethra; (2) the greater response to α₂-agonist in female than male urethra is correlated with a higher density of α₂-adrenoceptors in this tissue.

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Subjective symptoms on voiding were analysed in 419 subjects who were submitted to mass screening program for prostatic diseases by means of transrectal sonography, consisting of 296 normal subjects and 123 cases of benign prostatic hypertrophy (BPH).
Subjective symptoms were encountered in about 70% of normal subjects and 80% of BPH cases. However, almost all normal subjects complained of single symptom, while many BPH cases of multiple symptoms. The frequency of subjective symptoms in BPH cases was significantly higher than that in normal subjects.
Relationship between each subjective symptom and the presumed circle area ratio (PCAR) was evaluated in all cases of BPH. As the results, it was proved that the higher the PCAR was, the more the appearance of the urinary prolongation and nocturnal frequency were encountered. Moreover, it was presumed that these symptoms on voiding, especially the urinary prolongation, correlated closely with the degree of urinary obstruction in BPH patients.

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This paper is the 12th report in a series of studies on the application of microexplosion to medicine and biology.
Microexplosion lithotripsy is a newly developed technique in our clinic to crush urinary stones with small quantities of explosives. A systematic research project has been performed since the first report of microexplosion lithotripsy in 1977. As a result, microexplosion was successfully applied to the destruction of bladder stones in 130cases from 1981 to 1988.
In blasting to crush rocks in industrial works, two kinds of blasting are available: external charge blasting and confined blasting. The detonation power of the latter is 10 to 50 times larger than that of the former.
A detruction test using several kinds of spherical form model calculus and lead azide explosive was performed. The formula to calculate the suitable explosive dose was determined experimentally as shown below.
L: Dose (mg)
L=CD² C: Coefficient of blasting
D: Stone diameter (cm)
Thus the theory in general industrial blasting with massive explosives was proved to be effective also in microexplosion with small explosives.
An original electric drill system was developed to make a hole in stones for confined blasting. 60cases, including 2cases of giant bladder stones over 100g in weight, were successfully treated by confined blasting using this system without any complication.
We consider that any bladder stones, however big or however many, can be treated by microexplosion lithotripsy with confined blasting.

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