We discussed in this paper on the relation of measurable pathological characteristics of the primary bladder cancer to the prognosis with materials obtained from 200 cases in our clinic during the period from 1958 to 1968.
1) In relation of Ookita's classification (P, S, W, I-type) to 5-year-survival rate, P-type was most frequent and 84.2%, in 143 patients, but there were no differences among P, S and W-types in 5-year-survival rate.
2) In relation of Broders' classification to 5-year-survival rate, grade I was 86.5% in 84 patients and grade II, 88.9% in 76 patients.
Between grade I and grade II, there was no significant difference in survival rate, but among grade I, II and grade III or grade IV, and between grade III and grade IV, significant difference was obtained.
3) In relation of Yamada's classification to survival rate, group I was similar to P-type and grade I-II. The number of group II was too small for statistical treatment.
4) In comparison of the survival rates with regard to the sex, it was almost the same: 72.4% in male and 70.1% in female.
5) In comparison of various age group, there was no significant difference in 5-year-survival rate.
6) The infiltrated groups to lymph or blood vessels indicated a lower survival rate than patients without infiltration.

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Nucleic acid metabolism was studied to observe the metabolic activities of bladder tumors. Surgically obtained specimens were subjected to this study. Radio-active nucleic acid precursors; C¹⁴-formate, which was incorporated into nucleic acids via de novo synthetic pathway, and C¹⁴-8-adenine, which was also incorporated via salvage pathway, were used. These radio-active substances were incorporated into nucleic acids, so that the incorporation rates were expressed as relative specific activities. The results were as follows:
1. C¹⁴-formate incorporation was higher in grade 2, 3, and 4 of bladder tumors than in the control. Also it was highest in stage B2 bladder tumors. Among the purine bases RSA of thymine was the highest. There were no great differences between the other purines and pyrimidines.
2. C¹⁴-8-adenine was also incorporated into nucleic acid bases of the bladder tumors. It was assumed that the higher the grades and stages, the higher the incorporation rates. It was considered that in bladder tumors there was salvage pathway, which had not been described in the literatures.
3. Comparison between de novo synthesis and salvage pathway; Concerning the incorporation rates, salvage pathway was more active than de novo synthesis in bladder tumors.

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Energy metabolism was studied on the specimens of the bladder tumors obtained at operations.
Tissue respiration, aerobic and anerobic glycolysis were determined by Warburg's manometric method. Adenosine nucleotides were also analysed by Bucher's method. Inorganic phosphorus contents were determined by Martin-Doty's method. Energy charge was calculated as to the principal adovocated by Atkinson.
The results were as follows:
1. Anerobic glycolysis was remarkably high in the bladder tumors, although tissue respiration and aerobic glycolysis were activated.
2. Warburg's quotient of the bladder tumors was high, which was in good agreement with the results reported for the other malignancies.
3. Meyerhof's quotient was found to be high in badder tumors. In addition there existed Pasteur effect. It was assumed that in this malignancy there existed glycolytic inhibition by oxygen or aerobic condition, which had been demonstrated in normal tissues. Therfore, it was considered that there were no great differences between bladder tumors and normal tissues as to the qualities of the respiration and glycolysis.
4. Among the adenosine nucleotides, contents of ATP and ADP were elevated in bladder tumors with progressive increase of inorganic phosphorus. Accordingly total adenosine nucleotides were increased as the grades of the tumors progressed.
5. It was demonstrated that the bladder tumors had high level of energy charge.
6. It was considered that mainly anerobic glycolysis would produce high energy charge, which seemed to be the source of proliferation of this malignancy.

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In the previous study, the re-construction of normal vaginal flora which was made up with artificial colonization of cultured viable Lactobacilli, was proved to be effective in preventing the recurrent urinary tract infection, and then it was clarified that the acquired ill disposition, easily falling in recurrent urinary infection, in preclimacteric females resulted from the establishment of pathogenic bacterial flora on their vaginal mucosa.
The procedure, the colonization of viable Lactobacilli on vaginal mucosa, had resulted in some 80 to 90% effectiveness in preventing the recurrent urinary infection for from 14 to 34 months' period in each of 17 cases successfully tried out. There were 9 cases out of them, who were without the persistence of Lactobacilli from their vagina in the above-mentioned follow up/or and further 12 months' periods, and their fates for urinary tract infection were as followings,
a) 2 cases had re-acquired the ill disposition,
b) 2 cases had entirely been free from the urinary tract infection for 46 and 38 months respectively since the completion of the procedure,
c) 4 cases had suffered from one or 2 single episode infections through the follow-up period from 24 to 38 months,
d) the last one case had been free from infection in the first 20 months, and then suffered 2 infections in the last 6 months through her 37 months' follow up period, and the effectiveness of the procedure was suspended.
The well being 4 cases out of 6 (b+c), had carried uniformly some coryneform Gram negative small rods in their vaginal flora as predominant organism, and one case out of the remaining 2 cases carried a few numbers of Esch. coli, and the last case (d) had also carried a Gram negative small rod, which was identified as Haemophilus parainfluenzae, in recent 9 months as a predominant organism.
For the hope of discovering some predominant organisms which did not cause any urinary infections instead of Lactobacilli which were supposed to be missing in the postmenopausal stage, we surveyed about the normal vaginal bacteria above all the predominant ones in 40 normal females who visited our gynecological clinic for the cytological examination of cancer. They were 32 to 62 years of age and more than 60% of them were in the 5th decade. The vaginal pool secretions were subjected to cytological and bacteriological examinations and also pH of the secretions were determined by a paper method using Brom cresol green as an indicator.
The results of the survey suggested that, in “normal” females the predominant organisms in vaginal bacterial flora were only consisted from Lactobacilli and some Gram negative small rods, presumably so-called Haemophilus vaginalis (Gardner & Dukes, 1955), and their predominacies in vaginal flora changed from the former to the latter alternately correlating with the ovarian activities representative of premenopausal and postmenopausal situations, and then the latter gradually disappeared with aging of the hosts.
For the last condition of vaginal mucosa, we called temporarily “scanty material stage” of vaginal mucosa, and took the condition which was also represented as carrying scanty vaginal secretion or/and only a few cell and bacterial components, for showing a consumed circumstance for bacterial growth, even if there were any urinary pathogens, did not permit them sufficient growth enough to initiate some infective diseases.
Out of our patients, subjected to the procedure, and missing the Lactobacilli thereafter, and not yet having any re-acquistions of the ill disposition, there were some who had the coryneform Gram negative small rod as predominant organism in their vaginal flora, and there was one who had only a few numbers of Esch. coli as an inhabitant persisted.

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The authors have examined levels of and changes in serum haptoglobin in 33 cases with renal cell carcinoma. Immunoelectrophoresis and the single radial immunodiffusion method were used to clarify the ability of serum haptoglobin to detect the said carcinoma.
Results obtained were as follows:
1) The mean with standard deviation of concentration of serum haptoglobin from the 33 cases was 317±199mg/dl, 28 were above the normal mean. A remarkable rise in haptoglobin level was found in patients with advanced cancer.
2) Haptoglobin phenotypes in the immunoelectrophoretic patterns were: 4 cases of Hp1-1, 9 cases of Hp2-1 and 17 cases of Hp2-2. Serum haptoglobin phenotype distribution was normal. The mean serum haptoglobin concentration with standard deviation in each phenotype was 402±219mg/dl. in Hp2-2, 376±163mg/dl, in Hp2-1 and 230±114mg/dl. in Hp1-1.
3) A close relationship was found to exist between α₂-globulin and serum haptoglobin. Increases in α₂-globulin in renal cell carcinoma resulted from increases in haptoglobin. In a few cases, however, no increases in α₂-globulin occurred despite an increase in haptoglobin.
4) The levels and changes in ceruloplasmin, α₂-macroglobulin and α₂-HS glycoprotein in the α₂-fraction were determined simultaneously with those of haptoglobin. The mean and standard deviation of ceruloplasmin was 36±12mg/dl; that of α₂-macroglobulin was 189±50mg/dl, while that of α₂-HS glycoprotein was 46±13mg/dl. Increases in ceruloplasmin and decreases in α₂HS and α₂M were observed in patients with advanced cancer.
5) Serum haptoglobin levels showed a definite increase in renal cell carcinoma in comparison with various other urological disorders.
6) A remarkable increase in serum haptoglobin was found in patients with fever, raised ESR, anemia and CRP positive. In patients without these symptoms, on the other hand, haptoglobin showed only a slight increase. No correlations were found between haptoglobin and white blood cells, between haptoglobin and cell types, or between haptoglobin and liver functions.
7) There was a definite correlation between serum haptoglobin and staging, and also between haptoglobin and survival rate. Patients with localized renal tumors had normal serum haptoglobin levels and experienced slight increases in haptoglobin. Patients with renal capsule invasion experienced a remarkable increase in haptogloibn. Patients with demonstrable distant metastasis exhibited abnormally elevated haptoglobin levels.
8) Prognosis was generally poor in patients with elevated haptoglobin levels. Patients with metastasis showing definite increases in haptoglobin had very poor prognoses.
9) Patients in good postoperative clinical condition exhibited normal serum haptoglobin levels. Elevated serum haptoglobin levels were noted in patients whose clinical evidence betrayed recurrence.
Serum haptoglobin may be helpful in early detection of renal cell carcinoma recurrence in patients who have been operated upon. Serum haptoglobin increased somewhat, particularly in those patients with renal cell carcinoma and helped us to define the state of the said carcinoma. It is concluded that the determination of serum haptoglobin has a practical use in the evaluation of clinical conditions, in preoperative staging, in prognosis and in the detection of metastasis.

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The mechanism of primary vesicoureteral reflux had been investigated by many authors, such as Sampson, Grüber, Stephens, Tanagho and Hutch etc. Recent studies have demonstrated that primary defect for protection of the reflux possibly exists in the trigonal function or intravesical ureter itself rather than the disturbance of the passive flap valve mechanism.
In the view points that antireflux operations such as Paquins method which disconnect the trigone and intravesical ureter anatomically and functionally have been in success clinically, the primary factor of the primary reflux might exist in intravesival ureter. For the purpose of confirmation whether the intravesical ureter and the primary vesicoureteral reflux correlate to each other, two studies were performed.
1) Serial radiographic observation of the bladder in which two silver clips were placed at the vesical serosal sides of the orifice and the new ureterovesical joint during the Politano-Leadbetter's reim-plantation was done through the full to the empty.
The results were that although the trigone did not become shorter as with the normal at the time of status change from the full to the voiding, the intravesical length of the ureter, which was indicated by the two silver clips, was doubled with complete protection of reflux through this procedure.
2) Pathohistological studies of the intravesical ureters (intramuscular and submucosal ureters) including the orifice that were obtained at the time of operations were performed with cross or logitudinal sections in 22 ureters of 16 cases (adult, 12 ureters of 7 cases and child, 10 ureters of 9 cases) and 9 ureters as normal controls with H. E., Azan Mallory, PTAH, Heidenhain's ion hematoxylin and elastics van Gieson's stains.
The results were as follow; all of normal intravesical ureters showed thick longitudinal muscle fibers extended to a submucosa of an orifice. On the other hand the ureters with reflux showed fibrosis (6 ureters), hypoplasia (9 ureters) and abnormal orientation (4 ureters) of the ureteral musculature with markedly increased connective tissues.
From the results of these the normal or nonrefluxing intravesical ureters have elasticity and muscular tension to adapt to the change of vesical capacity or intravesical pressure. Compaired with this it is suspected that the intravesical ureters in primary reflux are in failure of this mechanism like a none elastic rubber tube because of the muscular abnormality and increased fibrous or elastic tisses. Namely this elastic and adaptable intravesical ureteral form will be minimal requirement for an antireflux mechanism although a trigonal function or intravesical ureteral length are important factors. Therefore, in primary reflux, the original intravesical ureter should not be used in ureterovesicoplasty.
Also we presented the cases concerning pathohistological forms of the intravesical ureters, intravesical ureteral length and position of an orifice etc. as showing Table 1 and discussed about the personal difference of antirefluxing ability.
The other interesting finding was a hollow at the ureterovesical junction during the voiding phase in cases of primary reflux as demonstrated in Figs. 18 and 19. It suggests that this hollow makes proof of the none elastic intravesical ureter in primary vesicoureteral reflux and is useful to determine whether the therapy should be operative or conservative.

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Isoantigens A, B and H(O) identical with those present in erythrocyte are also found in various normal tissues, the majority of which are derived from entodermal origin. Previous investigators suggested that the blood group substances are affected by cancerous transformation. Although immunofluorescence technique has been commonly used for demonstration of the isoantigens, the specific red cell adherence test (SRCA), a modified Coombs' mixed cell agglutination technique, can be employed for the same purpose.
Paraffin-embedded tissue sections obtained from 20 cases of urothelial tumors including 18 bladder carcinomas, a ureteral carcinoma and a leukoplakia of the bladder were submitted to SRCA. The isoantigens were clearly detected in the non-neoplastic urothelium in all cases as well as in the leukoplakia. In the neoplastic lesions, however, the isoantigens were found to be totally or partially disappeared, indicating immunological dedifferentiation. It was considered that loss of the isoantigens was closely related to cancerous transformation from pathological, ontogenic and immunochemical aspects.
SRCA is a reproducible, sensitive and technically easy immunohistological technique, and expected to furnish fruitful informations on cancer research.

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A pattern of proliferation in compensatory renal hypertrophy in rats was studied using ³H-thymidine autoradiography.
The results obtained were as follows:
1) The cell proliferation in compensatory renal hypertrophy was most marked in the outer cortex especially in proximal convoluted tubule cells.
2) The number of labelled cells began to increase 24 hours after contralateral nephrectomy, reached a maximum value between 48 and 72 hours and returned to the control value after 2 weeks.
3) The ratio of the labelling in interstitial cells to tubule cells was constant throughout the period.

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