Modalities for the diagnostic imaging of the prostate are surveyed. Transrectal sonography is thought to be the best method for the purpose, because of its non-invasive nature, fine picture quality, sufficient reproductivity and less expensive cost. Up-to-date utilizations of the method are described, such as diagnostic capability, staging, monitoring, screening and intervention. CT is less effective but MRI is promising to visualize internal structure inside the prostate. Two very new techniques, namely, ultrasonic Doppler color flow mapping and positron emission CT (PET), of which application to the prostate is being investigated originally in our laboratory, are introduced.

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Polymorphonuclear leukocytes (PMNs) play an important role in host defense system. Upon interaction with soluble or particulate matter, PMNs generate active oxygen species (AO), which act on killing of bacteria. In urinary tract infection, urinary PMNs are assumed to have bactericidal activity in urine. Basal experiments were studied on the AO generation of urinary PMNs, monitored by mainly the luminol-dependent chemiluminescence. It was indicated that urinary PMNs, isolated from patients with urinary tract infection, generated AO in physiological medium. This activity of urinary PMNs was found to be significantly inhibited rather than that of PMNs in blood, and this suppression was suggested to be time-dependent. PMNs were affected significantly by osmolarity of reaction medium. These changes were associated with intracellular free calcium. PMNs exposed in hyposmotic medium generated AO, just as they were stimulated. However PMNs exposed in hyperosmotic medium did not generate AO. The stimulation-dependent AO generation of PMNs was increased in hyposmotic solution, while in PMNs incubated at 37°C for 60min in hyposmotic solution, this generation was decreased than controls. On the other hand, the stimulation-dependent generation was decreased in hyperosmotic solution, while incubated in hyperosmotic solution, this generation was increased. These results suggest that ability of urinary PMNs is regulated by urine osmolarity and retaining time or many other factors, however urinary PMNs are primed and maintain bactericidal activity.

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The BCG 65kDa protein is part of the 60kDa heat-shock protein (hsp) family. It is clear that hsp has a huge homology among mammalian and bacterial cells. In our study, we have observed the relevance of this protein in the anti-tumor response.
Antibody production against the BCG 65kDa protein was determined by solid phase ELISA using the sera of 51 bladder cancer patients who have undergone BCG instillation therapy. The BCG 65kDa protein was made by E. coli transfected with pTB12 (plasmid DNA) which encodes this protein. It was clearly observed that the level of serum antibody titer to this protein was raised by the above instillation therapy.
In order to investigate the role of this protein in anti-tumor response, we developed monoclonal antibodies against BCG 65kDa protein. Four monoclonal antibodies were developed (B-20, B-97, B-108, B-167). We also estimated the epitope defined by each monoclonal antibody by using the truncated protein which was produced by E. coli transfected with the deletion mutants of pTB12.
At this stage, we proceeded with observation of the cross epitope between mammalian cancer cells and BCG after using these monoclonal antibodies. There is no cross epitope defined by B-20, B-97 and B-167 in mammalian cells. However, the epitope defined by B-108 exists in normal tissue as well as in bladder cancer cells.

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The effects of urinary pH and acid-base balance on the calcium oxalate stone formation was investigated by two experiments.
24-hr urine samples were collected from 15 recurrent CaOx stone formers, 9 single stone formers and 6 age-matched controls. Inhibitory effect of 1% urine in various pH (4.0-9.0) were calculated by a seed crystal method. In the seed crystal system, there were no significant differences in the inhibitory activity of aggregation (Ia) and in the inhibitory activity of size (Is) for each pH of metastable solution between the stone former group and the control group. However, the value of Ia and Is showed a tendency of rise in proportion to a rise in pH.
Rats model for calcium oxalate urolithiasis were fed with three different diets (1% NH₄Cl, 5% NaHCO₃ and 8% NaHCO₃ diet) for three weeks. On the fourth week, 24-hr urine samples were collected. In the animal experiment, calcium oxalate stone formations were predominantly recognized in the kidney of the 1% NH₄Cl diet group. The biochemical data showed an increase of urinary calcium and oxalate, and a decrease of urinary citrate.
These results suggest that low urinary pH and metabolic acidosis are promoters of the calcium oxalate stone formation.

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From 1972 to 1989, 21 patients underwent bladder replacement with sigmoid colon after cystectomy for bladder cancer. A portion of sigmoid colon (about 15 to 20cm) was isolated and anastomosed to the urethral stump. Then the ureters were implanted in the sigmoid colon via submucosal tunnels.
There were 20 men and 1 woman, ranging in age from 24 to 71 years (average 51 years). Preoperative investigations showed that all the cases were free of metastasis. Five years survival rate was 60.7% and there was no operative mortality. There was urethral recurrence in one case and in that case postoperative histopathology revealed carcinoma in situ with tumor.
All patients were able to void by themselves without any difficulty. Five patients complained mild incontinence at daytime and all patients had mild incontinence during deep sleep at night, but all of them could maintain their normal daily life like before.
The major postoperative complications were: leak at the site of anastomosis (between sigmoid colon and urethra) in 6 cases, hydronephrosis in 2 cases, VUR in 2 cases and bladder stone in 1 case. The patients who underwent bladder replacement with sigmoid colon were well satisfied, because there were no external stoma and the patients could void by themselves.
From now, we want to improve our operative method in order to avoid postoperative incontinence.

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Ninety-two of a total 107 renal cell carcinomas excluding papillary, sarcomatoid and other uncommon histological types were classified into 3 groups based on architectural variations. Statistically analyses were carried out for prognostic significance.
Histological criteria of 3 groups were defined as follows. Group I consists predominantly of tubular formations with characteristic cystic change. Group III shows solid proliferation without tubular formations, and Group II shows small alveolar or trabecular structures with inconspicuous tubular formations. According to the survival curves (Kaplan-Meier method), the prognosis of Group I was significantly better than II and III. Ten year survival rate of each group was 88±7.8% in Group I, 39±8.8% in Group II, and 0% in Group III. The distribution of T and V stages in the 3 groups were not significantly different. Nuclear grading of Group I and II was not so different, though high grade cases predominated in Group III. Therefore, the present grading of alveolar type renal cell carcinoma based on architectural atypia was considered to be a useful prognostic parameter.

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Bladder dysfunction is a common complication of diabetes mellitus and is attributed in part to peripheral neuropathy. Voiding function is mainly controlled by muscarinic receptor function. Therefore, I investigated first the biochemical and functional characteristics of urinary bladder muscarinic receptors and then the effects of experimental diabetes on them. Experimental diabetes was induced in 2 month-old male rats by intravenous injection of 65mg/kg of streptozotocin (STZ). Effects of diabetes mellitus were investigated 2, 4 and 8 weeks after injection of STZ. The amount of muscarinic receptors labelled with ³H-quinuclidinyl benzylate (QNB) was higher in the bladder dome of diabetic animals than control animals, while the affinity for its binding sites was similar in both groups. Muscarinic agonists and antagonists inhibited ³H-QNB binding with similar inhibitory constants (Ki) in control and diabetic domes. The rank order of inhibition of ³H-QNB binding by muscarinic agonists and antagonists: bethanechol>pirenzepine>carbamylcholine>acetylcholine>atropine, is consistent with the absence of M1 receptors in the bladder dome. In functional studies muscarinic agonists induced a larger contractile response in bladder dome muscle strips from 8 week-old diabetic animal than those from controls. The rank order of ED₅₀s were similar in the control and treated groups, being in good agreement with the Ki values obtained from receptor binding studies. These data show a direct correlation between the diabetes-induced biochemical and functinal alterations in muscarinic receptor properties of the rat bladder.

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I investigated the biochemical (Bmax, K_D) and functional (contractile force) characteristics of autonomic receptors in the 1-day-old rabbit urinary tract smooth muscle, and compared the data obtained to those already reported in adult rabbits. The rank order of the receptor densities in neonatal rabbits are dome>base>urethra>ureter for α₁ (³H-PZ), ureter>urethra>base>dome for α₂ (³H-YOH), dome>base>urethra>ureter for β(³H-DHA) and dome>base>urethra>ureter for muscarinic (³H-QNB). Unlike the findings in the adult rabbit, there is a much larger number of functional muscarinic receptors in the bladder dome and a much smaller number of functional α₁-receptors in the urethra of neonatal rabbits. The differences observed in the pattern of distribution of these receptors between neonatal and adult urinary tracts may play a determinant role in the physiological development of the urinary system.

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The correlation between the resected weight of prostate and the estimated weight of prostate by transrectal longitudinal ultrasound was evaluated for 53 patients with benign prostatic hypertrophy. Sonography was done with a real time linear scanner and 5.0MHz transducer. Maximal prostatic dimensions were measured along the two major axes, namely the maximal length and the maximal thickness of total prostate and adenoma. By regarding benign prostatic hypertrophy as an ellipsoid, we calculated the weight of prostate according to the ellipsoid formula. The correlation coefficient was calculated as; r=0.929, Y=0.942X_t-2.642 (X_t: total estimated weight), r=0.962, Y=0.965X_a+0.028 (X_a: estimated weight of adenoma). The estimated weight of the prostate correlated with the resected weight of the prostate.
These results suggested that rough estimation of the weight of benign prostatic hypertrophy was found to be possible by using this calculation technique.

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We performed 308 series renal biopsies during 4 years (1985-1989) and 289 cases were examined by light microscopic, electron microscopic, or immunofluorescent study. Clinically, chronic nephritic syndrome was most frequent (55.4%), followed by nephrotic syndrome (15.1%), and recurrent or persistent hematuria (12.8%). Pathologically, IgA nephropathy was most popular (39.3%), followed by normal glomerulus (9.1%), and thin basement membrane disease (8.7%). Glomerulonephritis clinically recognized with recurrent or persistent hematuria, hardly showing proteinuria, in 81.6% of the cases, consisted of normal glomerulus, or thin basement membrane disease by electron microscopic and immunofluorescent examinations. The remainder (18.4%) was with IgA nephropathy, which was histologically mild. On the other hand, cases of chronic nephritic syndrome (latent type) with persistent proteinuria and hematuria were with glomerulonephritis of various types including IgA nephropathy in 78.8% of the total cases. Therefore, proteinuria is an important sign of glomerulonephritis.
In investigation in different age groups, IgA nephropathy was seen in about 40% of both pediatric and adult cases, whereas minor glomerular abnormalities and thin basement membrane disease were more frequent in pediatric cases. Tubulo-interstitial lesions and glomerular lesions in vascular or metabolic diseases were recognized more in adults than in children. Membranous, glomerulonephritis (17 cases including 4 pediatric cases), complicated with malignant tumors such as bladder or rectal cancers and hepatoma was found in 3 aged patients. Examination for malignant tumor would be necessary for aged patients with membranous glomerulonephritis.
As for the prognosis of IgA nephropathy, because histological changes of IgA nephropathy varied widely from very mild state to severe state, the prognosis is not always good. Histological changes tended to be the more severe, the more intense was proteinuria.
As for the complications of renal biopsy, macroscopic hematuria was recognized in about 5% of the cases, but there were no severe complications.

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Using the antibody for glutathione S-transferase (GST) purified from human kidney, normal testes and experimental cryptorchid testes from newborn to 20-week-old rats were immunohistochemically stained by the peroxidase antiperoxidase (PAP) method. The cryptorchidism was surgically created at 1 week of age. The localization of GST was particularly examined by light microscopy, and the amount of Leydig cells was measured by a stereological method.
1. Leydig cells in the normal and cryptorchid testes showed strong GST activity at all ages. The amount of these cells in normal testes increased from 4 to 8 weeks of age and then slightly decreased, whereas in cryptorchid testes it was significantly larger than in the normal testes at 20 weeks of age, indicating hyperplasia of Leydig cells.
2. In the normal and cryptorchid testes, degenerating primary spermatocytes with GST activity appeared in the seminiferous tubules at 2 to 4 weeks of age. In the cryptorchid testis, degenerating germ cells with GST activity were also found in the regressing seminiferous tubules after 4 weeks of age. It is possible that GST acts as a detoxification system in the degenerating germ cells.
3. The PAP staining of GST in the rat testes is considered to be useful method for evaluating metabolic function of the spermatogenic cells and the distribution and amount of Leydig cells.
4. Experimental cryptorchidism showed that germ cells become sensitive after 4 weeks of age.

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Of 173 patients with renal cell carcinoma treated at the Keio University Hospital between 1979 and 1989, 48 cases were found to have their tumors incidentally (group 1), and the remaining patients presented with signs and/or symptoms related to their tumors (group 2). In this study we attemped to define the clinicopathological and ploidy characteristics of the tumors in the patients of the two groups.
The number of patients having tumor stages not exceeding pT2NOMOV- was significantly higher in group 1 (81.3%) than in group 2 (36.0%) (p<0.001), and the median tumor size was significantly smaller in group 1 (4.32±2.38cm) than in group 2 (7.86±4.07cm) (p<0.001). The survival rate in group 1 was significantly favorable when compared with group 2 (p<0.005). And even in the same stage (pT1-2NOMOV-) there were statistical significance in the survival and relapse rate between the two groups (p<0.05), which indicate that renal cell carcinomas detected incidentally are associated with biologically low malignant potential.
From 1985, flow cytometric DNA analysis was performed in 32 tumors from the group 1 and in 50 from the group 2. The frequency of occurence of aneuploid pattern was significantly lower in tumors from the group 1 (25.0% in the overall patients and 16.0% in those with stage pT1-2NOMOV- tumors of group 1) than in those from the group 2(52.0% in the overall patients and 42.9% in those with stage pT1-2NOMOV- tumors) (p<0.05). These results also suggest that renal cell carcinomas detected incidentally are associated with low malignant potential biologically.

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The sequential changes in maximum active stress, contractile proteins and collagen contents in the dilated ureter were determined in the rabbit ureters, which was partially obstructed for the intervals of 2 to 48 weeks.
Maximum active stress and myosin content showed similar changes with the obstruction interval. i. e., both decreased first and then increased from week 2, and reached maximum at week 8, and after that, gradually decreased. Actin content did not show any significant changes. Collagen content showed almost the same changes as myosin content and maximum active stress by week 2. Then the collagen content inceased rapidly from week 6 to week 10, and continued to increase gradually until 48 weeks after obstruction.
A significant correlation was demonstrated between maximum active stress and myosin content while no significant correlation was found between maximum active stress and actin content. The maximum active stress decreased as the collagen content increased after week 8. Thus, there was a significant, negative correlation between them.
Finally, the ratio of myosin content to collagen content (myosin/collagen) was related to maximum active stress. This ratio was more closely correlated with maximum active stress, indicating that myosin-collagen ratio is a good means of predicting contractility of the obstructed ureter.

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Thirty patients (16 men and 14 women) with cystine urinary stones were treated by extracorporeal shock wave lithotripsy (Dormer HM-3) from December 1984 through October 1989. The average patient age was 35.2 years with a range of 14 to 59 years. Seventy per cent of these subjects had had previous open surgical operations for stones. The cases consisted of 7 ureteral stones and 37 renal stones, including 15 staghorn calculi. An average of 1.3 session of ESWL was carried out to treat ureteral stones. Thirty-seven renal units with renal stone required 96 sessions of lithotripsy (average 2.6 sessions per unit). Seven patients with ureteral stones required auxiliary procedures, i. e., one transurethral lithotripsy (TUL), two percutaneous nephrostomies (PNS) and one open surgery. Thirty-seven renal stones, including staghorn calculi was treated by ESWL and auxiliary treatment of 21 TUL procedures, one PNS, 16 PNL procedures and one chemical chemolysis.
Successful fragmentation (residual debriss≤4mm) was achieved in 85.7% of ureteral stones, 90.9% of renal stones and 73.3% of staghorn calculi. The stone free rates of patients with ureteral stones, renal stones and staghorn calculi were 71.4%, 50.0% and 53.5%, respectively, at 3 months after ESWL.
No serious complications were seen in this series. Fever above 38.5°C was the most common complications (13.5%). Ureteral perforation was encountered once in TUL procedures. Transfusion and selective arterial embolization were needed for one case treated by PNL procedures.
Although cystine stone is harder to be fragmented by ESWL than other stone composition, ESWL and endourology may be effective and safe procedures for cystine stone patients. ESWL monotherapy usually achieves good results for small renal stones and ureter stones. For larger renal stones including staghorn calculi endourology, especially PNL, is the preferred modality of treatment.

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The nuclear area, N/C ratio and anisonucleosis by morphometry and the DNA content by image photocytometry of paraffin-embedded tissues of 9 cases of prostatic hypertrophy and 48 cases of carcinoma obtained by open surgery, needle biopsy or by autopsy were correlated with histological grading. In histological grading, in addition to 9 benign hypertrophy cases, 11 were classified as well differetiated adenocarcinoma, 19 as poorly differentiated adenocarcinoma and 1 as small cell carcinoma.
All 14 tumors taken from distant metastasis were classified as poorly differentiated adenocarcinoma.
Correlation of the data by tumor cell morphometry with those of nuclear image photocytometry was carried out on surgical materials alone. In autopsy materials, DNA ploidy patterns were compared between primary lesions and metastases.
The DNA histogram patterns of most cases were classified into 4 groups. Hypertrophy was differentiated from carcinoma by the histogram patterns. There were significant correlations between mean DNA value and morphometric factors. One of the 4 histogram patterns had a higher mortality than others. The DNA histograms did not distinguish between the primary and metastatic lesions of the same patients. However, the DNA histograms constructed from metastasis frequently showed a single stem-line of the primary lesion. This study disclosed several correlations between histological grading and morphometrical factors.

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In order to determine the localization of α₁-adrenoceptors in human hypertrophied prostates, in vitro autoradiography was performed on the frozen specimens from 13 enucleated hypertrophied prostates with [¹²⁵I]-HEAT (iodo-2-[β-(4-hydroxyphenyl)-ethylaminomethyl] tetralone) and [³H]-prazosin. In vitro autoradiograms showed macroscopically the specific binding site on the areas seemed to the nodular area for [¹²⁵I]-HEAT, but not so clear specific binding sites for [³H]-prazosin. Microscopic autoradiograms seemed to show binding sites located mainly on the interstitium beneath the gland, and partly on the basement membrane and epithelium of the prostatic gland. Further studies are needed to show clearer specific binding sites of α₁-adrenoceptors.

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A study was made on treatment-related factors, notably prognosis, in 148 patients treated by surgical resection of the primary lesion among 170 consecutive patients who were admitted to the Department of Urology, Gunma University for the treatment of renal cell carcinoma during the period from September 1961 through August 1989.
Operative procedures used in this series were radical nephrectomy in 100 patients, simple nephrectomy in 46, partial nephrectomy in 1 and tumor enucleation in 1, lymph node dissection being performed in 53 of the 100 patients treated by radical nephrectomy.
The patients receiving surgical resection of the primary lesion were stratified according to sex, PS, disease stage, surgical procedure, lymph node dissection and weight of renal substance resected and comparisons were made on survival rate and recurrence rate among patients in different strata in an effort to observe if these factors are determinant of postoperative prognosis.
No significant difference in survival rate was observed between sexes. Patients displaying a PS value of 0 had a significantly higher survival rate than those having a PS value of 1 or above. Whereas a significant difference in survival rare was noted between stage III_A+III_B+C disease patients, no significant difference was observed among stage I, II and III patients, thus stages up to III_A being considered low stage.
Radical nephrectomy was associated with a significantly higher survival rate than simple nephrectomy in low stage (stage I-II) disease patients. However, there was no significant difference in survival rate between stage I-II disease patients with vs. without lymph node dissection.
A significantly higher survival rate was obtained in patients having less than 500g of renal substance removed than those having 500g or more of renal substance removed. No significant difference was noted between the two groups of patients so far as those with stage I-III_A disease were concerned, however.
When the recurrence of malignancy was studied in relation to operative procedure and disease stage, it became obvious that the recurrence rate was lower in patients with stage I or II disease treated by radical nephrectomy than in those who underwent simple nephrectomy. Among patients treated by radical nephrectomy, those with stage II disease had recurrence rate (about 30%) which was almost equal to that for those with stage III_A disease.
Among stage III or more advanced disease patients, the extrapleural lumbar approach was employed for noncurative resection in all patients undergoing simple nephrectomy, while the transabdominal or thoracicoabdominal approach was used in patients treated by radical nephrectomy, allowing for an extensive operation involving retroperitoneal lymph node dissection, vena caval tumor thrombectomy or conjoined resection of contiguous organs.
Particularly in stage III_A patients, since they had a survival rate not significantly different from that for stage I and II patients and a recurrence rate comparable to stage II patients, it was considered of utmost importance to perform a perfect tumor thrombectomy.
These results led us to conclude that a PS value of 0 is a primary prerequisite for a favorable outcome of surgery for renal cell carcinoma; that a radical nephrectomy is the treatment of choice for stage I-II disease, and that, for stage III or more advanced disease, an extended operation including radical nephrectomy by the thoracicoabdominal approach is highly recommendable, because it will certainly provide an improvement of prognosis.

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Twenty-eight patients with a tumor thrombus 914 in the inferior vena cava and 14 in the renal vein), among a series of 170 renal cell carcinoma patients receiving hospital treatment at the Gunma University during the period from 1961 to 1989, were explored for clinical features, with the results leading to the following conclusions:
1) There were 19 male and 9 female with respective mean ages of 62.1 and 54.4 years.
2) The disease was right-sided in 16 patients and left-sided in the other 12, but there were no striking left-to-right difference in tumor location.
3) The most frequent chief complaint was symptoms arising from the urinary tract. Among symptoms and sings occulusion of the inferior vena cava or renal vein, proteinuria was most frequent, being present in 56% of patients with clinical evidence of occlusion, followed by tortuosity of veins of the abdominal wall and edema in the lower extremities noted in 3 patients.
4) Selective renal arteriography demonstrated tumor hypervascularity in all 22 patients (except for one with a hypovascular tumor mass) and A-V shunt at a high percentage. Profuse striated vascular pattern representing arterialization of an extensive tumor thrombus was also noted, particularly with intracaval involvement. Venacavography demonstrated neoplastic thrombi in the inferior vena cava as filling defects, thus proving the diannosis. CT also provided diagnostic evidence of a tumor thrombus in all cases except for one in which it failed to detect a tumor thrombus in the renal vein preoperatively, with an accurate diagnosis rate of 100% for intracaval tumor thrombi and 83% for tumor thrombi in the renal vein.
5) The extent of tumor thrombosis was graded in the entire 28 patients as well as in 22 patients operated upon and correlated with prognosis. The results indicate that the extent of tumor thrombosis had no bearing upon the pathologic stage of disease. Stage III_c or more advanced cases had a poor prognosis irrespective of the extent of tumor thrombosis; 6 patients not undergoing operation all died of cancer within 12 months of onset, while patients operated upon all had a fatal outcome within 20 months excepting for one with stage IV_B disease and extention of intracardiac type who has been surviving for 11 months. Stage III_A disease patients had a survival time of 10 to 98 months even in the presence of recurrence, thus generally having favorable prognosis regardless of the degree of extention of a tumor thrombus.
6) With the exception of 1 patient treated by transabdominal simple nephrectomy and 3 by translumbar simple nephrectomy, all patients underwent a transabdominal or thoracoabdominal radical nephrectomy, either of these approaches being neccessary for successful performance of an intravenous thombectomy.
7) The operative procedure of choice may vary depending upon the extent of tumor thrombosis. We consider, therefore, that a key for successful operation is to accurately determine the extent of a tumor thrombus by preoperative diagnosistic imaging.

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A 75-year-old male patient showed an extensive erosion mainly restricted to the penile site, which was found when he received appendectomy. The penile lesion had persisted for about ten years, during which period the erosion extended gradually while he missed to consult a physician. The lesion was a florid and wetting erosion, with a definite boundary, which covered the entire circumference of the penile foreskin and also extended to the suprapubic area, scrotum and external urethral orifice. Although the diagnosis could not be made by biopsy, extra mammary Paget's disease was strongly suspected. Bilateral modified inguinal lymphadenectomy and systemic evaluation were first performed to confirm that there was no metastasis or complexed disease in other organs. Then extensive wide resection of the skin lesion and reconstruction using a split-thickness skin graft were performed. Histopathological examination of the surgical specimen revealed poorly differentiated squamous cell carcinoma, although most part showed only inflammatory erosion.
Clinical course and the histopathological findings including specific staining patterns led to the diagnosis of poorly differentiated squamous cell carcinoma originated from erythroplasia. During post-operative 18 months until now, no local recurrence or distant metastasis has been observed.

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