[in Japanese]

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Ultrasonotomograms of 22 kidneys were obtained in 11 patients with renal-acute renal failure (renal-ARF). The underlying diseases of renal-ARF were acute tubular necrosis in 8 patients and acute on-set chronic glomerulonephritis in 3 patients. They were treated by hemodialysis in 10 patients and intermittent peritoneal dialysis in 1 patient.
Ultrasonic measurement of the size of kidneys revealed that the thickness (anterior-posterior diameter) and the ratio of thickness to length (T/L) were greater in patients with ARF than in those with chronic renal failure and normal renal function. The patients with a low value of T/L (under 0.60) had a significantly greater urine volume than those with high a value of T/L (0.60 or more).
The sonographic features of renal-ARF kidneys were marked increase in parenchymal echogenicity and appearance of hypoechoic swollen renal pyramids with sharpssne of the corticomedullary border. In the course of ARF, these sonographic changes gradually disappeared when the patients had recovered from ARF. However, the prognosis was poor in patients with severer sonographic findings.
We believe that repeated ultrasonic examination of the kidneys in patients with renal-ARF is useful for not only differential diagnosis of post-renal urinary obstruction but evaluating the course of ARF.

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Clinical results of ESWL for renal and ureteral stone with MPL-9000 were presented. We also reviewed correlation between stone burdne and shock wave energy. We studide 210 cases (295 sessions) of renal stone and 109 cases (154 sessions) of ureteral stone that were treated from November 1988 till January 1989 and from November 1989 till May 1990. Of those sessions, 76 sessions of renal stone cases and 53 of ureteral stone cases were carried out ambulatorily. Successful disintegration (within 4mm) rate was 86% of renal stones, 84% of ureteral stones, and stone free rate after 6 months was 72% of renal stones and 84% of ureteral stones. As for the complications, brain infarction occurred in one case, subcapsular hematoma of the kidney in one, and arythmia in 5. No other severe side effects were observed.
Between shock wave energy (the number of shock wave shots×voltage) and stone burden (long axis×short axis of the stone), a significant correlation was found in renal stone cases, but not in ureteral stone cases. E/B (shock wave energy/stone burden) was 33100 (kv·shots/cm²) for the renal stone and 56000 (kv·shots/cm²) for the ureteral stone. These results suggest that there is still another unknown factor, which is not related with renal stone, for successful disintegration of ureteral stone. We also confirmed that more energy is necessary for destruction of ureteral stone than for that of renal stone.
It was proved that we could perform ESWL with MPL-9000 safe by without hospitalization for selected cases, although the indication and selection of the auxiliary procedures might be important for ESWL of large renal stones and ureteral stones impacted for a long time.

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Pre- and post-operative changes of renal function in twenty children (10 were younger than 2 years old) with unilateral hydronephrosis due to ureteropelvic junction obstruction were studied on the basis of DMSA renal uptake rate.
A marked increase in DMSA renal uptake rate was observed in thirteen cases (65%) after pyeloplasty on the obstructed side. Among them eight children were younger than 2 years old.
In 6 children younger than 2 years old, a remarkable increase of DMSA renal uptake rate after reconstructive operation was recognized not only on the obstructed side but also on the contralateral normal side. These tendency could not be observed in those older than 2 years old. These results suggest that, in the young children, the obstructed kidney inhibits the contralateral normal and compensatory renal growth, and that the relief of obstruction eliminates this inhibition and causes the renal growth spur in a normal kidney.
We conclude that it is essential to correct unilateral ureteropelvic junction obstruction before two years of age if an improvement of renal function not only on the obstructed side but also on the normal side is to be expected.

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Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6Gy over 3 weeks)prior to a planned cystectomy.
Cisplatin, in total 200mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef. 3 in 1 case, Ef. 2 in 6. Ef. 1b in 1 and Ef. 1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there was no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated.

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From 1984 to 1990, ^99mTc-DMSA renal scintigraphy was performed before and after nephrolithotomy (15 cases), pyelolithotomy (15 cases), percutaneous nephrolithotripsy (PNL: 15 cases) and extracorporeal shock wave lithotripsy (ESWL: 16 cases, 17 kidneys) in order to evaluate of influences of renal stone surgeries on split renal function. DMSA renal uptake change ratio of treated kidneys of nephrolithotomy (-24.94±5.60%) was significantly lower than that of PNL (-0.06±3.92%), pyelolithotomy (-4.08±4.79%) (p<0.01) and ESWL (-7.72±3.87%) (p<0.05). The average change ratios of contralateral kidneys were as follows: PNL 4.80±4.21% nephrolithotomy 4.67±4.73%, pyelolithotomy -1.46±5.39% and ESWL -2.02±4.44%.
One to 3 weeks after PNL, the cold area on the renal image was found in 10 (66.7%) of 15 cases.
In cases of ESWL, DMSA renal uptake decreased even 4-10 weeks (mean 7 weeks) after treatment. In conclusion, possivility of deterioration of renal function after ESWL was suggested.

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Side effects and serious complications of intravesical bacillus Calmette-Guérin (BCG) therapy were reviewed in 120 patients with transitional cell carcinoma of the urinary bladder from October, 1983 to June, 1989 at Hirosaki University Hospital. As local side effects, 102 patients (85.0%) had bladder irritability with frequency and/or micturition pain, and 46 patients (38.3%) had hematopyuria. As systemic side effects, fever in 43 patients (35.8%), elevation of serum GOT, GPT in 9 patients (7.5%), and malaise in 3 patients (2.5%) were seen. Serious complications were observed in 7 patients. 4 patients had a severely contracted bladder with decreased compliance less than 50ml, 2 patients had persistent arthritis and one patient had interstitial pneumonia. In all 4 patients with a contracted bladder partial cystectomy was performed before or after intravesical BCG therapy, and three of them received more than ten times instillation of BCG. It was suggested that contracted bladder most likely occurred after frequent BCG instillations in addition to decreased bladder compliance. Contracted bladder was irreversible in 2 patients. Histopathologically, there was marked fibrosis in the muscular layer of the bladder without tuberculous inflammatory changes. It might depend on the severity of fibrosis in the muscular layer whether contracted bladder was reversible or not. Persistent arthritis was nonspecific inflammation with negative culture results for mycobacteria in the joint fluid in 2 patients. In one patient with interstitial pneumonia, fiberoptic bronchoscopy with transbronchial lung biopsy demonstrated marked fibrosis of alveolar septums and increased lymphocyte count without tuberculous inflammatory changes. The pathogenesis of this complications is considered to be a hypersensitivity reaction to BCG.

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We attempted to clarify the anti-tumor activity and its mechanism of human recombinant tumor necrosis factor α (rTNFα). The established cell line KU-2, derived from human renal cell carcinoma, was treated with rTNFα alone or in combination with the following anti-cancer agents in vitro: actinomycin D (ACD), vinblastine sulfate (VLB), nimustine hydrochloride (ACNU), and methotrexate (MTX). In vitro studies, including cytotoxic assay, colony forming assay and flow cytometric DNA analysis were performed.
By cytotoxic assay, 21.4±4.0% and 34.8±4.7% of the cells were killed by 72 hour incubation with 100ng/ml of rTNFα alone, and 1ng/ml of ACD alone, respectively. An augmented cytotoxicity of 75.3±0.3% was observed by simultaneously adding 1ng/ml of rTNFα and 1ng/ml ACD. However, when KU-2 was treated with both 100ng/ml of rTNFα and 3μg/ml of ACNU or 2.5ng/ml of MTX, no significant increase in cytotoxicity was noted.
In the colony forming assay study, the colony forming efficiency (CE) of the control cultures was 31.8±8.1%. A 92.3±1.8% reduction in CE was demonstrated when 100ng/ml of rTNFα was added to the cultures. No augmented effects were seen between rTNFα and chemotherapeutic agents in this study.
In flow cytometric DNA analysis, no cell cycle specific effects of rTNFα were demonstrated, regardless of whether or not chemotherapeutic agents were added.
These results indicate that the cytotoxic and cytostatic activities of rTNFα may be mediated by separate mechanisms of action and that rTNFα affects more markedly KU-2 cells having clonogenic potentials. It is concluded that rTNFα has anti-tumor activities on renal cell carcinoma cells demonstrable by considerable colony forming assay studies.

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The anti-tumor activity of recombinant tumor necrosis factor α (rTNFα) against the renal cell carcinoma cell line KU-2 was studied in vivo, employing athymic nude mice. The nude mice were divided into six groups and each group was composed of six mice. Group I underwent no treatment, Groups II and III were injected with 5 and 10μg of rTNFα intraperitoneally, respectively. Group IV received 5μg of rTNFα intravenously and Groups V and VI were administered 2.5 and 5μg of rTNFα six times, given intravenously every other day, respectively. Evaluation of the study was performed according to Battelle Colombus Laboratories Protocol. Tumor regression was defined as RW<1; inhibition of tumor proliferation was defined as T_RW/CRW≤42%. Other results were defined as no effect. No obvious anti-tumor activity was observed in group II and III.
Though inhibition of tumor proliferation was noted in Group IV, death of two nude mice in this group was noted. When rTNFα was administered to the mice in Group V, complete disappearance of the heterotransplanted tumor in two nude mice and tumor regression in four were observed. No death of mice in this group occurred. When the dose of rTNFα was raised to 5μg (Group VI), however, five mice died.
The histopathological study revealed remarkable necrosis in the tumor tissue and congestion around the white pulps of the spleen 24 hours after intravenous administration of 5μg of rTNFα, although no obvious changes were noted in the liver, kidney and digestive organs.
After the same amount of rTNFα was injected in the peritoneal cavity, slight necrosis of the tumor was observed. Whole body autoradiography revealed moderate uptake of ¹²⁵I-labeled rTNFα in the tumor tissue eight hours after intravenous administration. However, only a slight uptake was recognized when it was administered intraperitoneally.
The radioactivity in blood 30 minutes to eight hours after intravenous administration of ¹²⁵I labeled rTNFα was statistically significantly higher than that after intraperitoneal administration (p<0.01) and the radioactivity in the tumor eight hours after administration was statistically significantly higher than 30 minutes after administration (i. v.: p<0.01; i. p.: p<0.05).
The radioactivity of ¹³¹I-human serum albumin in the tumor eight hours after the pre-treatment of rTNFα was observed to be higher with statistically significance than in the tumor without pretreatment of rTNFα.
Leucocytosis (p<0.01), erythrocytosis (p<0.05), elevation of hemoglobin (p<0.01) and hematocrit (p<0.05) were also observed two hours after intravenous administration of rTNFα. Systolic blood pressure of nude mice was 103.4±5.7mmHg before administration of rTNFα. Within 20 minutes after intravenous injection, systolic blood pressure dropped so low that it could not be measured.
The results showed that the route of administration of rTNFα was one of the important factors for the development of the anti-tumor activity of rTNFα and that multiple venous injection of a small amount showed stronger anti-tumor activities and weaker side effects than a single venous injection of a large amount of rTNFα.
Though the cause of hypotension still remains obscure our results suggests that hypovolemia plays a role in the development and persistence of hypotension. Our results further indicate that rTNFα may be a potent anti-cancer agent against advanced renal cell carcinoma.

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Fifteen patients with advanced testicular germ cell tumor were treated by VAB-6 chemotherapy after radical orchiectomy. CR was achieved in two (13.3%) and PR in nine (60.0%). The one, three and five year survival rates were 92.2, 64.2 and 51.4%, respectively. Nine patients (60.0%) remain with no evidence of disease (NED) after combined therapy (chemotherapy and surgery) with a median follow up of 4.3 months.
We performed resection of the residual tumors and examined histologically. Out of 11 cases, four (36.3%) were with necrosis/fibrosis, two (18.2%) teratoma and five (45.5%) cancer. All of the six cases with non-cancerous tissues remain in NED. However, only two of the five cases with cancerous tissues remain in NED.
We studied the NED rate based on four prognostic factors, (1) bulky abdominal diseases, (2) advanced lung diseases, (3) other metasteses, and (4)_choriocarcinoma. In our analysis, advanced lung diseases and choriocarcinoma were poor prognostic factors. We should treat these poor prognostic cases initially with VP-16, ifosfamide, high doses cisplatin etc, which were used as salvage drugs.

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Seventy-seven patients with advanced urothelial cancer were treated with methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC). Of these 77 patients, 65 could be evaluated for response and 74 for toxicity.
Response rates were 65% in the primary organs (62% in the renal pelvis and ureter, 67% in the bladder), 68% in the lymph nodes, 60% in the lung, 25% in the bone and 14% in the liver. Complete responses were noted in 11 patients (17%) and partial responses in 26 patients for an overall response rate of 57% (95% confidence limits 45 to 69%). The median durations of response were 11 months for complete response patients and 7 months for partial response patients. Of the 65 patients 20 (31%) are alive, and 1-, 2-, and 3-year survival rates were 65%, 37%, and 25%, respectively. While survival rates of responders were higher than those of nonresponders with a statistical significance until 15 months, no significant differences were observed in survival rates between these two groups in the subsequent period.
The M-VAC regimen was used for 15 patients as a neoadjuvant chemotherapy. Of the 15 patients, 8 responded and primary organs were preserved in 6 of the 8 responders. Histological effects classified according to Oboshi-Shimosato's criteria were G. I in 9, G. IIA in 3, G. IIB in 1, and G. IVC in 2. There were no significant differences in survival rates according to responses and histological effects.
Factors related to response were analyzed with a multiple logistic regression model on 54 patients treated with intravenous administration of drugs and whose histological type was transitional cell carcinoma. The analysis results indicate that the presence of distant metastases is an important factor in predicting poor efficacy.
Sixteen of 74 patients (22%) had white blood cell count of less than 1, 000 cells per mm³ in the first cycle, while the decrease of platelet count was mild in degree compared with that of the white blood cell count. Patients with elevations of serum creatinine, GOT, and GPT were low in frequency, and toxic symptoms were controllable. Factors significantly related to the occurrence of side effects were sex, performance status, prior radiotherapy, prior chemotherapy, and the method of drug administration. Among these factors, prior radiotherapy was related to severe decrease of white blood cell count.
While an excellent overall response rate was provided with the M-VAC regimen, disadvantages of the present regimen were low effectiveness in the bone and liver, and short duration of response. M-VAC chemotherapy also did not prove to have a long-term benefit on survival.

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We have investigated the structure of canine middle ureteral smooth muscle anatomically. In a transverse section inner fibers appeared to be longitudinal and outer fibers appeared to be circular. In the parallel sections with the wall of longitudinal ureteral muscle, inner and outer fibers appeared to be oblique in a mesh structure. In parallel sections with the wall of helical ureteral muscle, fibers appeared to be longitudinal. Anatomical analysis showed that canine ureteral smooth muscle is entirely composed of spinal fibers in a mesh structure and that the helical muscle strip have continuous fibers though the inner fibers have a tendency to run longitudinally and the outer fibers circularly.

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I have investigated the effects of autonomic drugs and prostaglandins on in vitro smooth muscle spontaneous contractions and made the quantitative analysis of autonomic receptors in the canine ureter. Ureteral muscle strip cut helically usually generated spontaneous contractions whereas those cut circularly or longitudinally did not generate spontaneous contractions. These results suggest the importance of knowing which direction to cut the ureteral smooth muscle in order to generate spontaneous contractions. Norepinephrine (α), phenylephrine (α1), carbachol (muscarinic) and PGF2αcaused significant increase in contractile force. Terbutaline (β2) and PGE2 caused significant decreases in contractile force, while dobutamine (β1)and clonidine (α) caused no effect. Autonomic receptor densities were determined using radiology and binding techniques. The number of maximum biding sites (Bmax) of ³H-prazosin (PZ), ³H-yohimbine (YOH), ³H-dihydroaloprenolol (DHA)and ³H-quinuclidinylbenzilate (QNB) were 53.8, 16.9, 11.2 and 5.28fmol/ml protein, respectively. These data suggest that the contractile responses to adrenergic and cholinergic agonists in the canine ureter are mediated through functional adrenergic (α1, β2) and muscarinic cholinergic receptors and that the prostaglandins have a role in the contraction of the canine ureter.

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The most important information for treatment of bladder cancer is to known its exact staging. A whole layer needle biopsy technique has been developed for this purpose. Recently, neoadjuvant therapy has been used for invasive bladder cancer. Although down staging of bladder cancer after neaodjuvant therapy are evaluated by CT or ultrasound, these imaging are not reliable. We examined 11 invasive bladder cancer patients by whole layer needle biopsy pre and post neoadjuvant therapy. All cases were pT3-4 by pretreatment biopsy. After neoadjuvant therapy 4 were changed to pT0 by needle biopsy. another cases were no change or minimal change. In 4 changed to pT0, 3 were done total or partial cyctectomy and the results of pathological diagnosis of cystectomized specimens were also pT0. Another one case changed to pT0 is selected as candidate for bladder sparing and the patient is now in close surveilance. All 4 cases changed to pT0 were done combined treatment by chemo (internal iliac artery infusion) and radiotherapy. In remaining 7 cases, pathological staging of surgical or autopsy specimen agreed with that of whole layer needle biopsy.
Whole layer needle biopsy showed no severe comlication, except minor bleeding from the bladder wall. Tumor seeding into the needle tract was no observed up to present time.
In conclusion, this biopsy system is useful for evaluation of the change of stage with chemotherapy and/or radiation therapy. By using this technique we can select the cases for candidate of bladder sparing.

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From June 1984 to March 1988, patients with newly diagnosed stage D2 prostate cancer were treated with protocol 1. This comprised oral hormonal agents either diethylstilbestrol diphosphate (Honvan: 300mg/day) or estramustine phosphate (Estracyt: 560mg/day), or chlormadinone acetate (Prostal: 100mg/day), plus intravenous cyclophosphamide (CPM, 0.5-1g/m²) every 3-4 weeks. From May 1988, protocol 2 was used in a randomized study of castration alone versus castration plus intravenous methotrexate (MTX, 20mg/m²) every 2 weeks. Forty-nine of 53 patients who underwent the two protocols were evaluable for the response. The response rates according to the NPCP criteria were 92% (11/12) for Honvan, 100% (9/9) for Estracyt, 78% (7/9) for Prostal and castration plus MTX, and 80% (8/10) for castration alone. There were no significant differences among these treatments. The median response duration and survival time (months) were 16 and 44, respectively, for Honvan, 19 and 37 for Estracyt, 12 and 43 for Prostal, 11 and 15 for castration plus MTX, and 13 and 13 for castration alone. The short survival times of the castration alone and castration plus MTX groups were due to a short follow-up period. There were no statistical differences among the oral hormonal agent plus CPM groups. However, the 2-year survival rate (Kaplan-Meier method) was higher in the CPM and MTX groups than in the castration alone group. Survival was longer in the good performance status (P. S.) group than the poor P. S. group (p<0.05 by Wilcoxon test) and in the responders than the non-responders (p<0.01). Side effects were not excessive in the chemotherapy groups and patient compliance was good.

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The responses of the urethra to hypogastric nerve (HGN) and lumbosacral sympathetic chain (SC) stimulation were observed in 25 chloralose-anesthetized cats. Urethral perfusion pressure was monitored as an index of functional urethral responses. SC was stimulated at four points from L4 to S1. Urethral constrictive response induced by HGN stimulation (ΔP: HGN) was significantly larger in male cats than in female cats. But there was no difference between male and female cats in urethral constrictive response induced by SC stimulation (ΔP: SC). ΔP: HGN was significantly larger than ΔP: SC in both sexes, and the ratio of ΔP: HGN to ΔP: SC (L7-S1) was 2.7 to 1 in male cats and 1.7 to 1 in female cats. ΔP: HGN was blocked by the alpha-adrenergic antagonist phentolamine (1-2mg/kg) and reduced about 50% by autonomic ganglion blockade with hexamethonium bromide (2mg/min, 25-50mg). ΔP: SC was blocked by both phenotolamine and hexamethonium bromide. In order to examine the pathways of projections of sympathetic fibers from the sacral SC to the urethra, HGN, pelvic nerve and pudendal nerve were transected serially. ΔP: SC (L7-S1) was decreased 0%, 12% and 50% by transection of HGN, pelvic nerve and pudendal nerve, respectively. After severance of these three nerves, ΔP: SC (L7-S1) was reduced 62%, but not abolished. These data suggest: 1) The effect of HGN to the feline urethra is more prominent than that of SC in both sexes and significantly larger response was noted in male cats with HGN stimulation but not with SC. 2) Urethral constrictive responses induced by HGN and SC stimulation are mediated through alpha-receptors. 3) Short adrenergic neurons contribute to 50% of the urethral constrictive response induced by HGN stimulation. and 4) Some of the sympathetic fibers descending in the sacral SC reach the urethra not through HGN, pelvic nerve or pudendal nerve, but through an independent direct pathway.

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A 38-year-old male patient with the past history of polioencephalopathy was admitted with urinary retention and high grade fever. Although he was able to walk he had the intelligence of a 3-year-old child and his spine, thorax, fingers were deformed remarkably. Immediately after the admission, cystostomy was carried out and 600ml of stinky and cloudy urine was noted. Although intensive antibiotic therapy was performed, high grade fever with leucocytosis (>15000/mm²) persisted for more than 10 days. Retrograde urethrogram showed stricture in the anterior urethra as well as irregular filling defect in the bulbomembranous urethra. After urethral dilation using urethral dilators, 18Fr nephrostomy balloon catheter was indwelled and the patient was discharged.
However, the urethral irregular filling defect was unchanged and cytological examination of urine and urethral secretions revealed class V. After the readmission, endoscopic examination revealed papillary tumor lesions occupying the whole posterior urethra were found. With the diagnosis of invasive posterior urethral cancer, anterior exenteration by en bloc pubectomy, pelvic lymphadenectomy and ileal conduit urinary diversion were carried out.
On the surgical specimen, the tumor occupied the bulbomembranous and prostatic urethra. Histopathological diagnosis was TCC G3>SCC, stage B. Since the tumor invaded the serosa of the membranous urethra, we thought it could not be removed completely without the pubctomy.

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A case of Wilms' tumor in a 57-year-old woman is reported. She was with a complaint of a palpable mass on the right upper abdomen. CT scan showed a non-hemogenous mass arising from the lower pole of the right kidney. After transarterial embolization, right transabdominal radical nephrectomy was performed under the diagnosis of renal cancer. Histopathological study revealed Wilms' tumor stage 2. Over the two years after surgery the patient is disease-free.
Wilms' tumor is rare in adults. The prognosis of adult Wilms' tumor is recognized to be poorer than that of children. Recently, Wilms' tumors in children are classified into two histopathological groups, that is “favorable histology” and “unfavorable histology” according to the cell differenciation. Based on a collection of the previous Japanese and English reports, we analyzed the relationship between the histopathological features and the prognosis in adult Wilms' tumor. Ten cases of unfavorable histology have very poor prognosis, with the two year survival rate of 22%. In contrast, that of 24 cases of favorable histology was 71%. In particular, all cases of the epithelial predominant type presenting favorable histology, including stag 4 cases, survived over two years. Our case was the epithelial predominent type presenting favorable histology. That is probably one of the chief reasons of the good prognosis.
In conclusion, the above-mentioned results show that in adult Wilms' tumor, the prognosis of unfavorable histology is very poor, but that of a low stage or the epithelial type presenting favorable histology is, as in children, relatively good.

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