The several problems of refluxnephropathy and refluxglomerulopathy are reviewed and discussed. From my own experience of primary VUR in 901 children and of secondary VUR in 195 children I would like to lay stress on my cherished opinion that for the treatment of VUR all of clinical and subclinical infravesical obstruction should be at first ruled out.

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Plasminogen activators (PA) have been reported to be associated with fibrinolysis. The amounts of PA in urine, plasma, and tissues of patients with renal cell carcinoma were determined by measuring the amounts of two kinds of antigens, urokinase type (u-PA) antigen and tissue type (t-PA) antigen, by highly sensitive enzyme-immunoassay.
The u-PA antigen level in urine showed neither daily variation nor age-relationship. It was, however, significantly higher (164.2±93.5×10²U/gCr) in patients with renal cell carcinoma than in healthy subjects (56.8±22.4×10²U/gCr) (p<0.01). The amount of u-PA antigen in urine tended to be higher in patients with high grade or stage cancer than in those with cancer of low grade or stage, though not statistically significant. The u-PA antigen content in tissues appeared elevated in tumors (8.90±6.00×10^-1U/g wet tissue) in comparison to normal renal cortex and medulla. However, the difference was not significant, as the cancer samples consisted of various tissue components including necrotic or hemorrhagic tissue in addition to cancer cells.
Although the t-PA antigen content in urine was too unmeasurably small in 29% cases by the present method, there was no significant difference between patients with renal cell carcinoma and healthy subjects. The plasma level of t-PA antigen tended to be elevated in renal cell carcinoma group (7.87±5.60U/ml) compared to the control group (5.7±2.19U/ml), but no significant difference was present between them. There was no difference in the t-PA antigen content between tumor and normal renal cortex or medulla.
We studied immunohistochemical localization of u-PA by the indirect peroxidase conjugated method using antibody against human high molecular weight urokinase. Enzymatic activity was localized only in renal cell carcinoma cells, but not in necrotic tissue or interstitiall cell. The result indicates that u-PA exists in renal carcinoma cells.
In conclusion, our study suggests that the amount of u-PA antigen in urine is useful as a tumor marker for renal cell carcinoma.

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Putative neurotransmitters of the lower urinary tract were investigated in apes, rabbits and cats using immunohistochemical techniques of PAP (Peroxidase antiperoxidase) staining and IGSS (Immunogold silver staining) methods for Neuron specific enolase (NSE), Acetylcholine (Ach), Noradrenaline (NA), Vasoactive intestinal polypeptide (VIP), Substance P (SP) and Calcitonin gene related peptide (CGRP).
1) The localization of pelvic ganglions exhibited more striking evidence of species difference. Huge pelvic gangloons were found particularly in the dorsolateral area of the prostate in apes. On the other hand, in cats and rabbits, many ganglion cells were found around the uretero-vesical junctions.
2) In the pelvic ganglions of the apes, Ach immunoreactives were detected in eraly 70 percent of the cell bodies. 10-15 percent were NA immunoreactive cells. In addition, 15-20 percent VIP and a smaller percentage of SP immunoreactive cells were detected in the same ganglions. Axons extending from the ganglion cells showed the intense neurotransmitters immunoreactivity.
3) In the apes, varicose fibers containing SP were widely distributed in the epithelium, submucosa, muscle layer, and around the vessles of the bladder. SP immunoreactive cell bodies were found in the dorsal root ganglion at levels of L7, S1 and at the same levels in the posterior horn. On the other hand, the bulbourethral gland and the seminal vesicle contained SP immunoreactive cell bodies.
4) CGRP containing fibers were distributed in similar locations as SP containing fibers in the bladder.
5) VIP immunoreactive fibers were also widely distributed, being most dense at the base of the bladder.
6) Large numbers of Pacinian corpuscles were arranged in clusters at the distal site of the membranous urethra. Intense immunohistochemical reactions were demonstrated with both anti-SP and anti-VIP sera in the all outer corse. These immunohistochemical evidences suggested that the pelvic ganglion cells contained more than one potential neurotransmitter substances. It was suspected that VIP and a part of SP modulate the actions of Ach and/or NA in efferent nerve of the autonomic nervous system in the lower urinary tract. Aslo, CGRP and most of SP were considered afferent putative neurotransmitters.

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The relationship between the interval from dinner until retiring and the concentration of various substances secreted into the urine during sleep was studied in 69 healthy men who had eaten the same meal. The specific gravity and the concentrations of creatinine, uric acid and magnesium in the morning spot urine were highest in subjects who had retired within 2 hours after dinner. The concentrations of calcium and oxalate in the morning spot urine were highest in those who had retired between 2 and 4 hours. The specific gravity and urinary concentrations of creatinine, uric acid and oxalate were markedly higher in those with the interval less than 4 hours than in those 4 hours or longer. The concentrations of calcium, magnesium and citrate were not significantly different between the two groups. From these results, we recommend that the inteval from dinner until retiring be prolonged and fluid be drunk before going to bed to decrease the concentration of lithogenic substances during sleep.

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We performed partial nephrectomy in 5 patients with renal tumor. In 1 patient with synchronous bilateral renal cell carcinoma, radical nephrectomy was conducted simultaneously for the contralateral kidney. The second patient had a tranitional cell carcinoma of the renal pelvis of the contralateral side, for which the pelvis was resected simultaneously. In the remaining 3 patients the contralateral kidney was noraml. In these patients the tumor was less than 3.0cm in size and localized in either the upper pole or peripheral region, for which partial nephrectomy was performed. The weight of the resected kidney ranged 6 to 35g with a mean of 18.2g. The tumor size was 1.8 to 4.0cm, the mean being 2.4cm. Tumor grading was renal cell carcinoma grade 1 in 2 patients, grade 2 in 2 patients and oncocytoma in one patient. In all patients the tumor was encapsulated with a pseudocapsule with no involvement of the perinephric fat, venous or regional lymphnode, and the tumor was diagnosed as pT₂V₀N₀M₀, stage I. In none of the patients intraoperative or postoperative complication developed with renal function of the operated kidney normal. The follow up interval after the operation was 5 years in 1 patients and 6 months to 1 year and 2 months in the remaining 4 patients. All patients have survived without metastasis or local recurrence in the operated kidney. We believe that partial nephrectomy is worth performing in selected patients with renal cell carcinoma not only in those having lesion in solitary kidney or bilateral kidneys but also in those whose function of the contralateral kidney is normal.

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Mainz pouch procedure requires intussuscepted ileum only at the efferent limb because ureters are tunneled into the colon wall in stead of the intussuscepted ileum as done in the Kock pouch procedure. We modified the Mainz pouch procedure using the tunneled appendix as the efferent limb, in which intussuscepted ileum was no longer required. Four patients, three with bladder cancer and one with prostatic cancer, underwent this procedure. After total cystectomy and pelvic lymphadenectomy the pedicled ileocecal segment was isolated. The appendix with the intact vascular supply was separated from the ileocecal segment. After the pouch was constructed, both the ureters and the appendix were tunneled into it. The pouch was then drained by a 24Fr nephrostomy chtheter. The ureters were splinted. The pouch was closed in one layer with locked running sutures. Three patients had ureteral strictures, 2 of which were corrected by percutaneous dilatation. The third one required persistent nephrostomy drainage. The appendix of all 4 cases functioned well as the efferent limb, preventing urinary leakage and allowing easy catherterization. Three of the 4 patients satisfied with this type of urinary diversion. The modified Mainz pouch procedure may be very useful because it does not require any staples to fix the intussuscepted ileum nor a long intestinal segment. Patients whose appendix can not be utilized may be candidates for the original Mainz pouch procedure.

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This paper is the 13th report in a series of studies on the application of microexplosion to medicine and biology.
The recovery process of injured ureters was investigated in the day.
The 60 ureters of 42 mongrel dogs were used. The ureter was injured with a nail, punch or surgical knife. The “pierced injury” was passed through the ureter with a nail of 1mm or 2mm in diameter, the “punch injury” was punched out in the ureter by a punecher of 1mm or 2mm in diameter and the “cut injury” was cut in the ureter 5mm or 10mm in size with a surgical knife.
The recovery process of the injured ureter was observed in each of the two ureters 3 days, 1 week, 3 weeks, 6 weeks and 12 weeks after the injury by means of IVP, for macroscopic and microscopic findings.
The results were as follows:
1) In IVP, it was observed that the 1mm pierced injury resulted in no urine leakage after 3 days, that the 2mm pierced injury and 1mm punch injury in no urine leakage after almost 1 week and that the 2mm punch injury and 5mm cut injury and 10mm cut injury in no urine leakage after almost 3 weeks. Hydroureter due to tissue edema was observed only in one ureter with a 10mm cut injury after 1 week. No ureteral stricture, hydronephrosis or hydroureter was observed in the other ureters.
2) In macroscopic findings, urine leakage was observed similarly to IVP. A urinoma existed in 2 ureters, severe adhesion in 3 ureters, and adhesion from the plevis to the bladder in 1 ureter. Adhesion was very mild in the other ureters.
3) In microscopic findings, 3 types of recovery process were encountered in the injured ureters. In the first one, the ureter recovered primarily as transitional epithelium, which changed later to the connective tissue and muscle tissue. In the second one, the ureter was supported with surrounding tissues, and then the transitional epithelium covered the injured portion. Afterwards it proliferated as connective tissue and muscle tissue. In the third one, the ureter was closed by fibrin and the proliferated connective tissue, which changed later to muscle tissue.
Nephrostomy, stent catheterization or drainage was not employed in this experiment. From these observations the ureter is thought to be recovered primarily after injury. This suggests that a minor injury during the management of endourology for the ureter and renal pelvis, including microexplosion lithotripsy, may not result in severe complication.C

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Terbutaline and clenbuterol, which are both selective β₂-adrenoceptor agonists, produced a concentraiton-dependent decrease in contractile force of in vitro rabbit detrusor and proximal urethral smooth muscle. Conversely, terbutaline and clenbuterol produced a concentration-dependent increase in basal tension of in vitro rabbit external urethral striated muscle. Clenbuterol, oraly administrated, produced an increase in urinary bladder capacity in cystometry and also an increase in maximal urethral closure pressure in urethral pressure profile.
These results suggest that the β₂-adrenoceptor agonist may be beneficial for urinary incontinent patients.

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From 333 patients who underwent transurethral prostatectomy between May 1983 and April 1987, 123 strains of bacteria were isolated before surgery. Although all of the cocci which were sensitive to the used antimicrobials disappeared after surgery, significant difference was not observed between the disappearance rates of sensitive and non-sensitive gram-negative bacilli (disappearance rates were 86.4% and 77.8%). About two-third (34/57) of postoperative bacteria were those not isolated before surgery and patients with preoperatively infected urine had more chance than patients with sterile urine to develope infection by bacteria which was not pre-operatively detected. Precise preoperative condition is not known at the time of surgery and the sensitivity of preoperatively reported bacteria is, although important, not a sufficient information. We can only guess bacteria which might become apparent after prostatectomy.

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Thirteen evaluable patients with germinal testicular cancers failing to be cured with first-line therapy (refractory) were treated by salvage chemotherapy. Ten patients recevied salvage chemotherapy with VM-26 (50mg/m², twice a week×6 weeks) and cisplatin (CDDP, 20mg/m² for 5 consecutive days every 3 weeks for 3-4 times) (P-VM), 3 patients were also treated by radiation therapy, and 3 patients received VP-16 (100mg/m²) and CDDP (20mg/m²) (P-VP), all given daily for 5 consecutive days every 3.4 weeks for 4-5 courses.
Of 13 evaluable patients, 6 (46%) had complete response (CR) (three cases were also treated with radiation therapy), 4 (31%) achieved partial response (PR), and 3 (23%) had no response. Limited to 7 patients treated with only P-VM therapy, there were 3 (43%) CR and 4 (57%) PR. Nine patients (69%) remained alive and were continuously disease free 18 to 84 months (median 48 months). Hematologic toxcity was severe, but with no death related to sepsis. Salvage chemotherapy with VM-26 or VP-16 and cisplatine offers potentially curative treatment to patients with refratory testicular cancer. The addition of radiation therapy to salvage chemotherapy was also effective.

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Pancreas carcinoma is sometimes notoriously difficult to diagnose. Although it is well known that pancreas carcinoma can invade contiguous organs, no attention to urinary tract involvement is paid. Although urinaly tract is involved at a late stage, it may represent the first symptomatic evidence of the disease. In such cases, pancreas carcinoma can be presented initially as a urologic disease and patients' symptom may not be differentiated from urinary tract diseases.
Computed tomographic (CT) images and medical records of 50 patients with histologically proved pancreas carcinoma were reviewed. There were 10 cases with urinary tract involvement. IVP study was performed in 8 of these cases. Of the 10 cases 8 were male and 2 were female. There was a high incidence of left urinary tract involvement (left:right:bilateral=7:2:1). Nine cases were pancreas body and tail carcinoma and 1 case was pancreas head carcinoma. The stages were all in IV. All cases were with confirmed evidence of urinary tract involvement at autopsy within 4 months following CT studies. We compaired those IVP, CT images and findings of autopsy. In these patients, 4 cases showed direct invasion of the kidney, 5 cases ureteral involvement and 1 case metastasis to the urinary bladder and ureters.
IVP showed inferior displacement of the kidney and/or ureteral displacement on the affected side, as well as collecting system distortion, including hydronephrosis secondary to ureteral compression.
CT scan showed an abnormal mass which is contiguous to the pancreas, showing compression of the kidney and/or retroperitoneal extension with ureteral involvement. Metastasis to the urinary bladder is also identified. The findings of autopsy were almost the same as the CT findings.
Pancreas carcinoma characteristically remains silent until it reaches the stage when there is little chance for cure. Although urinary tract involvement is rare, it can mimic renal and ureteral pathology. The radiologist and urologist must include, in the differential diagnosis of urinary tract lesion, disease process originating in the pancreas and its contiguous structure.

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N-acetyl-β-D-glucosaminidase from human seminal plasma has been separated by the cellulose acetate electrophoresis into two components, isoenzyme I and II. The two isoenzyme are readily separated on a DEAE-Sephadex column. Isoenzyme I which has adsorbed to the column, is eluted at 0.1M NaCl, whereas isoenzyme II has passed through the column.
The following enzyme properties have been obtained: 1) Both isoenzymes show the same Km values (0.27×10^-3M) towards sodio-m-cresol-sufonphtaleinyl-N-acetyl-β-D-glucosaminide. 2) Both isoenzymes show the same pH optima of 5.4. 3) Optimal temperature for isoenzyme I is 50°C, while that for isoenzyme II is 65°C. Isoenzyme II is heat stable, while isoenzyme I is easily denatured by heat. These characteristics of isoenzyme I and II coincide with previous reports of NAG A and B from the spleen and the kidney, respectively.
The activity ratio of isoenzyme I and II has been studied for the reproductive tissues. The % ratio of isoenxyme I and II in the epididymal head is 62 and 38, that in the epididymal tail is 42 and 58, and 38:62 in the seminal vesicle, 35:65 in the prostatic gland and 27:73 in the seminal plasma.

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During the period from July 1975 to September 1987, 325 patients with bladder tumor were treated in Kinki University. 152 of them were treated by total cystourethrectomy. On these 152 cases clinical assessment was performed from several aspects.
The 152 patients consisted of 111 males and 41 females. The overall mean age was 64.6 years old. Tumor with the grade G1 was found in 14 patients, G2 in 65 and G3 in 73. As for the stage, CIS was seen in 21 patients, T1 in 60, T2 in 22, T3_a in 23, T3_b in 15 and T4 in 11.
The 5 year survival rate of the total patients was 62%. The rate by grade was 78% in G1, 66% in G2 and 55% in G3; the rate by stage was 75% in CIS, 77% in T1, 59% in T2, 57% in T3_a, 36% in T3_b and 13% in T4. When the stage became T3_b, the survival rate fell remarkbly.
Lymphadenectomy was performed in 136 of the 152 patients and metastasis was observed in 19 patients of the former. Their 5 year survival rate was 22% in patients with lymphnode involvement and 70% in those without lymphnode involvement; the difference was significant.
Furthermore, the relation between the macroscopic appearance and the survival rate was studied. The size, multiplicity and growth pattern (papillary or nodular) were likely to be related to the survival rate of bladder tumors.
We believe that these clinical assessments for bladder tumors will contribute to an improvement of the therapeutic results for the tumors together with studies on their natural history.

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The effect of furosemide on the obstructed kidney was studied in dogs. In control kidneys (n=4) the renal blood flow (RBF) was increased transiently after intravenous infusion of 20mg of furosemide; from 12.9±1.2 to 14.8±1.4ml/min/kg. B. W.. No change in the renal pelvic pressure was observed. Urine flow increased from 0.47±0.12 to 4.98±1.15ml/min at 20 minutes after furosemide administration. Increases, in the fractional fluid excretin rate (V/GFR), the fractional sodium excretion rate (FENa) and the fractional potassium excretion rate (FEK) were observed and the maximum values were obtained at 20 minutes after furosemide administration.
In two-week unilateral incompletely obstructed kidneys (incomplete UUO; n=5), RBF was lower than that of the control kidney, whereas a tendency of transient increase was also noticed after furosemide administration; from 8.4±1.9 to 10.5±2.3ml/min/kg. B. W.. The renal pelvic pressure increased immediately and transiently after furosemide infusion. Increase in the urine flow was significant, but the value was lower than that of control, and the maximum value was marked at 20 minutes after furosemide administration. V/GFR, FENa and FEK were also increased in incomplete UUO, but the peak values were lower than those of control.
In two-week unilateral completely obstructed kidneys (complete UUO; n=5), RBF was markedly decreased (3.14±0.38ml/min/kg. B. W.), and no significant increase was noticed after furosemide administration. The renal pelvic pressure was gradually and continuously increased after furosemide infusion. The fractional excretion rate of pelvic urine components was variable. In particular, V/GFR was significantly increased 60 minutes after furosemide administration.
These results indicate that the obstructed kidney may respond to furosemide, and the time necessary for diuretic effect is the same as in the normal kidney. While the response level is low, probably because the secretion of furosemide from the proximal tublues is decreased in the obstructed kidney due to the decreased renal blood flow.

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Total of 37 patients with measurable lesions originating in advanced urothelial cancers received M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) combination chemotherapy and have been followed for a minimum of 12 months.
The study included initial diagnoses of 24 bladder cancers and 13 upper urinary tract cancers in patients whose mean age was 62 years. The patients received a maen of three cycles of M-VAC. Clinical complete remission was observed in five of the 37 patients (13.5%) and partial remission was achieved in 10 patients (27.0%) after mean treatment of 2.4 and 2.1 cycles, respectively, for an over-all objective response rate of 40.5%. The mean duration of response was 11.6±7.1 months and 4.4±3.5 months for complete and partial remissions, respectively.
A mean of 5.2±1.7 cycles of M-VAC was given for complete remissions and 3.5±1.4 cycles in partial remissions. An over-all survival rates after one and two years were 28.125% and 5.859%, respectively. Two of the five patients who had once marked complete remissions died after a mean survival time of 14.5±4.5 months and three survived with a mean duration of 20.3±5.4 months. Meanwhile, all of the piatents who had achieved partial remissions died after a mean survival of 9.1±5.4 months except for one patient who survived more than 12 months.
These results indicate that M-VAC combination chemotherapy for advanced urothelial cancer is extremely efficacious in initial responses. However, significant toxicities necessitated delay or discontinuance of the treatment, and the appearance of strains resistant to these chemotherapeutic agents must be considered in patients who have been repeatedly treated. Therefore, further investigations should be directed toward solution of these problems to improve the long-term results.

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As an approach to develop a new therapeutic modality for testicular germ cell tumor, in vitro studies were performed to investigate the capacity of testicular choriocarcinoma cell line JHTK-1 to differentiate and to screen its differentiation inducing substances.
We have found that dibutyryl cyclic adenosine monophosphate (DBcAMP) induces multiple phenotypic changes of JHTK-1 cells within 48hr, i. e., morphological alteration, enhancement of human chorionic gonadotropin (HCG) production, and inhibition of the cellular proliferation. Upon addition of 1mM DBcAMP to the culture mediums, broad and elongated cells with cytoplasmic projections, increased secretion of HCG to the culure mediums more than 15-fold and increased number of HCG positive cells more than 10-fold in immuno-histochemical study, and inhibition of cell proliferation more than 50 percent were seen. The changes were dose dependent as to DBcAMP.
These results indicate that DBcAMP induces the differentiation of testicular choriocarcinoma cells from dividing cytotrophoblastic cells to non-dividing end cells of syncytio-trophoblastic cells.
Screening of differentiation inducing substances were carried out using an increase in HCG secretion/cell/48hr as an indicator of JHTK-1 cell differentiation. The inducers were theophylline, sodium butyrate, N-butyrate, vitamin C, vinblastine, and actinomycin D.
In conclusion external stimuli such as chemical substances can induce the differentiation of testicular choriocarcinoma cells, and inhibit their cellular prliferation as well. This finding will lead to a concept of “differentiation induction therapy” for testicular choriocarcinoma.

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A 76-year-old woman presented with a history of pain on urination and urinary frequency. The sonogram incidentally demonstrated a mass in the area of the upper right kidney, and CT scan revealed a retroperitoneal tumor.
Operation was carried out, and the tumor measured 4×4×5.5cm (35g). The pathology report was consistent with leiomyoma. The patient had undergone surgical excision of a right retroperitoneal tumor before 27 years, and it is suspected to have been an ectopic retroperitoneal tumor judging from operative findings. Retroperitoneal leiomyoma is rare and a review of the Japanese litarature is presented.

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Two cases of ectopic prostatic tissue or adenomatous polyps with prostatic type epithelium in the prostatic urethra were reported. They were 30-and 33-year-old males suffering from gross-hematuria and from urethral pain on urination with terminal gross-hematuria. Endoscopic examination revealed papillary lesions from the dilated orifice of the prostatic utricle. Biopsied pathology demonstrated a tissue similar to that of the prostatic gland. PSA (prostatic specific antigen) stain using immunohistochemical methods was positive. Histogenesis and the importance of this lesion particularly as a cause of hematuria in the young male adult were discussed.

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