Stage classification of cancer is a method for objectively describing the status of a tumor. For more than 30 years, the TNM classification system was applied on various kind of malignant neoplasms, whose basic principles were: 1) applicability to all anatomic sites; 2) independence from treatment, and 3) susceptibility to further modification on the basis of information supplied by surgery and histopathological description.
Thus far, TNM classification system has made a great contribution to 1) aid the clinician in the planning of treatment; 2) give some indication of prognosis; 3) assist in evaluation of the results of treatment; 4) facilitate the exchange of information between treatment centeres; 5) contribute to the continuing investigation of human cancer.
However, the publication of the fourth edition of the TNM classification has caused great consternation to urologists because of lack of logic for its complete revision.
In this review analyses were done on the changes in the TNM classification of the genitourinary tumors described in the 3rd, 4th and 4th revision.
Discussion was also made in relation to the TNM systems and classification systems in the general rules for clinical and pathological studies on urological malignancy of Japanese Urological Association.

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DNA ploidy was investigated using flow cytometry on fresh surgical specimens from 116 cases with renal cell carcinoma. DNA diploid tumor was observed in 39 cases (33.6%) and aneuploid in 77 cases (66.4%). DNA aneuploid group was further classified into 3 subgroups by DNA index (D. I.); near-diploid group (D. I.: 0.8-1.2, 21.6%), near-tetraploid group (D. I.: 1.8-2.2, 12.9%) and other aneuploid group (31.9%). DNA ploidy pattern correlated with clinical stages and histological grading, indicating significantly a higher incidence of DNA diploid in cases in stage I and grade 1. DNA clonal heterogeneity was observed in 48.1%, and homogeneously diploid was in 28.6% of 77 cases who were analyzed more than 2 specimens. Incidences of DNA heterogeneity and homogeneous diploid correlated with the number of analyzed specimens and our results showed that more than 4 specimens were necessary to diagnose the DNA ploidy patterns. The near-tetraploid group was shown to have an extremely poor prognosis compared with the diploid group and the other aneuploid group. There were no significant difference between the diploid group and the aneuploid group in terms of the early prognosis, however, the incidence of disease recurrence was significantly higher in the aneuploid group. Our results demonstrated that DNA ploidy was an useful prognoctic factor in the evaluation of patients with renal cell carcinoma.

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One approach to the treatment of obstructive azoospermic cases in whome either vasovasostomy cannot be performed or the vas deferens is absent is to construct an artificial spermatocele in the epididymas. By using this method to recover sperms for use in AIH, we have succeeded in achieving pregnancy in only 2 of 35 cases, leading us to investigate the fertility of the recovered sperms. Sperm fertility was investigated by the hypoosmotic swelling (HOS) test, observation by confocal laser-scanning microscope (CLSM), flow cytometry and hamster egg sperm penetration test. The percentage of swollen sperm determined by the HOS test was 15.0-83.3%, with a mean of 47.6±16.1%, significantly lower than the values of the normal group and the infertile male group, excluding cases of obstructed azoospermia. Examination by confocal laser-scanning microscope of samples stained with PI and FITC-PSA or PI and FITC-Con A stain revealed viable and dead spermatozoa as well as viable and dead acrosome-reacted spermatozoa. In addition, fertility was evaluated from the distribution of spermatozoa in each area from the flow cytometry percentage. This method was shown previously to be useful for the evaluation of fertility as it demonstrated the presence of numerous spermatozoa in the fertile area of cases who did not succeeded in pregnancy. The hamster egg sperm penetration test yielded a fertility rate of 0-25% with a mean of 8.2±10.0%, which was significantly lower than the value of the normal group, but was not significantly different from the infertile group. The findings of this study indicated that the fertility of epididymal sperms is low, thereby pointing to the need for studies to improve the materials used in the artificial spermatocele as well as the method of sperm recovery. Furthermore, our findings suggest that flow cytometry may be used to select the epididymal sperms with the highest fertility for sperm recovery.

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Transitional cell carcinomas (TCC) in the human urinary bladder were observed on the fine morphological behaviour of the plasma membrane, with special references to the morphological differences in various grades of TCC utilizing thin sections and freeze fracture replicae electron microscopically. The purpose of this study is to clarify the characteristic differences between various grades of human TCC as a indicator suggestive of the TCC malignancy using electron microscopic techniques.
(1) The asymmetric unit membrane seen on the luminal membrane of the superficial cells was unique in all of TCC G1 an some TCC G2 cases. In other TCC G2 and TCC G3, there observed the symmetric unit membrane. Fusiform vesicles directly beneath the luminal plasma membrane were recognized only in TCC GI. (2) Microvilli (MV) seen on the luminal plasma membrane in TCC G1 were found to have the same appearance and distribution as on the normal bladder epithelium. As the grades increased in severity, there were less MV being shorter and club-likeforms. Even deformed with bleb formation microvilli were more apparentin TCC G3 cases than in TCC G2. (3) There was no difference observed between the junctional complex of the superficial cells of the all TCC grades and normal cells. As the cellular malignancies develop, however, the interdigitation structures and desmosomal appearances situated between neighboring intermediate cells tended to decrease. (4) Intracytoplasmic tonofilaments proliferation was obvious in TCC G2, but notin G3. (5) With increasing severity of TCC grades, intramembranous particles showed significant decrease in number as seen on freezefracture replicae.
In conclusion, these results suggest that fine structural observation may prove to be a usuful parameter to know the grades of TCC in human bladder tumors.

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We established LNCaP tumor in male nude mice after inoculation of LNCaP cells. The tumor produces the organ-specific glycoproteins in the human prostate, γ-seminoprotein (γ-Sm), which has been verified by immunohistochemistry and enzyme immuno assay. The LNCaP tumor is composed of 2 distinct portions, namely GEL/FLUID portion and SOLID portion. The GEL/FLUID portion contains much more γ-Sm than the SOLID portion does. The monoclonal antibody against γ-Sm (murine IgG₁, K) was radio-labeled with iodine-125 by lactoperoxidase method followed by passage over column chromatography. Finally the conjugates with specific activity of 49.8-56.6KBq/μg were obtained. Biodistribution of ¹²⁵I-labeled monoclonal antibody to γ-Sm (¹²⁵I-γMAb) was evaluated by whole-body autoradiography (ARG) and by determination of label uptake (DLU) by the LNCaP tumor using the well type gamma counter. The ARG were obtained 1-9 days after intravenous administrations of 32-38μg of ¹²⁵I-γMAb to 12 nude mice bearing LNCaP tumor. The DLU were evaluated 3, 4 and 7 days after intravenous administrations of 18-25μ/g of ¹²⁵I-γMAb to 9 nude mice bearing LNCaP tumor. The DLU by organs (GEL/FLUID portion, SOLID portion, liver, kidney, spleen, lung, etc.) were expressed as F-values (%) which were calculated by the following formula: F=radioactivity per gram of tissue (dpm/g)÷injected dose per gram of animal (dpm/g)×100 and tissue-to-blood ratios (T/B).
The specific uptake by the LNCaP tumors, especially in the GEL/FLUID portion, was observed on ARG, with optimal images of the tumor evaluated 4-7 days after administrations. The F-values and T/B of the LNCaP tumors were always higher than those of other organs. Especially T/B of GEL/FLUID portion were of 6.7 and 6.3, evaluated 4 and 7 days after administration of ¹²⁵I-γMAb respectively.
These results suggest that the radio-labeled γMAb is applicable for immunoscintigraphy of adenocarcinoma of the prostate.

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The subsets of tumor infiltrating lymphocytes (TILs) in 17 patients with renal cell carcinoma were studied by two-color flow cytometry and immunohistochemistry. In grade 1 tumors, CD4-positive cells were significantly increased compared to grade 2 and 3 tumors (35±7% vs 25±10%) (p<0.05). In 10 of 14 patients, CD8-positive cells were predominant over CD4-positive cells, resulting in less than one in CD4/CD8-ratio. Regarding CD4 cells in all 17 cases, the helper T-cells (CD4-positive and CD45RA-negative) were statistically predominant over the inducer T-cells (CD4-positive and CD45RA-positive) (p<0.01). When CD8 cells were investigated in 16 out of the 17 cases, the cytotoxic T-cells (CD8-positive and CD11b-negative) were found also significantly predominant over the suppressor T-cells (CD8-positive and CD11b-positive) (p<0.01).
Immunohistochemically, the infiltrating pattern of TILs in the 17 patients was classified into cluster (N=4), separate (N=6), and mixed types (N=7). The tumor in the cluster and mixed type had a tendency to be dominant in low grade tumors, and had the prominent CD8-positive cells (more than 90% were cytotoxic T-cells) over CD4-positive cells. However, no statistical significance was noted in this finding. The advanced tumor tended to show the single type of TIL infiltration. These results suggest that cytotoxic T-cells consisted of most of TILs in cluster and mixed types play an immunoreactive role against renal cell carcinoma.

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Gastrocystoplasty was undertaken for 5 patients with bladder dysfunction and incontinence caused by neurogenic bladder in 3 cases, bladder exstrophy in 1 case and trauma in 1 case respectively. The age of the patients ranged from 5 years through 14 years at the operation. Decreased renal function was recognized in 3 cases with neurogenic bladder before reconstruction. The other 2 cases had normal renal function.
Gastric segment was isolated with right gastroepiploic artery as a pedicle. Bladder was opened vertically and augmented with gastric segment. In 4 cases ureterogastrostomy with submucosal tunnel was performed in both sides. In neurogenic bladder cases, urethra was left without any surgical intervension, while other 2 cases underwent continent diversion using Mitrofanoff principle with urethra being closed.
Postoperative follow up period was 18 to 22 months. All cases had increased bladder volume and the dilatation of upper urinary tract disappeared or decreased in size in those who had upper urinary tract dilatation before operation. Urinary incontinence completely disappeared in continent diversion cases. In neurogenic bladder cases urinary leakage through urethra was negligible with 4 hour interval clean intermittent catheterization.
Laboratory examination showed no metablic derangement in blood gas analysis and electrolytes even in those who had decreased renal function. Blood urea nitrogen (BUN) and serum creatinine showed a little improvement or the same level as before. We didn't encounter any troubles in CIC such as the obstruction caused by mucus produced by gastric segment.
From our experience with those 5 pediatric cases underwent gastrocystoplasty, we thought gastric segment had some advantage as a tissue for augmentation cystoplasy compared with intestinal segment.

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Five patients with penile cancer were treated with radical radiotherapy combined with concurrent THP-ADM. No patient demonstrated distant metastasis, but three patients had regional nodes metastasis at first presentation. Delivered dose was 60Gy over 8-weeks and 10mg/m² of THP-ADM was administrated once a week during irradiation. Three of the five cases (60%) achieved complete response. Regarding the primary tumor complete response was noted in three cases (60%) and partial response in two (40%). Regarding the lymph nodes complete response was observed in two cases (67%) and no change in one. Histological effect upon the primary tumor was Grade IV in three cases and Grade JIB in two according to Obosi-Shimosato's criteria. That of the metastatic lymph nodes was Grade IV in one case. Three patients (60%) were alive with no evidence of disease with a median follow up of 27 months. Leukocytopenia and erosion of the penile skin were observed in all cases and meatal stenosis in one. All of these toxicities were acceptable. These results suggested that this combined therapy is effective for penile cancer and useful for the penispreserving treatment.

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The diagnostic significance of transrectal prostatic ultrasonography for chronic prostatitis and varicocele was evaluated in 380 male infertility patients.
Of 20 patients with pyospermia, thought to be mainly caused by chronic prostatitis, 10.0 percent showed heterogenous echo pattern of the prostate, while 25.0 percent showed capsular irregularity. Since 285 patients with non-infected semen showed similar sonographic findings, it is concluded that prostatic ultrasonography has little value in the diagnosis of chronic prostatitis in infertile patients.
Enlarged periprostatic echo-free zone, thought to coincide with the dilatation of the Santrini's plexus, was found in 42.9 and 42.7 percent of patients with chronic prostatitis and varicocele, respectively, in contrast to 34.0 percent of patients without either diseases. Twelve percent of patients with varicocele showed highly enlarged echo-free zone, which was significantly more frequent compared to 5.0 percent in normal patients. Moreover, follow up of 4 patients with varicocele pre- and post-operatively found 2 of them to show a great improvement in the enlargement of the zone. These results suggest that varicocele may cause the dilation of the Santrini's plexus through a venous anastomosis in some patients and transrectal ultrasonography may be a useful tool in detecting small varicoceles in such patients.

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We retrospectively studied clinical problems for 55 patients with primary hyperparathyroidism who were operated on at our hospital.
The chance to discovery of primary hyperparathyoidism and its accompanied symptoms were various. Other than classical symptoms, hypertension was noted in 12 patients and malignant tumors in 9. Forty-four percent of patients who had no bone related symptoms were found to have decreased bone mineral density (BMD). Even the patients with normal BMD were seen to increase the BMD, postoperatively. We thought that the parathyroidectomy was indicated for the asymptomatic patients with normal BMD. Biochemical investigation showed that positive rate were 50% for PTH-C, 94% for PTH-HS, 78% for intact PTH, 87% for serum total calcium and 98% for serum ionized calcium. Serum ionized calcium and intact PTH were useful for the diagnosis of patients who had normocalcemia or slight elevation of serum calcium.
The sensitivity was 61% for ultrasound sonography (US) and 49% for computer tomography (CT) and scintigram, respectively. The detection rate of US and CT was positively related to the size of the parathyroid glands, but scintigram was not.
The rate with which the parathyroid glands can be recognized during operation increased from 30% in the former group to 52% in the later group. As a result, 11% of the patients with adenoma had too much surgery and 29% of the patients with hyperplasia had too little surgery.

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Electrical field stimulation (EFS) induced a relaxation response in female rabbit urethral smooth muscle strips precontracted with phenylephrine. The relaxation response was inhibited by tetrodotoxin, but not by atropine, propranolol, or hexamethonium. Thus, the relaxation response results from stimulation of inhibitory non-adrenergic, non-cholinergic nerves. The EFS induced relaxation response was inhibited by an inhibitor of nitric oxide biosynthesis, N^G-nitro-L-arginine. This inhibition was overcome by addition of a precursor of nitric oxide, L-arginine. An inhibitor of soluble guanylate cyclase, methylene blue, but not an inhibitor of soluble adenylate cyclase, SQ22536 reduced the relaxation response. And a selective cyclic GMP phosphodiesterase inhibitor, M & B22948 and also a non selective phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine, potentiated the relaxation response. Cyclic GMP, but not cyclic AMP contents were significantly elevated by EFS in urethral smooth muscle strips. These data demonstrate that agents which affect the biosynthesis of nitric oxide are associated with the urethral relaxation evoked by EFS, and that cyclic GMP but not cyclic AMP mediates the relaxation response.

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From 1980 to 1990, we treated 45 patients with non-seminomatous germ cell tumors of greater than or equal to stage II according to the Japanese general rule for clinical and pathological studies on testicular tumors. The patients were divided into 2 groups based on the Indiana University Classification: 26 good risk patients (score≤6) and 19 poor risk patients (score≥7). The clinical results, the % dose intensity of Cisplatin and half-lives of tumor makers were analyzed in the two groups. The per cent dose intensity of Cisplatin of the induction chemotherapy was 61±24% in 1980-1985 and 87± 18% in 1986-1990. The NED rate improved from 66.7% (10/15) to 81.8% (9/11) in the good risk patients and from 33.3% (3/9) to 50.0% (5/10) in the poor risk patients between the above two periods. When the % dose intensity of Cisplatin exceeded 80%, the NED rate increased from 66.7% (10/15) to 90.0% (9/10) in good risk patients and from 33.3% (2/6) to 45.5% (5/11) in poor risk patients. The NED rate was only 25.0% (4/16) in the poor risk patients whose residual tumors were not resected. The half-lives of AFP and β-HCG from the latter part of the first course to the second course were 6.8±1.9 days and 4.4±1.4 days, respectively, in the patients with a good prognosis, while they were 6.5±1.5 days and 4.4±2.9 days, respectively, in with a poor prognosis. It was diffiult to assess the prognosis according to AFP and β-HCG half-life in the first course and its periodi determination is recommended to evaluate the response to chemotherapy.

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We investigated postoperative hydronephrosis in 50 patients (100 ureter) undergoing radical hysterectomy for uterine cervical cancer from Jan. 1989 to Dec. 1991 at Department of Obstetrics and Gynecology in Nagasaki University Hospital.
The incidence of hydronephrosis was 68.1% of patients, and hydronephrosis was seen significantly more frequently and was of a higher grade on the right kidney than the left. After one year, hydronephrosis disappeared in 59.1% of patients (65.1% of right kidney, 88.2% of left kidney), and only 2 of 93 kidney have worsened.
In cases without hydronephrosis, hydronephrosis developed in only 3 of 31 kidney after one year due to local recurrence or nodule metastasis of the original disease.
We compared therapeutic effects of 3 methods (ureteral stent, PNS, no treatment). But there was no significant difference between these methods, we could not determine which was the best treatment. And we observed that indwelling ureteral stent might interrupt spontaneous healing of ureter.
Radiotherapy didn't significant influence hydronephrosis after radical hysterectomy;
Therefore, we suggest that, in patients with hydronephrosis without other severe urological complications after radical hysterectomy, clinical course should be observated for at least one year, first and them some treatments should be applied if cases worsen gradually than before.

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To evaluate the condition of incontinence in patients with senile dementia, we performed computed tomography X-rays to the brain and analyzed the relationship among the circulatory defect of the brain, the brain atrophy and the degree of incontinence. There were 92 patients subjected to this study who were hospitalised due to senile dementia; 74 patients had vascular dementia, 10 patients had senile dementia of Alzheimer type, and 8 patients had the mixed type. (age ranged: 54-95 years; mean: 80.3 years). The degree of incontinence in these patients varied as follows: 18 patients with continence, 16 patients with moderate incontinence, 58 patients with total incontinence. The diagnosis of circulatory defect of the brain was based on computed tomography observation of periventricular lucency (P. V. L.), and the degree of brain atrophy was evaluated based on 4 criteria: the Lateral body ratio, the Huckman number, the Evans ratio, and the enlargement of the subarachnoid space.
Among the 92 patients, P. V. L. was present in 31 patients, among them 27 patients suffered from incontinence. There was a significant correlation between P. V. L. and incontinence (p<0.001). As the incontinence progressively worsened (Continence, Moderate incontinence Total incontinence), the lateral body ratio increased to 24.8, 27.8, 28.6, (p<0.05). The Huckman number also increased to 18.3, 19.3, 21.3, (p<0.01), and the evans ratio likewise 29.9, 32.3, 33.7 (p<0.01). The enlargement of the subarachnoid space was also correlated with the severity of incontinence.
We conclude that urinary incontinence originating from senile dememtia is connected to brain atrophy and is strongly influenced by the circulatory disorders of the brain.

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A DNA ploidy pattern of prostatic adenocarcinoma was studied by flow cytometry using the formalin-fixed, paraffin-embedded tissues obtained from 65 patients. These patients received hormone therapy preoperatively. Forty cases (61.5%) showed a diploid pattern, and 25 (38.5%) an aneuploid pattern.
Comparing this ploidy pattern with histological classification, the aneuploid pattern was found in 13 cases (52%) of poorly differentiated group, 12 cases (48.0%) of moderately differentiated group and 0 case (0%) of well differentiated group. Thus, rate of aneuploid pattern increased with an increase in the grade of malignancy.
Five years survival rate was 62.6% in the diploid group while it decreased to 30.9% in the aneuploid group. There was a significant difference between the two groups. In 23 cases with stage D, the ploidy pattern of primary region could be compared with that of metastatic region (lymph nodes). The prognosis of patients who exhibited the aneuploid pattern in metastatic region was significantly worse than that of other patients.
These data suggested that flow cytometric DNA analysis of prostatic cancer materials after hormone therapy also produces meaningful information in predicting the prognosis of prostatic cancer.

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A 24-year-old man presented with right scrotal swelling and was diagnosed as having a testicular cancer. A high inguinal orchiectomy was carried out. Histological examination revealed immature teratoma and yolk sac tumor of the testis. Eight months later, 2 separate metastatic lesions appeared in the lungs, both of which were removed by operation after a course of combination chemotherapy with Etoposide and Cisplatin. The histology showed one to be composed of immature teratoma, and the another of yolk sac tumor.

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Since 1989, 4 patients with Stage III nonseminomatous germ cell tumor of the testis underwent thoracotomy for persistent radiographic masses after systemic chemotherapy. They were treated with multi-drug regimen including cisplatin, vincristine, methotrexate, peplomycin, and etoposide until normalization of tumor markers was obtained. Residual masses of the 4 patients consised of viable cancer cells in 1 patient, immature teratoma in 1, mature teratoma in 1 and necrosis in 1.
Of the 4 patients 3 achieved complete remission and are doing well with no evidence of disease, while the other case with residual viable cancer cells died of renal failure.
The key to successful treatment of advanced testicular cancer was considered to be a favorable response to chemotherapy and complete resection of any residual tumors.

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We treated a 25-year-old hemophilia A patient (FVIII:C activity 2%) with left ureteral stone by means of extracorporeal shock wave lithotripsy under replacement therapy of concentrated Factor VIII material.
The patient was attacked by sudden onset of left renal colic with gross hematuria on the 12th postoperative day. Renal ultrasonography and computed tomography demonstrated subcapsular bleeding of the left kidney. In spite of usual antihemophiliac replacement therapy, bleeding was extended from the retroperitoneal space to intraperitoneal and intrapleural space because potent Factor VIII inhibitors (14 Bethesda Unit) was produced. After embolization of the left renal artery, double filtration plasmapheresis and bypassing therapy using prothrombin complex concentrate were performed effectively to save the patient's life.

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