For the first time in Japan, we have treated renal and upper ureteral stones using ESWL since September 1st 1984. The results have been satisfactory. We present our experience with ESWL.
We have treated 101 cases of renal and upper ureteral stones in 107 treatments. In 90% of these patients epidural anasthesia was used. The ages of the cases ranged from 20 to 74 years old, including 30 cases of women and 71 cases of men. The size of the stones varied from less than 1cm to staghorn calculi. To break up these stones, 400 to 2200 shock waves were necessary. In 80 cases (79%) less than 1500 shock waves were used. The treatments lasted from 7 to 60 minutes with the average time from 11 to 40 minutes (86%).
76% of all cases had spontaneous sandy stone passage without complain. But 24% had such symptoms as fever and/or pain. 5 cases experienced dull pain or fever due to stone fragments that filled the lower ureter after distingrating large stones. Ureteral meatotomy in such cases produced satisfactory results. None of these patients needed open operation.
In 99% of the cases the size of the discharged stone fragments was less than 2mm. Although our observation of the patients was still short we found natural discharge of stone fragments after ESWL treatment in 47 cases. The other cases had only sandy stones that easily discharged. Analysis of the stones showed that 82% were composed of caoxalate. Besides caoxalate 2 cases were composed off urate, 1 case was composed of cystine.
From these present findings, it appears that ESWL can break all stones of any size, composition, and the number of stones. The important thing for the future is how to facilitate the discharge of stone fragments after ESWL treatment.
We are confident that ESWL will soon take the place of surgery in treating urinary tract calculi.

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The cross-reactivity between Streptococcal cells and tumors was studied by the immunohistochemistry (peroxidase anti-peroxidase: PAP method). Both anti-Streptococcus (Su strain) antibody and anti-rat bladder tumor (BC-47) antibody reacted with either BC-47 or Streptococcus preparation, OK-432, by the PAP method. The specificity of the PAP reaction using anti-Su or anti-BC-47 serum was confirmed by the absorption study of the first antibody, mentioned above, with the homoand heterologous antigens. The anti-Su antibody did not react with the normal rat tissues except for in the renal tubules, epidermis and sweat glands. Furthermore, anti-Su serum showed the positive PAP reaction in three kinds of tumors, mouse sarcoma Meth-A, mouse sarcoma S-180 and Ehrlich carcinoma, but it did not show the reaction in mouse adenocarcinoma Ca. 755, Waker 256 adenocarcinoma and mouse leukemia P-388. It had already been reported and confirmed that the growth of four kinds of tumors, BC-47, Meth-A, S-180 and Ehrlich carcinoma, which showed the positive PAP reaction, were remarkably inhibited by OK-432, and that other three kinds of tumors which showed the negative PAP reaction were non-effective with OK-432. The PAP examinations in which anti-group A specific C-polysaccharide and anti-group A specific antibody were used showed the same results as did the anti-Su serum. The cross-reactivity between cells of OK-432 and human urological carcinoma was investigated by the PAP method using anti-Su serum, as animal tumors were. Thus antigenic cross-reactivity was also shown between cells of Streptococcus and many kinds of tumors in both animals and humans. It is suggested that the common antigen would be the group A specific C-polysaccharide (Rhamnose-N-acetyl glucosamine polysaccharide) and this common antigen could induce the tumor specific immune response involved in either killer T cells or antibody dependent cell mediated cytotoxicity (ADCC), and then promote tumor regression.

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Cis-diamminedichloroplatinum (II) has a marked anti-cancer effect on advanced urogenital neoplasm. However, its nephrotoxicity has been hindering the therapeutic usefulness of this drug. Reduction of acute nephrotoxicity has been achieved by use of pretreatment hydration and mannitol or furosemide diuresis. On the other hand, patients with urogenital neoplasm have many urinary tract complications, such as solitary kidney, various urinary diversion, hydronephrosis and pyelonephritis. Despite these hydration and diuresis, considerable deterioration of renal function occurs in those patients after CDDP treatment.
Renal function in 17 patients with advanced urogenital neoplasm treated with the regimens including CDDP was evaluated retrospectively. Four (23.5%) of the 17 patients showed renal dysfunction during the treatment.
Our study was designed to estimate the values urinary, β₂-microglobulin (β₂MG) and N-acetyl-β-glucosaminidase (NAG) excretion and the fractional excretion of sodium (FE_Na) as a sensitive indicator for prediction and early detection of CDDP nephrotoxicity.
In urogenital cancer patients, NAG and β₂MG excretions rose markedly in early stage of the CDDP treatment. In only one patient that fell into progressive renal insufficiency, extremely high levels of β₂MG and NAG excretions (β₂MG: 21090μg/day, NAG: 44.3unit/day) were noted compared with other patients.
Urinary excretion and renal tissue concentration of NAG were also studied in rat CDDP nephrotoxicity. Each of the rats that received CDDP at a dose of 2, 4 or 8mg/kg/day revealed significantly high urinary NAG excretion in comparison with the control (p<0.05). The NAG concentration in the renal tissue decreased contrarily to the CDDP concentration.
FE_Na is generally considered more helpful than other conventional methods in evaluating renal function in acute renal failure.
Both animal experiments and clinical studies showed that an elevated FE_Na was noted in CDDP induced acute tubular injury.
Furthermore, the patients with deterioration of renal function after the CDDP treatment revealed higher pretreatment levels of FE_Na compared with those showing no renal dysfunction.
It is concluded that the values of FE_Na and urinary N-acetyl-β-glucosaminidase and β₂-microglobulin excretions are sensitive indicators for the early detection of acute tubular damage induced by CDDP.

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The majority of reports hitherto concerning the drug-resistance factor in Serratia marcescens deal only with the detection of transferable plasmids through conjugal transfer, and practically no reports have appeared that have investigated down at the DNA level, whereby DNA is extracted and non-transferable plasmids are detected after transformation. Consequently, as part of our study into drug resistance, the resistance type of 99 clinically-isolated strains of Serratia marcescens was investigated. Further, transferable and non-transferable plasmids were examined in resistant strains, and the plasmid DNA was confirmed using agarose gel electrophoresis. In particular, amongst the various drugresistance plasmids, the PC-resistance was investigated by examining the type of β-lactamase produced from substrate specificity.
As a result, resistance to TC, CER and ABPC were not considered to be the intrinsic resistance of Serratia marcescens, especially in the case of ABPC whereby resistance plasmids occurred at a high frequency.
Transferable plasmids are divided into three groups according to the test facility and the period of isolation: group A (control group; isolated during March, 1979 to February, 1980), group B₁ (former group; isolated during June, 1980 to July, 1980), and group B₂ (latter group; isolated during August, 1980 to December, 1980). The ABPC and KM resistance type plasmids were most frequently observed in the A and B₁ groups, whilst, in group B₂ SM, SA, ABPC and KM, resistance type plasmids occurred at a high frequency. These were considered to be epidemic plasmids that changed rapidly in a short period of time.
Moreover, the results suggest that non-transferable plasmids assume transferability, and that not only transferable but also non-transferable plasmids are clinically important.

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Twenty-one patients underwent one-stage hypospadias repair by Hodgson type III procedure. Thirteen patients healed without any complications. Four patients developed minor complications. Taken together, seventeen patients (81%) have got almost satisfactory rehabilitaion. These experiences suggest the following:
1. An inverted V shape incision of the dorsal preputial skin is useful to repair the skin defect.
2. Our attention has been focused on the adequate release of chordee and the construction of the appropriate sized neourethra. Intraoperative artificial erection technique is useful in order to confirm the completion of chordectomy and to decide the length of the neourethra. The size of island skin flap should be designed as small as possible just to fulfill the minimum requirement.
3. The uroflowmetry is a simple and non-invasive procedure which provides an objective evaluation of the urinary stream.
However, major complications developed in four cases (19%). Fistula formation occurred in two cases and urethral stricture at the anastmotic site developed in the other two cases.

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From September, 1973 to October, 1984, 103 living related and 1 living unrelated kidney transplantations were performed on 103 patients with end stage renal failure. Five of the 103 recipients were transplanted from HLA two haploidentical donors and 97 from HLA one haploidentical donors. 102 recipients received primary grafts and 2 secondary grafts. 87 of the 103 recipients had a history of pretransplant blood transfusion.
The recipient and the allograft survival rates in the entired series were 95.7% & 80.5%, respectively, at 1 year, 85.0% & 67.9% at 3 years, 78.1% & 56.2% at 5 years and 71.8% & 50.6% at 10 years.
Of 97 recipients with kidneys from HLA one haploidentical donors, the first 20 received standard immunosuppression with steroid and azathioprine. The next 42 received short term ALG in addition to the standard immunosuppression. In these 42 recipients, rejection episodes were treated with low doses of steroid. Of the third 42 recipients, 33 received thoracic duct drainage pretreatment and the standard immunosuppression, and 9 received new immunosuppression with cyclosporine and steroid.
From the results observed in these three groups, it was indicated that (1) a low dose of steroid treatment for rejection resulted in a trend towards improved recipients' survival without sacrifing kidney graft survival. (2) the TDD pretreatment yieled beneficial effects on graft survival.

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Fifty-five patients with testicular tumors were treated surgically (high orchiectomy) in combination with radiotherapy alone, radiotherapy with chemotherapy, or chemotherapy alone. Thirty-one of them had seminomas and radiotherapy was delivered to 29 patients as a single adjuvant treatment and to one in combination with CDDP. CDDP alone was given to one patient as an adjuvant therapy. Four patients with M1 died of the disease. In one patient, T2N3M0, with subsequent distant metastases in the tonsil, cerebellum and lung, radiotherapy was so effective as to prolong his survival for 7.4 years since his initial visit and complete remission lasted for four years after the last treatment. Twenty patients with nonseminomatous tumors were managed by radiotherapy and chemotherapy. According the our recent chemotherapeutic schedule, nine of them were treated with CDDP. Six patients with either N3 or M1 died of the disease. of 11 patients who underwent chemotherapy including CDDP, tumor markers in seven patients became normal, partial remission was obtained in one, and three died of the disease. One patient (case no. 1) remains CR for 6.4 years since his initial visit. Toxicity of chemotherapy consisted of nausea or vomiting in all patients, marked anemia necessitating blood replacement in two, and shock in one patient who became intolerable to further chemotherapy.
CDDP was administered in doses of 30-50mg/m², i. v., qW, for 10 weeks as an initial treatment and then tapered to q1 or 2 months for two years as a long term chemotherapy. The patients were hydrated by d. i. v. transfusion of 2500ml fluid on the first day and CDDP with an antimimetic agent was given, i. v., when 500ml of the fluid had been given. A diuretic drug was added 30min later.

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We evaluated the enzyme immunoassay kit of γ-Seminoprotein (γ-Sm) that has been identified and purified from human seminal plasma by M. Hara for the diagnosis of prostatic cancer. The level of γ-Sm in the serum was measured using this kit in patients with untreated prostatic cancer (confirmed pathologically), benign prostate hypertrophy and other urological diseases.
Although there was no statistical difference in γ-Sm levels between the stage A prostatic cancer group and benign prostate hypertrophy group, stage B, C and D prostatic cancer exhibited its benign prostate hypertrophy. The sensitivity of the test among total prostate cancer patients was about 70%, but there was no distinct correlation between γ-Sm and PAP.
These results suggest that γ-Sm is a new valuable marker for diagnosis of prostatic cancer.

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The presence of mast cells, eosinophils and round cells was studied to investigate the participation of I type allergy in interstitial cystitis. Six subjects were examined: 3 cases were diagnosed clinicalallergologically to be dependent on allergy, and in the other 3 cases with a severely contracted bladder, the participation of allergy had not been confirmed up to the time of examination. The amounts of mastcells were in various degrees from nothing to moderate in 15 cases of various kinds of cystitis other than interstitial cystitis, while the amounts of eosinophils were less than mild in all 15 cases. In 3 cases of interstitial cystitis diagnosed clinically to be dependent on allergy, the amounts of mast cells and eosinophils were in higher than moderate degrees and the amounts of round cells were in lower than moderate degrees. In 3 cases of interstitial cystitis with a severely contracted bladder in which the participation of allergy had not been confirmed by then, the amounts of round cells were in higher than moderate degrees but the amounts of mast cells and eosinophiles were also in higher than moderate. These results showed that there were requirements for inducing I type allergic reaction in interstitial cystitis, and suggested the participation of I type allergy also in 3 cases of interstitial cystitis in which the participation of allergy had not been confirmed up to the time of examination.

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A method for enzymatic determination of urinary citrate using citrate lyase is described. The optimum pH is 7.2 and the addition of zinc ion is found to activate the reaction, but the influence of pH and zinc ion on the reaction velocity is reduced in proportion to increase of citrate lyase. The effect of the Tris HCl buffer concentration on reaction velocity is also studied, and high concentrations of the Tris HCl buffer are found to inhibit the reaction.
The recovery rates of citrate added to urine ranged from 98.5% to 103% and the coefficient of variation of triplicate assay is 3.1%.
The urinary citrate excretion in healthy volunteers are 397±159 and 474±209mg/day (mean±SD) for 66 males and 23 females, respectively.
Since this method is highly precise and convenient, it may be readily adopted as a routine clinical examination.

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X-ray fluoroscopic cystometry (CG-CM) was carried out on 12 cases of pediatric vesicoureteral reflux (VUR) including 7 cases of non-obstructive VUR and 5 cases of neurogenic bladder (total 18 reters). The following results were obtained.
1) The classification of VUR with CG-CM in the past reports was not based on analyses of cystometrogram (CMG) and not suitable for actual cases. A new classification to follow was proposed: Type I (low pressure reflux) during the resting pressure on CMG, Type II (high pressure reflux) at the voiding reflex and Type III (high pressure reflux) at the voluntary voiding with abdominal pressure.
2) The average intravesical pressure at the initiation of VUR was 25.6 mmHg in Type I, 41.4mmHg in Type II and 86.3mmHg in Type III. The average vesical capacity in the same period was 387.9ml in Type I, 245.6ml in Type II and 53.3ml in Type III. Non-obstructive VUR tended to have a large vesical capacity, while neurogenic bladder a smaller one.
3) Grading at the initiation of VUR with this study differed from the one with one-shot cystogram or voiding cystourethrogram which had been performed for the screening. There remains the problem what the real grade of VUR is in the process of occurrence of VUR. Functional grading including timing of VUR, however, is prossible with CG-CM.
4) Comparing the grade of VUR with that of hydronephrosis on respective type of VUR, both parameters were coincident in Type I. However, there was dissociation of them in Type II and Type III: the grade of hydronephrosis tended to be milder than that of VUR.
5) In relation of respective type of VUR to CMG, normal pattern or flaccid bladder was found in most of Type I, the number of spastic bladder or uninhibited bladder, however, increased in Types II and III.
6) The ultimate aim of this study is to determine the therapeutic policy for pediatric VUR. Although distinct conclusions were not drawn from this study due to the paucity of clinical cases, the following tendency was recognized. Course observation should be adopted in the low grade VUR of Type I, while surgical therapy would be necessary in the high grade one and the percentage of conservative therapy increased in Types II and III.

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Inorder to clarify the role of macrophages (Mφ) in the host defense mechanism in rats with P. mirabilis pyelonephritis, the superoxide (O₂^-)-releasing activity of peritoneal Mφ, the severity of the pyelonephritis and the rate of fatal infection were examined under various conditions which modified the host defense mechanism.
For modification of the host defense mechanism, OK-432 (50KE/kg), cyclophosphamide (100mg/kg), diethylstilbestrol (200mg/kg) and carrageenan (200mg/kg) were used as a nonpsecific immunoactivator, nonspecific immunosuppressor, activator of Mφ and suppressor of Mφ, respectively.
The results were as follows:
1) The O₂^--relesing activity of peritoneal Mφ 7 days after the inoculation of P. mirabilis into the bladder was definitely higher than that of normal rats.
2) The O₂^--releasing activity of peritoneal Mφ was definitely or relatively increased when the activator of Mφ (diethylstilbestrol) or the immunoactivator (OK432) was used, but definitely decreased when the immunosuppressor (cyclophosphamide) or suppressor of Mφ (carrageenan) was used.
However, the severity of pyelonephritis and fatal infection rate were decreased only when the OK432 was used, and there was no difference in the items between the controls and the rats in which cyclophosphamide, dietylstilbestrol or carrageenan was used.
These results suggest that Mφ are activated by infection with P. mirabilis but that they play an adjunctive role in protection against infection.

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The usefulness of Matsumoto's endoscopic classification of urinary bladder tumor was evaluated to compare with cellular gradings, cellular thickness, cell surface appearance by scanning electron microscopy (SEM) and clinical course. Bladder tumors from 35 patients (26 men and 9 women) were examined. They were divided into 14 cases of bush type, 16 cases of grapes type and 5 cases of knoll type, according to Matsumoto's endoscopic classification (Proc. of Ann. Meeting of Jpn. Urol. Ass., 1983, p. 61). Bush type consisted of 43 percents of grade 1, 57 percents of grade 2 and none of grade 3. Grapes type consisted of 25 percents of grade 1, 63 percents of grade 2 and 13 percents of grade 3. Knoll type was all grade 3. No significant difference between bush and grapes types was found in thickness of tumor cell layer, but for knoll type the thickness could not be measured because of cellular disorder. Surface features of superficial tumor cells in bush and grapes types by SEM (Jpn. J. Urol., 73; 469, 1982) showed pleomorphic microvilli but the plemorphism of grapes type was higher than that of bush type. Knoll type showed smooth or rough surface. Bush and grapes types showed no difference of tumor recurrence, but some cases of grapes types became invasive. Eighty percents of knoll type was invasive and all of knoll type underwent total cystectomy. It is concluded that cellular gradings, cellular thickness and cell surface appearance by SEM had relatively good corellation with Matsumoto's endoscopic classification. However, these studies suggest that further examination of this problem must be done.

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Clinical study of the bladder tumor was attempted to elucidate the prognostic factor and appropriate operation, bases on the 416 cases experienced in our department for the past twelve years. As far as the clinical staging was concerned, tumors were divided into low stage and high stage. As to the tumor grade and histological type, they were also classified as low grade and high grade. The parallel relationship could be found between tumor stage and tumor grade, while there were moderate numbers of cases with low stage-high grade or high stage-low grade.
Regarding as survival rate, five years survival rates of low stage and low grade groups were significantly higher than those of high stage and high grade groups, respectively. Five years survival rates of both low stage-high grade and high stage-low grade groups showed no significant difference. The cancer death rate of low stage-high grade group was almost the same as that of high stage-low grade one.
The analysis of cancer therapy clarified as follows: (1) Low stage-low grade group could be controlled by bladder preservation-therapy including TUR-bt. (2) Low stage-high grade cases were often necessary to undergo total cystectomy. (3) High stage-low grade group would be managed by radical cystectomy. (4) The treatment for high stage-high grade tumor should be performed by radical cystectomy, because the rate of cancer death in TUR cases was unacceptablly high.

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We have previously reported that the excretion of urinary γ-carboxyglutamic acid (Gla) in calcium stone formers was lower than that in healthy adults. However, it has not yet been clarified whether this is caused by inhibitory actions of Gla on calcium stone formation or Gla is only adsorbed on the surface of stones.
In order to clarify this point, we compared the urinary Gla-excretion in the presence and absence of calcium stones. Moreover, also investigated the urinary Gla-excretion before and after ingestion of low calcium diet or administering thiazide in patients with idiopathic hypercalciuria to observe how Gla-excretion varies with changes of the urinary Gla-excretion.
In the presence of stones, urinary Gla-excretion was 38.3±8.6μmol/day in males (12 patients) and 30.7±5.3μmol/day in females (7 patients). After extripation of the stones, it increased to 42.2±5.7μmol/day in males and to 39.5±7.0μmol/day with a significant difference (p<0.001) in females.
In the case of ingestion of low calcium diet, the values before and after ingestion were 39.5±8.6μmol/day and 41.6±7.3μmol/day, respectively, in males (17 patients), and 34.5±7.8μmol/day and 37.0±4.4μmol/day, respectively, in females (6 patients), without significant difference.
In the case of administration of thiazide, the values before and after administration were 40.9±7.1μmol/day and 45.2±7.5μmol/day in males (11 patiens), and 38.2±7.2μmol/day and 36.7±6.5μmol/day in females (10 patients), respectively, without significant difference.
From the above results, we inferred that decrease in the urinary Gla-excretion was caused by the action that urinary Gla is adsorbed on the surface of stones independent of changes of the urinary calcium-excretion.

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We studied the effect of vitamin D₃ compounds on the growth of the human renal carcinoma cell lines, KU-2 and Caki-1, and discovered a receptor protein specific for the active form of vitamin D₃, 1α, 25-dihydroxyvitamin D₃ in the cytosol of these cells. Vitamin D₃ derivatives dose-dependently suppressed proliferation of these cells in a monolayer culture and also suppressed their clonogenicity in a soft agar culture. Radioreceptor assay and sucrose density gradient analysis showed that these two cell lines contained a 3.2S receptor protein to which 1α, 25-dihydroxyvitamin D₃ was specifically bound and which is identical to the receptor in the normal tissues reported previously. The binding capacity was 87fmol/mg protein in the KU-2 cells and was 17fmol/mg protein in the Caki-1 cells. Of the vitamin D derivatives tested, 1α, 25-dihydroxyvitamin D₃ was the most potent in inhibiting KU-2 cell growth, followed by 1α, 24R, 25-trihydroxyvitamin D₃, 25-hydroxyvitamin D₃, 1α-hydroxyvitamin D₃ and 24R, 25-dihydroxyvitamin D₃ in this order. The affinity of various vitamin D₃ derivatives to the KU-2 cytosol receptors was closely related to the abiliry to inhibit growth of the cells. These results indicate that the effects of vitamin D₃ derivatives in inhibiting proliferation and clonogenicity of the cell lines are mediated by the receptor, and that the active form of vitamin D may be one of the regulatory factors affecting the proliferation and other biological functions of renal cell carcinoma.

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A rare case who represented complete regression of pulmonary metastases from renal cell carcinoma induced by medroxyprogesterone acetate (Provera^®) and streptococcal preparation (OK-432) is presented.
A 59-year-old man with hemosputum and weight loss was radiographically found to have left renal tumor metastasized to the both lungs and the left adrenal. He underwent radical nephrectomy and was treated with administration of OK-432 and Provera as an adjuvant. Pathological diagnosis of the tumor was alveolar type renal cell carcinoma mainly consisting of clear cells with adrenal metastasis. Transbronchial lung biopsy showed that the pulmonary lesions were metastatic carcinoma. A month after the beginning of oral administration of Provera, 100mg daily, the pulmonary lesions began to regress. A subsequent chest X-P taken 1.5 months later showed complete disappearance of the coin lesions. He had 16 week and additional 8 week administrations of Provera, supplemented with intramuscular OK-432, 5KE/week. At present, 1 year after the nephrectomy, all of laboratory and clinical findings show that he is free from the disease and he is doing as well as he used to be.

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A 58-year-old man with a chief complaint of dysuria was reffered to us in June, 1982.
Two bladder tumors were revealed by urethrocystoscopy.
A thumb finger tip sized tumor was located at the dome and another red bean sized tumor was located at the trigone of the bladder.
From the histological findings of the specimens obtained by transurethral resection of bladder tumors, the large one was suspected to be a malignant fibrous histiocytoma (MFH) and the small one an inverted papilloma. Therefore, partial cystectomy was done for the large tumor. Histological diangosis of the large tumor at the dome was MFH of the bladder.
As adjunctive treatment, the patient received chemoimmunotherapy with vincristine, peplomycin, adrianycin and OK-432 combined with radiation therapy. No recurrence and metastasis have been located in 28 months after operation.
We reviewed MFH of urogenital organs in Japan.

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